Bibliographic database

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Authors: Type:

2017

  • S. Choi, C. Cui, Y. Luo, S. Kim, J. Ko, X. Huo, J. Ma, L. Fu, R. F. Souza, I. Korichneva, and Z. Pan, “Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through orai1,” The faseb journal, p. fj.201700227RRR+, 2017. doi:10.1096/fj.201700227rrr
    [Abstract]

    Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca2+ entry ({SOCE}) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma ({ESCC}) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human {ESCC} cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of {ESCC} cell lines and that the effect of zinc is reversible with {N,N},{N′,N}′-Tetrakis (2-pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas nontumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1-mediated {SOCE} and on intracellular Ca2+ oscillations in the {ESCC} cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both {SOCE} and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1-mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc-induced cancer prevention and {Orai1-SOCE} signaling pathway in cancer {cells.—Choi}, S., Cui, C., Luo, Y., Kim, {S.-H}., Ko, {J.-K}., Huo, X., Ma, J., Fu, {L.-W}., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.

    @article{citeulike:14444652,
    abstract = {Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca2+ entry ({SOCE}) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma ({ESCC}) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human {ESCC} cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of {ESCC} cell lines and that the effect of zinc is reversible with {N,N},{N′,N}′-Tetrakis (2-pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas nontumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1-mediated {SOCE} and on intracellular Ca2+ oscillations in the {ESCC} cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both {SOCE} and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1-mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc-induced cancer prevention and {Orai1-SOCE} signaling pathway in cancer {cells.—Choi}, S., Cui, C., Luo, Y., Kim, {S.-H}., Ko, {J.-K}., Huo, X., Ma, J., Fu, {L.-W}., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.},
    author = {Choi, Sangyong and Cui, Chaochu and Luo, Yanhong and Kim, Sun-Hee and Ko, Jae-Kyun and Huo, Xiaofang and Ma, Jianjie and Fu, Li-wu and Souza, Rhonda F. and Korichneva, Irina and Pan, Zui},
    citeulike-article-id = {14444652},
    citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.201700227rrr},
    citeulike-linkout-1 = {http://www.fasebj.org/content/early/2017/09/14/fj.201700227RRR.abstract},
    citeulike-linkout-2 = {http://www.fasebj.org/content/early/2017/09/14/fj.201700227RRR.full.pdf},
    citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/28928244},
    citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=28928244},
    day = {19},
    doi = {10.1096/fj.201700227rrr},
    issn = {1530-6860},
    journal = {The FASEB Journal},
    month = sep,
    pages = {fj.201700227RRR+},
    pmid = {28928244},
    posted-at = {2017-10-03 15:35:30},
    priority = {2},
    publisher = {Federation of American Societies for Experimental Biology},
    title = {Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1},
    url = {http://dx.doi.org/10.1096/fj.201700227rrr},
    year = {2017}
    }

  • B. Montalbán, S. Thijs, Mª. C. Lobo, N. Weyens, M. Ameloot, J. Vangronsveld, and A. Pérez-Sanz, “Cultivar and Metal-Specific effects of endophytic bacteria in helianthus tuberosus exposed to cd and zn,” International journal of molecular sciences, vol. 18, iss. 10, p. 2026+, 2017. doi:10.3390/ijms18102026
    [Abstract]

    Plant growth promoting endophytic bacteria ({PGPB}) isolated from Brassica napus were inoculated in two cultivars of Helianthus tuberosus ({VR} and D19) growing on sand supplemented with 0.1 {mM} Cd or 1 {mM} Zn. Plant growth, concentrations of metals and thiobarbituric acid ({TBA}) reactive compounds were determined. Colonization of roots of H. tuberosus D19 by Pseudomonas sp. 262 was evaluated using confocal laser scanning microscopy. Pseudomonas sp. 228, Serratia sp. 246 and Pseudomonas sp. 262 significantly enhanced growth of H. tuberosus D19 exposed to Cd or Zn. Pseudomonas sp. 228 significantly increased Cd concentrations in roots. Serratia sp. 246, and Pseudomonas sp. 256 and 228 resulted in significantly decreased contents of {TBA} reactive compounds in roots of Zn exposed D19 plants. Growth improvement and decrease of metal-induced stress were more pronounced in D19 than in {VR}. Pseudomonas sp. 262-green fluorescent protein ({GFP}) colonized the root epidermis/exodermis and also inside root hairs, indicating that an endophytic interaction was established. H. tuberosus D19 inoculated with Pseudomonas sp. 228, Serratia sp. 246 and Pseudomonas sp. 262 holds promise for sustainable biomass production in combination with phytoremediation on Cd and Zn contaminated soils.

    @article{citeulike:14444650,
    abstract = {Plant growth promoting endophytic bacteria ({PGPB}) isolated from Brassica napus were inoculated in two cultivars of Helianthus tuberosus ({VR} and D19) growing on sand supplemented with 0.1 {mM} Cd or 1 {mM} Zn. Plant growth, concentrations of metals and thiobarbituric acid ({TBA}) reactive compounds were determined. Colonization of roots of H. tuberosus D19 by Pseudomonas sp. 262 was evaluated using confocal laser scanning microscopy. Pseudomonas sp. 228, Serratia sp. 246 and Pseudomonas sp. 262 significantly enhanced growth of H. tuberosus D19 exposed to Cd or Zn. Pseudomonas sp. 228 significantly increased Cd concentrations in roots. Serratia sp. 246, and Pseudomonas sp. 256 and 228 resulted in significantly decreased contents of {TBA} reactive compounds in roots of Zn exposed D19 plants. Growth improvement and decrease of metal-induced stress were more pronounced in D19 than in {VR}. Pseudomonas sp. 262-green fluorescent protein ({GFP}) colonized the root epidermis/exodermis and also inside root hairs, indicating that an endophytic interaction was established. H. tuberosus D19 inoculated with Pseudomonas sp. 228, Serratia sp. 246 and Pseudomonas sp. 262 holds promise for sustainable biomass production in combination with phytoremediation on Cd and Zn contaminated soils.},
    author = {Montalb\'{a}n, Blanca and Thijs, Sofie and Lobo, Mª C. and Weyens, Nele and Ameloot, Marcel and Vangronsveld, Jaco and P\'{e}rez-Sanz, Araceli},
    citeulike-article-id = {14444650},
    citeulike-linkout-0 = {http://dx.doi.org/10.3390/ijms18102026},
    citeulike-linkout-1 = {http://www.mdpi.com/1422-0067/18/10/2026},
    citeulike-linkout-2 = {http://www.mdpi.com/1422-0067/18/10/2026/pdf},
    day = {21},
    doi = {10.3390/ijms18102026},
    journal = {International Journal of Molecular Sciences},
    month = sep,
    number = {10},
    pages = {2026+},
    posted-at = {2017-10-03 15:34:35},
    priority = {2},
    title = {Cultivar and {Metal-Specific} Effects of Endophytic Bacteria in Helianthus tuberosus Exposed to Cd and Zn},
    url = {http://dx.doi.org/10.3390/ijms18102026},
    volume = {18},
    year = {2017}
    }

  • Y. Olgar, S. Ozdemir, and B. Turan, “Induction of endoplasmic reticulum stress and changes in expression levels of zn2+-transporters in hypertrophic rat heart,” Molecular and cellular biochemistry, 2017. doi:10.1007/s11010-017-3168-9
    @article{citeulike:14426288,
    author = {Olgar, Yusuf and Ozdemir, Semir and Turan, Belma},
    citeulike-article-id = {14426288},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s11010-017-3168-9},
    day = {28},
    doi = {10.1007/s11010-017-3168-9},
    issn = {0300-8177},
    journal = {Molecular and Cellular Biochemistry},
    month = aug,
    posted-at = {2017-09-06 13:50:14},
    priority = {2},
    title = {Induction of endoplasmic reticulum stress and changes in expression levels of Zn2+-transporters in hypertrophic rat heart},
    url = {http://dx.doi.org/10.1007/s11010-017-3168-9},
    year = {2017}
    }

  • A. Kocy{l}a, A. Pomorski, and A. Krężel, “Molar absorption coefficients and stability constants of zincon metal complexes for determination of metal ions and bioinorganic applications,” Journal of inorganic biochemistry, vol. 176, pp. 53-65, 2017. doi:10.1016/j.jinorgbio.2017.08.006
    @article{citeulike:14426286,
    author = {Kocy{\l}a, Anna and Pomorski, Adam and Krę\.{z}el, Artur},
    citeulike-article-id = {14426286},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jinorgbio.2017.08.006},
    doi = {10.1016/j.jinorgbio.2017.08.006},
    issn = {01620134},
    journal = {Journal of Inorganic Biochemistry},
    month = nov,
    pages = {53--65},
    posted-at = {2017-09-06 13:49:11},
    priority = {2},
    title = {Molar absorption coefficients and stability constants of Zincon metal complexes for determination of metal ions and bioinorganic applications},
    url = {http://dx.doi.org/10.1016/j.jinorgbio.2017.08.006},
    volume = {176},
    year = {2017}
    }

  • H. Mehdi, W. Gong, H. Guo, M. Watkinson, H. Ma, A. Wajahat, and G. Ning, “Aggregation-Induced emission (AIE) fluorophore exhibits a highly ratiometric fluorescent response to zn(2+) in vitro and in human liver cancer cells.,” Chemistry (weinheim an der bergstrasse, germany), 2017.
    [Abstract]

    Two novel organic fluorophores, containing bis-naphthylamide and quinoline motifs, have been designed and synthesized. One of the fluorophores contains an isobutylene unit and exhibits a significant aggregation-induced emission ({AIE}) and a remarkable highly selective ratiometric fluorescence response towards Zn(2+) in solution as well as in human liver cancer cells. The {AIE} behavior of this fluorophore was fully verified by fluorescence and {UV}/Vis spectroscopy, quantum yield calculations, and single-crystal X-ray diffraction, which revealed an intricate crystal packing system. Conversely, a fluorophore that lacks the isobutylene moiety did not exhibit any significant fluorescent properties as a result of its more flexible molecular structure that presumably allows free intramolecular rotational processes to occur. {\copyright} 2017 {Wiley-VCH} Verlag {GmbH} & Co. {KGaA}, Weinheim.

    @article{citeulike:14412935,
    abstract = {Two novel organic fluorophores, containing bis-naphthylamide and quinoline motifs, have been designed and synthesized. One of the fluorophores contains an isobutylene unit and exhibits a significant aggregation-induced emission ({AIE}) and a remarkable highly selective ratiometric fluorescence response towards Zn(2+) in solution as well as in human liver cancer cells. The {AIE} behavior of this fluorophore was fully verified by fluorescence and {UV}/Vis spectroscopy, quantum yield calculations, and single-crystal X-ray diffraction, which revealed an intricate crystal packing system. Conversely, a fluorophore that lacks the isobutylene moiety did not exhibit any significant fluorescent properties as a result of its more flexible molecular structure that presumably allows free intramolecular rotational processes to occur. {\copyright} 2017 {Wiley-VCH} Verlag {GmbH} \& Co. {KGaA}, Weinheim.},
    author = {Mehdi, Hassan and Gong, Weitao and Guo, Huimin and Watkinson, Michael and Ma, Hua and Wajahat, Ali and Ning, Guiling},
    citeulike-article-id = {14412935},
    citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/28612518},
    citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=28612518},
    day = {14},
    issn = {1521-3765},
    journal = {Chemistry (Weinheim an der Bergstrasse, Germany)},
    month = jun,
    pmid = {28612518},
    posted-at = {2017-08-11 17:58:11},
    priority = {2},
    title = {{Aggregation-Induced} Emission ({AIE}) Fluorophore Exhibits a Highly Ratiometric Fluorescent Response to Zn(2+) in vitro and in Human Liver Cancer Cells.},
    url = {http://view.ncbi.nlm.nih.gov/pubmed/28612518},
    year = {2017}
    }

  • L. Dierichs, V. Kloubert, and L. Rink, “Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages.,” European journal of nutrition, 2017.
    [Abstract]

    Polarization of macrophages by environmental stimuli leads to the characteristic of different phenotypes that exhibit distinct functions, ranging in a continuous spectrum from pro-inflammatory M1 up to immunoregulatory and wound-healing M2 macrophages. Diseases like cancer, allergic asthma or diabetes are associated with an {M1/M2} imbalance. Owing to the importance of the essential trace element zinc for the immune system and its involvement in signal transduction as a second messenger, we investigated the impact of zinc on M1 and M2 polarization of macrophages in vitro. A polarization model with human {THP}-1 cells was established and validated with previously described markers using quantitative real-time {PCR}, Western blot and flow cytometry. Intracellular free Zn(2+) was determined with {FluoZin}-{3-AM}. Whereas {pSTAT1} and {HLA}-{DR} or {pSTAT6} and Dectin-1 distinguish between M1 and M2 macrophages, respectively, {CD86} and {CD206} failed. Depending on the used markers, both zinc supplementation in physiological dose (50 {µM}) and zinc deficiency promote M1 polarization of {THP}-1-derived macrophages. Furthermore, zinc supplementation strongly inhibits M2 polarization. For the first time, we show a modulating effect of zinc for the polarization of human macrophages. The strong inhibitory effect of zinc supplementation on M2 polarization indicates a relevance regarding M2-dominated diseases like allergic asthma or cancer. All in all, zinc achieves a great potential for modulating macrophage polarization.

    @article{citeulike:14412934,
    abstract = {Polarization of macrophages by environmental stimuli leads to the characteristic of different phenotypes that exhibit distinct functions, ranging in a continuous spectrum from pro-inflammatory M1 up to immunoregulatory and wound-healing M2 macrophages. Diseases like cancer, allergic asthma or diabetes are associated with an {M1/M2} imbalance. Owing to the importance of the essential trace element zinc for the immune system and its involvement in signal transduction as a second messenger, we investigated the impact of zinc on M1 and M2 polarization of macrophages in vitro. A polarization model with human {THP}-1 cells was established and validated with previously described markers using quantitative real-time {PCR}, Western blot and flow cytometry. Intracellular free Zn(2+) was determined with {FluoZin}-{3-AM}. Whereas {pSTAT1} and {HLA}-{DR} or {pSTAT6} and Dectin-1 distinguish between M1 and M2 macrophages, respectively, {CD86} and {CD206} failed. Depending on the used markers, both zinc supplementation in physiological dose (50 {µM}) and zinc deficiency promote M1 polarization of {THP}-1-derived macrophages. Furthermore, zinc supplementation strongly inhibits M2 polarization. For the first time, we show a modulating effect of zinc for the polarization of human macrophages. The strong inhibitory effect of zinc supplementation on M2 polarization indicates a relevance regarding M2-dominated diseases like allergic asthma or cancer. All in all, zinc achieves a great potential for modulating macrophage polarization.},
    author = {Dierichs, Laura and Kloubert, Veronika and Rink, Lothar},
    citeulike-article-id = {14412934},
    citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/28687933},
    citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=28687933},
    day = {07},
    issn = {1436-6215},
    journal = {European journal of nutrition},
    month = jul,
    pmid = {28687933},
    posted-at = {2017-08-11 17:57:38},
    priority = {2},
    title = {Cellular zinc homeostasis modulates polarization of {THP}-1-derived macrophages.},
    url = {http://view.ncbi.nlm.nih.gov/pubmed/28687933},
    year = {2017}
    }

  • A. Krężel and W. Maret, “The functions of metamorphic metallothioneins in zinc and copper metabolism.,” International journal of molecular sciences, vol. 18, iss. 6, 2017.
    [Abstract]

    Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins ({MTs}) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn(2+) ions at picomolar concentrations, extensive subcellular re-distribution of Zn(2+), the loading of exocytotic vesicles with zinc species, and the control of Zn(2+) ion signalling. In parallel, characteristic features of human {MTs} became known: their graded affinities for Zn(2+) and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian {MTs} describe with a set of seven divalent or eight to twelve monovalent metal ions, {MTs} are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian {MTs} should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of {MTs} with Zn(2+) and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. {MT} represents a unique biological principle for buffering the most competitive essential metal ions Zn(2+) and Cu⁺. How this knowledge translates to the function of other families of {MTs} awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

    @article{citeulike:14412931,
    abstract = {Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins ({MTs}) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn(2+) ions at picomolar concentrations, extensive subcellular re-distribution of Zn(2+), the loading of exocytotic vesicles with zinc species, and the control of Zn(2+) ion signalling. In parallel, characteristic features of human {MTs} became known: their graded affinities for Zn(2+) and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian {MTs} describe with a set of seven divalent or eight to twelve monovalent metal ions, {MTs} are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian {MTs} should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of {MTs} with Zn(2+) and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. {MT} represents a unique biological principle for buffering the most competitive essential metal ions Zn(2+) and Cu⁺. How this knowledge translates to the function of other families of {MTs} awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.},
    author = {Krę\.{z}el, Artur and Maret, Wolfgang},
    citeulike-article-id = {14412931},
    citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/28598392},
    citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=28598392},
    day = {09},
    issn = {1422-0067},
    journal = {International journal of molecular sciences},
    month = jun,
    number = {6},
    pmid = {28598392},
    posted-at = {2017-08-11 17:57:06},
    priority = {2},
    title = {The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism.},
    url = {http://view.ncbi.nlm.nih.gov/pubmed/28598392},
    volume = {18},
    year = {2017}
    }

  • N. Z. Z. Gammoh and L. Rink, “Zinc in infection and inflammation.,” Nutrients, vol. 9, iss. 6, 2017.
    [Abstract]

    Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps ({NET}) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B ({NF}-{κB}), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

    @article{citeulike:14412929,
    abstract = {Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps ({NET}) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B ({NF}-{κB}), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.},
    author = {Gammoh, Nour Zahi Z. and Rink, Lothar},
    citeulike-article-id = {14412929},
    citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/28629136},
    citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=28629136},
    day = {17},
    issn = {2072-6643},
    journal = {Nutrients},
    month = jun,
    number = {6},
    pmid = {28629136},
    posted-at = {2017-08-11 17:56:32},
    priority = {2},
    title = {Zinc in Infection and Inflammation.},
    url = {http://view.ncbi.nlm.nih.gov/pubmed/28629136},
    volume = {9},
    year = {2017}
    }

  • H. Nguyen, F. Rineau, J. Vangronsveld, A. Cuypers, J. V. Colpaert, and J. Ruytinx, “A novel, highly conserved metallothionein family in basidiomycete fungi and characterization of two representative SlMTa and SlMTb genes in the ectomycorrhizal fungus suillus luteus,” Environmental microbiology, 2017. doi:10.1111/1462-2920.13729
    @article{citeulike:14362917,
    author = {Nguyen, Hoai and Rineau, Fran\c{c}ois and Vangronsveld, Jaco and Cuypers, Ann and Colpaert, Jan V. and Ruytinx, Joske},
    citeulike-article-id = {14362917},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/1462-2920.13729},
    doi = {10.1111/1462-2920.13729},
    issn = {14622912},
    journal = {Environmental Microbiology},
    month = apr,
    posted-at = {2017-05-25 14:35:59},
    priority = {2},
    title = {A novel, highly conserved metallothionein family in basidiomycete fungi and characterization of two representative
    {SlMTa}
    and
    {SlMTb}
    genes in the ectomycorrhizal fungus
    Suillus luteus},
    url = {http://dx.doi.org/10.1111/1462-2920.13729},
    year = {2017}
    }

  • T. Maxel, P. F. Svendsen, K. Smidt, J. K. Lauridsen, B. Brock, S. B. Pedersen, J. Rungby, and A. Larsen, “Expression patterns and correlations with metabolic markers of zinc transporters ZIP14 and ZNT1 in obesity and polycystic ovary syndrome,” Frontiers in endocrinology, vol. 8, 2017. doi:10.3389/fendo.2017.00038
    @article{citeulike:14362912,
    author = {Maxel, Trine and Svendsen, Pernille F. and Smidt, Kamille and Lauridsen, Jesper K. and Brock, Birgitte and Pedersen, Steen B. and Rungby, J{\o}rgen and Larsen, Agnete},
    citeulike-article-id = {14362912},
    citeulike-linkout-0 = {http://dx.doi.org/10.3389/fendo.2017.00038},
    day = {02},
    doi = {10.3389/fendo.2017.00038},
    issn = {1664-2392},
    journal = {Frontiers in Endocrinology},
    month = mar,
    posted-at = {2017-05-25 14:34:55},
    priority = {2},
    title = {Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters {ZIP14} and {ZNT1} in Obesity and Polycystic Ovary Syndrome},
    url = {http://dx.doi.org/10.3389/fendo.2017.00038},
    volume = {8},
    year = {2017}
    }

  • L. Lobo, M. Costas-Rodríguez, J. C. de Vicente, R. Pereiro, F. Vanhaecke, and A. Sanz-Medel, “Elemental and isotopic analysis of oral squamous cell carcinoma tissues using sector-field and multi-collector ICP-mass spectrometry,” Talanta, vol. 165, pp. 92-97, 2017. doi:10.1016/j.talanta.2016.12.007
    [Abstract]

    Elemental & isotopic composition in tissues of oral cancer patients are investigated. Tumor and non-tumor tissues were explored by sector field and multi-collector {ICP}-{MS}. Elemental analysis showed increased levels of Mg, K and P in the tumor tissues. Conversely to {δ66Zn}, {δ65Cu} provided a clear distinction tumor vs non tumor tissues. Elemental and isotopic analysis via single-collector and multi-collector {ICP}-mass spectrometry, respectively, have been explored as a tool for identifying potential differences between non-tumor and oral squamous cell carcinoma tissues. Elemental concentrations of major and minor elements, known to be essential for different processes in the cell (i.e. Na, Ca, Mg, K, P, Fe, Cu and Zn), have been determined and results for cancerous and non-cancerous tissues collected from the same individual have been compared. Among the elements studied, only Mg, K and P turned out to be significantly higher in concentration in the tumor tissues. However, a shift towards higher and wider concentration ranges has also been observed for Cu and Zn in the tumor samples, whereas for Ca lower concentrations were established. Possible isotope ratio variations for Cu and Zn in both biological tissues have also been evaluated with the same goal. {δ66Zn} results did not provide an obvious trend, but in the case of Cu, a clear distinction between the tumor and non-tumor tissues was observed: {δ65Cu} values ranged between −0.68\% and 0.03\% in the non-tumor tissues, whereas tumor samples turned out to be enriched in {65Cu}, with {δ65Cu} values between 0.10\% and 0.93\%. These results confirm the considerable potential of isotopic and elemental studies for biomedical purposes.

    @article{citeulike:14273873,
    abstract = { Elemental \& isotopic composition in tissues of oral cancer patients are investigated. Tumor and non-tumor tissues were explored by sector field and multi-collector {ICP}-{MS}. Elemental analysis showed increased levels of Mg, K and P in the tumor tissues. Conversely to {\^{I}´66Zn}, {\^{I}´65Cu} provided a clear distinction tumor vs non tumor tissues. Elemental and isotopic analysis via single-collector and multi-collector {ICP}-mass spectrometry, respectively, have been explored as a tool for identifying potential differences between non-tumor and oral squamous cell carcinoma tissues. Elemental concentrations of major and minor elements, known to be essential for different processes in the cell (i.e. Na, Ca, Mg, K, P, Fe, Cu and Zn), have been determined and results for cancerous and non-cancerous tissues collected from the same individual have been compared. Among the elements studied, only Mg, K and P turned out to be significantly higher in concentration in the tumor tissues. However, a shift towards higher and wider concentration ranges has also been observed for Cu and Zn in the tumor samples, whereas for Ca lower concentrations were established. Possible isotope ratio variations for Cu and Zn in both biological tissues have also been evaluated with the same goal. {\^{I}´66Zn} results did not provide an obvious trend, but in the case of Cu, a clear distinction between the tumor and non-tumor tissues was observed: {\^{I}´65Cu} values ranged between −0.68\% and 0.03\% in the non-tumor tissues, whereas tumor samples turned out to be enriched in {65Cu}, with {\^{I}´65Cu} values between 0.10\% and 0.93\%. These results confirm the considerable potential of isotopic and elemental studies for biomedical purposes. },
    author = {Lobo, Lara and Costas-Rodr\'{\i}guez, Marta and de Vicente, Juan C. and Pereiro, Rosario and Vanhaecke, Frank and Sanz-Medel, Alfredo},
    citeulike-article-id = {14273873},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.talanta.2016.12.007},
    doi = {10.1016/j.talanta.2016.12.007},
    issn = {00399140},
    journal = {Talanta},
    month = apr,
    pages = {92--97},
    posted-at = {2017-02-07 16:57:55},
    priority = {2},
    title = {Elemental and isotopic analysis of oral squamous cell carcinoma tissues using sector-field and multi-collector {ICP}-mass spectrometry},
    url = {http://dx.doi.org/10.1016/j.talanta.2016.12.007},
    volume = {165},
    year = {2017}
    }

  • Y. Li, L. Andereggen, K. Yuki, K. Omura, Y. Yin, H. Y. Gilbert, B. Erdogan, M. S. Asdourian, C. Shrock, S. de Lima, U. P. Apfel, Y. Zhuo, M. Hershfinkel, S. J. Lippard, P. A. Rosenberg, and L. Benowitz, “Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.,” Proceedings of the national academy of sciences of the united states of america, vol. 114, iss. 2, 2017.
    [Abstract]

    Retinal ganglion cells ({RGCs}), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas {RGC} death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to {RGCs} via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein {ZnT}-3, and deletion of slc30a3, the gene encoding {ZnT}-3, promotes {RGC} survival and axon regeneration. Intravitreal injection of Zn(2+) chelators enables many {RGCs} to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured {RGCs}, and point to Zn(2+) chelation as a strategy to promote long-term {RGC} protection and enhance axon regeneration.

    @article{citeulike:14273872,
    abstract = {Retinal ganglion cells ({RGCs}), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas {RGC} death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to {RGCs} via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein {ZnT}-3, and deletion of slc30a3, the gene encoding {ZnT}-3, promotes {RGC} survival and axon regeneration. Intravitreal injection of Zn(2+) chelators enables many {RGCs} to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured {RGCs}, and point to Zn(2+) chelation as a strategy to promote long-term {RGC} protection and enhance axon regeneration.},
    author = {Li, Yiqing and Andereggen, Lukas and Yuki, Kenya and Omura, Kumiko and Yin, Yuqin and Gilbert, Hui-Ya Y. and Erdogan, Burcu and Asdourian, Maria S. and Shrock, Christine and de Lima, Silmara and Apfel, Ulf-Peter P. and Zhuo, Yehong and Hershfinkel, Michal and Lippard, Stephen J. and Rosenberg, Paul A. and Benowitz, Larry},
    citeulike-article-id = {14273872},
    citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/28049831},
    citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=28049831},
    day = {10},
    issn = {1091-6490},
    journal = {Proceedings of the National Academy of Sciences of the United States of America},
    month = jan,
    number = {2},
    pmid = {28049831},
    posted-at = {2017-02-07 16:57:20},
    priority = {2},
    title = {Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.},
    url = {http://view.ncbi.nlm.nih.gov/pubmed/28049831},
    volume = {114},
    year = {2017}
    }

  • L. Sunuwar, H. Asraf, M. Donowitz, I. Sekler, and M. Hershfinkel, “The zn2+-sensing receptor, ZnR/GPR39, upregulates colonocytic cl− absorption, via basolateral KCC1, and reduces fluid loss,” Biochimica et biophysica acta (bba) – molecular basis of disease, vol. 1863, iss. 4, pp. 947-960, 2017. doi:10.1016/j.bbadis.2017.01.009
    [Abstract]

    Although diarrhea is a major cause of morbidity and lethality, effective targets for regulation of epithelial transport are not available. A Zn2+-sensing receptor, {ZnR}/{GPR39}, is expressed on colonocytes and is essential for Cl- absorption regulation via {K+/Cl}- cotransporter, {KCC1}. {KCC1} is basolaterally expressed in human and mouse colonocytes, providing a novel pathway for Cl- absorption. {ZnR}/{GPR39} and {KCC1} are essential for reducing fluid secretion induced by cholera toxin in vivo. {ZnR}/{GPR39} is an excellent target for of specific and effective anti-diarrheal drugs that can be independent of patients dietary zinc status. Administration of zinc, as a complement to oral rehydration solutions, effectively diminishes duration and severity of diarrhea, but it is not known whether it merely fulfills a nutritional deficiency, or if zinc has a direct role of regulating solute absorption. We show that Zn2+ acts via a specific receptor, {ZnR}/{GPR39}, to reduce fluid loss. Intestinal fluid secretion triggered by cholera toxin ({CTx}) was lower in {WT} mice compared to {ZnR}/{GPR39} {KO}. In the absence of dietary Zn2+ we observed similar fluid accumulation in {WT} and {ZnR}/{GPR39} {KO} mice, indicating that Zn2+ and {ZnR}/{GPR39} are both required for a beneficial effect of Zn2+ in diarrhea. In primary colonocytes and in Caco-2 colonocytic cells, activation of {ZnR}/{GPR39} enhanced Cl− transport, a critical factor in diarrhea, by upregulating {K+/Cl}− cotransporter ({KCC1}) activity. Importantly, we show basolateral expression of {KCC1} in mouse and human colonocytes, thus identifying a novel Cl− absorption pathway. Finally, inhibition of {KCC}-dependent Cl− transport enhanced {CTx}-induced fluid loss. Altogether, our data indicate that Zn2+ acting via {ZnR}/{GPR39} has a direct role in controlling Cl− absorption via upregulation of basolateral {KCC1} in the colon. Moreover, colonocytic {ZnR}/{GPR39} and {KCC1} reduce water loss during diarrhea and may therefore serve as effective drug targets.

    @article{citeulike:14273871,
    abstract = { Although diarrhea is a major cause of morbidity and lethality, effective targets for regulation of epithelial transport are not available. A Zn2+-sensing receptor, {ZnR}/{GPR39}, is expressed on colonocytes and is essential for Cl- absorption regulation via {K+/Cl}- cotransporter, {KCC1}. {KCC1} is basolaterally expressed in human and mouse colonocytes, providing a novel pathway for Cl- absorption. {ZnR}/{GPR39} and {KCC1} are essential for reducing fluid secretion induced by cholera toxin in vivo. {ZnR}/{GPR39} is an excellent target for of specific and effective anti-diarrheal drugs that can be independent of patients dietary zinc status. Administration of zinc, as a complement to oral rehydration solutions, effectively diminishes duration and severity of diarrhea, but it is not known whether it merely fulfills a nutritional deficiency, or if zinc has a direct role of regulating solute absorption. We show that Zn2+ acts via a specific receptor, {ZnR}/{GPR39}, to reduce fluid loss. Intestinal fluid secretion triggered by cholera toxin ({CTx}) was lower in {WT} mice compared to {ZnR}/{GPR39} {KO}. In the absence of dietary Zn2+ we observed similar fluid accumulation in {WT} and {ZnR}/{GPR39} {KO} mice, indicating that Zn2+ and {ZnR}/{GPR39} are both required for a beneficial effect of Zn2+ in diarrhea. In primary colonocytes and in Caco-2 colonocytic cells, activation of {ZnR}/{GPR39} enhanced Cl− transport, a critical factor in diarrhea, by upregulating {K+/Cl}− cotransporter ({KCC1}) activity. Importantly, we show basolateral expression of {KCC1} in mouse and human colonocytes, thus identifying a novel Cl− absorption pathway. Finally, inhibition of {KCC}-dependent Cl− transport enhanced {CTx}-induced fluid loss. Altogether, our data indicate that Zn2+ acting via {ZnR}/{GPR39} has a direct role in controlling Cl− absorption via upregulation of basolateral {KCC1} in the colon. Moreover, colonocytic {ZnR}/{GPR39} and {KCC1} reduce water loss during diarrhea and may therefore serve as effective drug targets.},
    author = {Sunuwar, Laxmi and Asraf, Hila and Donowitz, Mark and Sekler, Israel and Hershfinkel, Michal},
    citeulike-article-id = {14273871},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbadis.2017.01.009},
    doi = {10.1016/j.bbadis.2017.01.009},
    issn = {09254439},
    journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},
    month = apr,
    number = {4},
    pages = {947--960},
    posted-at = {2017-02-07 16:56:53},
    priority = {2},
    title = {The Zn2+-sensing receptor, {ZnR}/{GPR39}, upregulates colonocytic Cl− absorption, via basolateral {KCC1}, and reduces fluid loss},
    url = {http://dx.doi.org/10.1016/j.bbadis.2017.01.009},
    volume = {1863},
    year = {2017}
    }

2016

  • P. Adam, S. Křížková, Z. Heger, P. Babula, V. Pekařík, M. Vaculovičoá, C. M. Gomes, R. Kizek, and V. Adam, “Metallothioneins in prion- and Amyloid-Related diseases.,” Journal of alzheimer’s disease : jad, vol. 51, iss. 3, pp. 637-656, 2016.
    [Abstract]

    Prion and other amyloid-forming diseases represent a group of neurodegenerative disorders that affect both animals and humans. The role of metal ions, especially copper and zinc is studied intensively in connection with these diseases. Their involvement in protein misfolding and aggregation and their role in creation of reactive oxygen species have been shown. Recent data also show that metal ions not only bind the proteins with high affinity, but also modify their biochemical properties, making them important players in prion-related diseases. In particular, the level of zinc ions is tightly regulated by several mechanisms, including transporter proteins and the low molecular mass thiol-rich metallothioneins. From four metallothionein isoforms, metallothionein-3, a unique brain-specific metalloprotein, plays a crucial role only in this regulation. This review critically evaluates the involvement of metallothioneins in prion- and amyloid-related diseases in connection with the relationship between metallothionein isoforms and metal ion regulation of their homeostasis.

    @article{citeulike:14273864,
    abstract = {Prion and other amyloid-forming diseases represent a group of neurodegenerative disorders that affect both animals and humans. The role of metal ions, especially copper and zinc is studied intensively in connection with these diseases. Their involvement in protein misfolding and aggregation and their role in creation of reactive oxygen species have been shown. Recent data also show that metal ions not only bind the proteins with high affinity, but also modify their biochemical properties, making them important players in prion-related diseases. In particular, the level of zinc ions is tightly regulated by several mechanisms, including transporter proteins and the low molecular mass thiol-rich metallothioneins. From four metallothionein isoforms, metallothionein-3, a unique brain-specific metalloprotein, plays a crucial role only in this regulation. This review critically evaluates the involvement of metallothioneins in prion- and amyloid-related diseases in connection with the relationship between metallothionein isoforms and metal ion regulation of their homeostasis.},
    author = {Adam, Pavl\'{\i}na and K\v{r}\'{\i}\v{z}kov\'{a}, So\v{n}a and Heger, Zbyn\v{e}k and Babula, Petr and Peka\v{r}\'{\i}k, Vladim\'{\i}r and Vaculovi\v{c}o\'{a}, Mark\'{e}ta and Gomes, Cl\'{a}udio M. and Kizek, Ren\'{e} and Adam, Vojt\v{e}ch},
    citeulike-article-id = {14273864},
    citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/26923022},
    citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=26923022},
    issn = {1875-8908},
    journal = {Journal of Alzheimer's disease : JAD},
    number = {3},
    pages = {637--656},
    pmid = {26923022},
    posted-at = {2017-02-07 16:44:38},
    priority = {2},
    title = {Metallothioneins in Prion- and {Amyloid-Related} Diseases.},
    url = {http://view.ncbi.nlm.nih.gov/pubmed/26923022},
    volume = {51},
    year = {2016}
    }

  • A. M. Hessels, K. M. Taylor, and M. Merkx, “Monitoring cytosolic and ER zn2+ in stimulated breast cancer cells using genetically encoded FRET sensors,” Metallomics, vol. 8, iss. 2, pp. 211-217, 2016. doi:10.1039/C5MT00257E
    [Abstract]

    The Zn2+-specific ion channel {ZIP7} has been implicated to play an important role in releasing Zn2+ from the {ER}. External stimulation of breast cancer cells has been proposed to induce phosphorylation of {ZIP7} by {CK2}[small alpha], resulting in {ZIP7}-mediated Zn2+ release from the {ER} into the cytosol. Here, we examined whether changes in cytosolic and {ER} Zn2+ concentrations can be detected upon such external stimuli. Two previously developed {FRET} sensors for Zn2+, {eZinCh}-2 (Kd = 1 {nM} at {pH} 7.1) and {eCALWY}-4 (Kd = 0.63 {nM} at {pH} 7.1), were expressed in both the cytosol and the {ER} of wild-type {MCF}-7 and {TamR} cells. Treatment of {MCF}-7 and {TamR} cells with external Zn2+ and pyrithione, one of the previously used triggers, resulted in an immediate increase in free Zn2+ in both cytosol and {ER}, suggesting that Zn2+ was directly transferred across the cellular membranes by pyrithione. Cells treated with a second trigger, {EGF}/ionomycin, showed no changes in intracellular Zn2+ levels, neither in multicolor imaging experiments that allowed simultaneous imaging of cytosolic and {ER} Zn2+, nor in experiments in which cytosolic and {ER} Zn2+ were monitored separately. In contrast to previous work using small-molecule fluorescent dyes, these results indicate that {EGF}-ionomycin treatment does not result in significant changes in cytosolic Zn2+ levels as a result from Zn2+ release from the {ER}. These results underline the importance of using genetically encoded fluorescent sensors to complement and verify intracellular imaging experiments with synthetic fluorescent Zn2+ dyes.

    @article{citeulike:14273863,
    abstract = {The Zn2+-specific ion channel {ZIP7} has been implicated to play an important role in releasing Zn2+ from the {ER}. External stimulation of breast cancer cells has been proposed to induce phosphorylation of {ZIP7} by {CK2}[small alpha], resulting in {ZIP7}-mediated Zn2+ release from the {ER} into the cytosol. Here, we examined whether changes in cytosolic and {ER} Zn2+ concentrations can be detected upon such external stimuli. Two previously developed {FRET} sensors for Zn2+, {eZinCh}-2 (Kd = 1 {nM} at {pH} 7.1) and {eCALWY}-4 (Kd = 0.63 {nM} at {pH} 7.1), were expressed in both the cytosol and the {ER} of wild-type {MCF}-7 and {TamR} cells. Treatment of {MCF}-7 and {TamR} cells with external Zn2+ and pyrithione, one of the previously used triggers, resulted in an immediate increase in free Zn2+ in both cytosol and {ER}, suggesting that Zn2+ was directly transferred across the cellular membranes by pyrithione. Cells treated with a second trigger, {EGF}/ionomycin, showed no changes in intracellular Zn2+ levels, neither in multicolor imaging experiments that allowed simultaneous imaging of cytosolic and {ER} Zn2+, nor in experiments in which cytosolic and {ER} Zn2+ were monitored separately. In contrast to previous work using small-molecule fluorescent dyes, these results indicate that {EGF}-ionomycin treatment does not result in significant changes in cytosolic Zn2+ levels as a result from Zn2+ release from the {ER}. These results underline the importance of using genetically encoded fluorescent sensors to complement and verify intracellular imaging experiments with synthetic fluorescent Zn2+ dyes.},
    author = {Hessels, Anne M. and Taylor, Kathryn M. and Merkx, Maarten},
    citeulike-article-id = {14273863},
    citeulike-linkout-0 = {http://dx.doi.org/10.1039/C5MT00257E},
    doi = {10.1039/C5MT00257E},
    issn = {1756-5901},
    journal = {Metallomics},
    number = {2},
    pages = {211--217},
    posted-at = {2017-02-07 16:43:42},
    priority = {2},
    publisher = {The Royal Society of Chemistry},
    title = {Monitoring cytosolic and {ER} Zn2+ in stimulated breast cancer cells using genetically encoded {FRET} sensors},
    url = {http://dx.doi.org/10.1039/C5MT00257E},
    volume = {8},
    year = {2016}
    }

  • E. Rosenkranz, C. H. D. Metz, M. Maywald, R. Hilgers, I. Weßels, T. Senff, H. Haase, M. Jäger, M. Ott, R. Aspinall, B. Plümäkers, and L. Rink, “Zinc supplementation induces regulatory t cells by inhibition of sirt-1 deacetylase in mixed lymphocyte cultures,” Molecular nutrition & food research, vol. 60, iss. 3, pp. 661-671, 2016. doi:10.1002/mnfr.201500524
    @article{citeulike:14273861,
    author = {Rosenkranz, Eva and Metz, Claudia H. D. and Maywald, Martina and Hilgers, Ralf-Dieter and We{\ss}els, Inga and Senff, Tina and Haase, Hajo and J\"{a}ger, Maximilian and Ott, Melanie and Aspinall, Richard and Pl\"{u}m\"{a}kers, Birgit and Rink, Lothar},
    citeulike-article-id = {14273861},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/mnfr.201500524},
    doi = {10.1002/mnfr.201500524},
    issn = {1613-4133},
    journal = {Molecular Nutrition \& Food Research},
    keywords = {cells, foxp3, regulatory, sirt-1, t, tolerance, zinc},
    number = {3},
    pages = {661--671},
    posted-at = {2017-02-07 16:42:44},
    priority = {2},
    title = {Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures},
    url = {http://dx.doi.org/10.1002/mnfr.201500524},
    volume = {60},
    year = {2016}
    }

  • K. Smidt, A. Larsen, A. Br{o}nden, K. S. S{o}rensen, J. V. Nielsen, J. Praetorius, P. M. Martensen, and J. Rungby, “The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression,” Biometals, vol. 29, iss. 2, pp. 287-298, 2016. doi:10.1007/s10534-016-9915-7
    [Abstract]

    Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting ({ZNTs}) proteins. The role of different {ZNTs} in the beta cells is currently being clarified. {ZNT8} transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas {ZNT3} knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of {ZNT3} by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of {ZNT3} in a pancreatic beta cell line, {INS}-{1E} overexpressing {ZNT3}. In {INS}-{1E} cells, we found that {ZNT3} was abundant in insulin containing granules located close to the plasma membrane. The level of {ZNT8} {mRNA} was significantly decreased upon over-expression of {ZNT3} at different glucose concentrations (5, 11 and 21 {mM} glucose). {ZNT3} over-expression decreased insulin content and insulin secretion whereas {ZNT3} over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 {mM}). Our data suggest that {ZNT3} and {ZNT8} (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since {mRNA} expression of {ZNT3} was inversely correlated to {ZNT8} and {ZNT3} over-expression reduced insulin synthesis and secretion in {INS}-{1E} cells. {ZNT3} over-expression improved cell survival.

    @article{Smidt2016,
    abstract = {Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting ({ZNTs}) proteins. The role of different {ZNTs} in the beta cells is currently being clarified. {ZNT8} transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas {ZNT3} knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of {ZNT3} by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of {ZNT3} in a pancreatic beta cell line, {INS}-{1E} overexpressing {ZNT3}. In {INS}-{1E} cells, we found that {ZNT3} was abundant in insulin containing granules located close to the plasma membrane. The level of {ZNT8} {mRNA} was significantly decreased upon over-expression of {ZNT3} at different glucose concentrations (5, 11 and 21 {mM} glucose). {ZNT3} over-expression decreased insulin content and insulin secretion whereas {ZNT3} over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 {mM}). Our data suggest that {ZNT3} and {ZNT8} (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since {mRNA} expression of {ZNT3} was inversely correlated to {ZNT8} and {ZNT3} over-expression reduced insulin synthesis and secretion in {INS}-{1E} cells. {ZNT3} over-expression improved cell survival.},
    author = {Smidt, Kamille and Larsen, Agnete and Br{\o}nden, Andreas and S{\o}rensen, Karen S. and Nielsen, Julie V. and Praetorius, Jeppe and Martensen, Pia M. and Rungby, J{\o}rgen},
    citeulike-article-id = {14273857},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s10534-016-9915-7},
    doi = {10.1007/s10534-016-9915-7},
    issn = {1572-8773},
    journal = {BioMetals},
    number = {2},
    pages = {287--298},
    posted-at = {2017-02-07 16:32:33},
    priority = {2},
    title = {The zinc transporter {ZNT3} co-localizes with insulin in {INS}-{1E} pancreatic beta cells and influences cell survival, insulin secretion capacity, and {ZNT8} expression},
    url = {http://dx.doi.org/10.1007/s10534-016-9915-7},
    volume = {29},
    year = {2016}
    }

  • O. Januszko, D. Madej, A. Brzozowska, and J. Kaluza, “Iron absorption after introducing and discontinuation of iron and zinc supplementation in rats,” Journal of trace elements in medicine and biology, vol. 35, pp. 77-82, 2016. doi:10.1016/j.jtemb.2016.01.013
    [Abstract]

    Abstract The aim of this study was to investigate the changes in iron apparent absorption ({IAA}\%) during and after iron and zinc supplementation in rats. The study was conducted on 6-week old male Wistar rats in 3 stages: 4-week period of adaptation to the control (C) and iron deficient (D) diets (stage I); 4-week period of supplementation with 10-time more iron ({CSFe}, {DSFe}), zinc ({CSZn}, {DSZn}) or both iron and zinc ({CSFeZn}, {DSFeZn}) compared to C diet (stage {II}); 2-week of post-supplementation period (rats were fed the same diets as in the adaptation period, stage {III}). {IAA}\% was measured in five consecutive days directly after introducing and discontinuation of iron and zinc supplementation as well as in the end of stage {II} (days: 22–24th) and stage {III} (days: 8–10th). Overall in the second day after introducing and in the fifth day after discontinuation of iron or iron and zinc supplementation, the {IAA}\% had undergone to the level compatible with the values in the end of each stage. At the end of stage {II}, {IAA}\% in {CSFeZn} (54.1 ± 2.7\%) rats was not different from the {IAA}\% in {CSFe} rats (53.9 ± 1.9\%), but in {DSFeZn} group {IAA}\% (49.4 ± 2.1\%) was significantly lower than in {DSFe} (57.4 ± 2.3\%) group. Moreover, {IAA}\% after stage {II} and stage {III} in {DSZn} group was significantly lower (39.2 ± 2.8\% and 38.6 ± 2.6\%, respectively) than in group D (60.7 ± 1.9\% and 54.3 ± 3.0\%, respectively). In conclusion, zinc administered simultaneously with iron ({Zn:Fe} weight ratio = 1:1) decreased {IAA}\% in adult rats fed on iron deficient diet, but not in rats fed on control diet. {IAA}\% reduction by zinc supplementation has been extended to 10 days after discontinuation of the treatment. Adaptation of the rats to high doses of iron or iron and zinc and also to the cessation of these treatments was relatively fast. However, {IAA}\% was stabilized faster after introducing the supplementation than it’s discontinuation.

    @article{citeulike:14273856,
    abstract = {Abstract The aim of this study was to investigate the changes in iron apparent absorption ({IAA}\%) during and after iron and zinc supplementation in rats. The study was conducted on 6-week old male Wistar rats in 3 stages: 4-week period of adaptation to the control (C) and iron deficient (D) diets (stage I); 4-week period of supplementation with 10-time more iron ({CSFe}, {DSFe}), zinc ({CSZn}, {DSZn}) or both iron and zinc ({CSFeZn}, {DSFeZn}) compared to C diet (stage {II}); 2-week of post-supplementation period (rats were fed the same diets as in the adaptation period, stage {III}). {IAA}\% was measured in five consecutive days directly after introducing and discontinuation of iron and zinc supplementation as well as in the end of stage {II} (days: 22–24th) and stage {III} (days: 8–10th). Overall in the second day after introducing and in the fifth day after discontinuation of iron or iron and zinc supplementation, the {IAA}\% had undergone to the level compatible with the values in the end of each stage. At the end of stage {II}, {IAA}\% in {CSFeZn} (54.1 ± 2.7\%) rats was not different from the {IAA}\% in {CSFe} rats (53.9 ± 1.9\%), but in {DSFeZn} group {IAA}\% (49.4 ± 2.1\%) was significantly lower than in {DSFe} (57.4 ± 2.3\%) group. Moreover, {IAA}\% after stage {II} and stage {III} in {DSZn} group was significantly lower (39.2 ± 2.8\% and 38.6 ± 2.6\%, respectively) than in group D (60.7 ± 1.9\% and 54.3 ± 3.0\%, respectively). In conclusion, zinc administered simultaneously with iron ({Zn:Fe} weight ratio = 1:1) decreased {IAA}\% in adult rats fed on iron deficient diet, but not in rats fed on control diet. {IAA}\% reduction by zinc supplementation has been extended to 10 days after discontinuation of the treatment. Adaptation of the rats to high doses of iron or iron and zinc and also to the cessation of these treatments was relatively fast. However, {IAA}\% was stabilized faster after introducing the supplementation than it's discontinuation.},
    author = {Januszko, Olga and Madej, Dawid and Brzozowska, Anna and Kaluza, Joanna},
    citeulike-article-id = {14273856},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jtemb.2016.01.013},
    citeulike-linkout-1 = {\#},
    doi = {10.1016/j.jtemb.2016.01.013},
    issn = {0946-672X},
    journal = {Journal of Trace Elements in Medicine and Biology},
    keywords = {absorption, apparent, iron, post-supplementation, rats, supplementation, zinc},
    month = may,
    pages = {77--82},
    posted-at = {2017-02-07 16:27:50},
    priority = {2},
    title = {Iron absorption after introducing and discontinuation of iron and zinc supplementation in rats},
    url = {http://dx.doi.org/10.1016/j.jtemb.2016.01.013},
    volume = {35},
    year = {2016}
    }

  • R. Giacconi, L. Costarelli, F. Piacenza, A. Basso, L. Rink, E. Mariani, T. Fulop, G. Dedoussis, G. Herbein, M. Provinciali, J. Jajte, I. Lengyel, E. Mocchegiani, and M. Malavolta, “Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study.,” European journal of nutrition, 2016. doi:10.1007/s00394-016-1281-2
    [Abstract]

    Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal. We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis. Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, {RANTES} and Zn intake after adjustment for multiple confounders. {HSP70} +1267 {AA} genotype was an independent factor associated with Zn plasma concentrations. {Cu/Zn} ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels. Our findings show the most important independent determinants of plasma Zn concentration and {Cu/Zn} ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.

    @article{citeulike:14145884,
    abstract = {Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal. We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis. Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, {RANTES} and Zn intake after adjustment for multiple confounders. {HSP70} +1267 {AA} genotype was an independent factor associated with Zn plasma concentrations. {Cu/Zn} ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels. Our findings show the most important independent determinants of plasma Zn concentration and {Cu/Zn} ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.},
    author = {Giacconi, R. and Costarelli, L. and Piacenza, F. and Basso, A. and Rink, L. and Mariani, E. and Fulop, T. and Dedoussis, G. and Herbein, G. and Provinciali, M. and Jajte, J. and Lengyel, I. and Mocchegiani, E. and Malavolta, M.},
    citeulike-article-id = {14145884},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00394-016-1281-2},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27459881},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27459881},
    day = {26},
    doi = {10.1007/s00394-016-1281-2},
    issn = {1436-6215},
    journal = {European journal of nutrition},
    month = jul,
    pmid = {27459881},
    posted-at = {2016-09-24 18:15:46},
    priority = {2},
    title = {Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from {ZincAge} study.},
    url = {http://dx.doi.org/10.1007/s00394-016-1281-2},
    year = {2016}
    }

  • S. J. Aper, P. Dierickx, and M. Merkx, “Dual readout BRET/FRET sensors for measuring intracellular zinc.,” Acs chemical biology, 2016. doi:10.1021/acschembio.6b00453
    [Abstract]

    Genetically encoded {FRET}-based sensor proteins have significantly contributed to our current understanding of the intracellular functions of Zn(2+). However, the external excitation required for these fluorescent sensors can give rise to photobleaching and phototoxicity during long-term imaging, limits applications that suffer from autofluorescence and light scattering, and is not compatible with light-sensitive cells. For these applications, sensor proteins based on Bioluminescence Resonance Energy Transfer ({BRET}) would provide an attractive alternative. In this work, we used the bright and stable luciferase {NanoLuc} to create the first genetically encoded {BRET} sensors for measuring intracellular Zn(2+). Using a new sensor approach, the {NanoLuc} domain was fused to the Cerulean donor domain of two previously developed {FRET} sensors, {eCALWY} and {eZinCh}-2. In addition to preserving the excellent Zn(2+) affinity and specificity of their predecessors, these newly developed sensors enable both {BRET}- and {FRET}-based detection. While the dynamic range of the {BRET} signal for the {eCALWY}-based {BLCALWY}-1 sensor was limited by the presence of two competing {BRET} pathways, {BRET}/{FRET} sensors based on the {eZinCh}-2 scaffold ({BLZinCh}-1 and -2) yielded robust 25-30\% changes in {BRET} ratio. In addition, introduction of a chromophore-silencing mutation resulted in a {BRET}-only sensor ({BLZinCh}-3) with increased {BRET} response (50\%) and an unexpected 10-fold increase in Zn(2+) affinity. The combination of robust ratiometric response, physiologically relevant Zn(2+) affinities, and stable and bright luminescence signal offered by the {BLZinCh} sensors allowed monitoring of intracellular Zn(2+) in plate-based assays as well as intracellular {BRET}-based imaging in single living cells in real time.

    @article{citeulike:14145882,
    abstract = {Genetically encoded {FRET}-based sensor proteins have significantly contributed to our current understanding of the intracellular functions of Zn(2+). However, the external excitation required for these fluorescent sensors can give rise to photobleaching and phototoxicity during long-term imaging, limits applications that suffer from autofluorescence and light scattering, and is not compatible with light-sensitive cells. For these applications, sensor proteins based on Bioluminescence Resonance Energy Transfer ({BRET}) would provide an attractive alternative. In this work, we used the bright and stable luciferase {NanoLuc} to create the first genetically encoded {BRET} sensors for measuring intracellular Zn(2+). Using a new sensor approach, the {NanoLuc} domain was fused to the Cerulean donor domain of two previously developed {FRET} sensors, {eCALWY} and {eZinCh}-2. In addition to preserving the excellent Zn(2+) affinity and specificity of their predecessors, these newly developed sensors enable both {BRET}- and {FRET}-based detection. While the dynamic range of the {BRET} signal for the {eCALWY}-based {BLCALWY}-1 sensor was limited by the presence of two competing {BRET} pathways, {BRET}/{FRET} sensors based on the {eZinCh}-2 scaffold ({BLZinCh}-1 and -2) yielded robust 25-30\% changes in {BRET} ratio. In addition, introduction of a chromophore-silencing mutation resulted in a {BRET}-only sensor ({BLZinCh}-3) with increased {BRET} response (50\%) and an unexpected 10-fold increase in Zn(2+) affinity. The combination of robust ratiometric response, physiologically relevant Zn(2+) affinities, and stable and bright luminescence signal offered by the {BLZinCh} sensors allowed monitoring of intracellular Zn(2+) in plate-based assays as well as intracellular {BRET}-based imaging in single living cells in real time.},
    author = {Aper, Stijn J. and Dierickx, Pieterjan and Merkx, Maarten},
    citeulike-article-id = {14145882},
    citeulike-linkout-0 = {http://dx.doi.org/10.1021/acschembio.6b00453},
    citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/acschembio.6b00453},
    citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/27547982},
    citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=27547982},
    day = {1},
    doi = {10.1021/acschembio.6b00453},
    issn = {1554-8937},
    journal = {ACS chemical biology},
    month = sep,
    pmid = {27547982},
    posted-at = {2016-09-24 18:12:42},
    priority = {2},
    title = {Dual Readout {BRET}/{FRET} Sensors for Measuring Intracellular Zinc.},
    url = {http://dx.doi.org/10.1021/acschembio.6b00453},
    year = {2016}
    }

  • C. Abramovitch-Dahan, H. Asraf, M. Bogdanovic, I. Sekler, A. I. Bush, and M. Hershfinkel, “Amyloid β attenuates metabotropic zinc sensing receptor, mZnR/GPR39, dependent ca(2+) , ERK1/2 and clusterin signaling in neurons.,” Journal of neurochemistry, 2016. doi:10.1111/jnc.13760
    [Abstract]

    A hallmark of Alzheimer’s disease is accumulation of amyloid beta (Aβ) deposits, which are associated with neuronal dysfunction, spine loss, and impaired Ca(2+) homeostasis. Amyloid beta (Aβ) binds to and is aggregated by Zn(2+) , a metal released from synaptic glutamatergic vesicles during neuronal activity. Synaptically released Zn(2+) activates a metabotropic Gq-coupled Zn(2+) -sensing receptor, {mZnR}/{GPR39}, and induces Ca(2+) -signaling in post-synaptic neurons. We examined if Aβ, as a Zn(2+) binding protein, regulates neuronal Zn(2+) -signaling mediated by {mZnR}/{GPR39} using {SHSY}-{5Y} cells and cortical neurons from {GPR39} wild-type and knockout mice. Following acute or chronic treatment with Aβ neuronal Zn(2+) -dependent Ca(2+) release via {mZnR}/{GPR39} is significantly reduced. This impairment is overcome when excess Zn(2+) is applied, suggesting that impaired Ca(2+) -signaling results from Aβ binding of Zn(2+) . The Zn(2+) -dependent {mZnR}/{GPR39} activation triggers phosphorylation of extracellular regulated kinase and up-regulates expression of the chaperone protein clusterin (Clu). Importantly, neuronal Zn(2+) -dependent extracellular regulated kinase1/2 phosphorylation and up-regulation of Clu are attenuated by silencing {mZnR}/{GPR39} as well as by Aβ treatment. In contrast, Zn(2+) -dependent {AKT} phosphorylation is not mediated by {mZnR}/{GPR39} and is not attenuated by Aβ treatment. Thus, Zn(2+) signaling via {mZnR}/{GPR39} is distinctively disrupted by a critical pathological component of Alzheimer’s disease. Synaptically released Zn(2+) activates a Zn(2+) -sensing receptor, {mZnR}/{GPR39}, and induces Ca(2+) -signaling, followed by {ERK1}/2 {MAPK} activation and up-regulation of clusterin. Amyloid beta (Aβ) binds to Zn(2+) thus forming oligomers that are a hallmark of Alzheimer’s disease. We show that Aβ attenuates Zn(2+) -dependent Ca(2+) -responses, abolishes {ERK1}/2 activation and down-regulates clusterin expression. Thus, Zn(2+) signaling via {mZnR}/{GPR39} is disrupted by Aβ, a critical pathological component of Alzheimer’s disease. {\copyright} 2016 International Society for Neurochemistry.

    @article{citeulike:14145881,
    abstract = {A hallmark of Alzheimer's disease is accumulation of amyloid beta (Aβ) deposits, which are associated with neuronal dysfunction, spine loss, and impaired Ca(2+) homeostasis. Amyloid beta (Aβ) binds to and is aggregated by Zn(2+) , a metal released from synaptic glutamatergic vesicles during neuronal activity. Synaptically released Zn(2+) activates a metabotropic Gq-coupled Zn(2+) -sensing receptor, {mZnR}/{GPR39}, and induces Ca(2+) -signaling in post-synaptic neurons. We examined if Aβ, as a Zn(2+) binding protein, regulates neuronal Zn(2+) -signaling mediated by {mZnR}/{GPR39} using {SHSY}-{5Y} cells and cortical neurons from {GPR39} wild-type and knockout mice. Following acute or chronic treatment with Aβ neuronal Zn(2+) -dependent Ca(2+) release via {mZnR}/{GPR39} is significantly reduced. This impairment is overcome when excess Zn(2+) is applied, suggesting that impaired Ca(2+) -signaling results from Aβ binding of Zn(2+) . The Zn(2+) -dependent {mZnR}/{GPR39} activation triggers phosphorylation of extracellular regulated kinase and up-regulates expression of the chaperone protein clusterin (Clu). Importantly, neuronal Zn(2+) -dependent extracellular regulated kinase1/2 phosphorylation and up-regulation of Clu are attenuated by silencing {mZnR}/{GPR39} as well as by Aβ treatment. In contrast, Zn(2+) -dependent {AKT} phosphorylation is not mediated by {mZnR}/{GPR39} and is not attenuated by Aβ treatment. Thus, Zn(2+) signaling via {mZnR}/{GPR39} is distinctively disrupted by a critical pathological component of Alzheimer's disease. Synaptically released Zn(2+) activates a Zn(2+) -sensing receptor, {mZnR}/{GPR39}, and induces Ca(2+) -signaling, followed by {ERK1}/2 {MAPK} activation and up-regulation of clusterin. Amyloid beta (Aβ) binds to Zn(2+) thus forming oligomers that are a hallmark of Alzheimer's disease. We show that Aβ attenuates Zn(2+) -dependent Ca(2+) -responses, abolishes {ERK1}/2 activation and down-regulates clusterin expression. Thus, Zn(2+) signaling via {mZnR}/{GPR39} is disrupted by Aβ, a critical pathological component of Alzheimer's disease. {\copyright} 2016 International Society for Neurochemistry.},
    author = {Abramovitch-Dahan, Chen and Asraf, Hila and Bogdanovic, Milos and Sekler, Israel and Bush, Ashley I. and Hershfinkel, Michal},
    citeulike-article-id = {14145881},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/jnc.13760},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27501363},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27501363},
    day = {8},
    doi = {10.1111/jnc.13760},
    issn = {1471-4159},
    journal = {Journal of neurochemistry},
    month = aug,
    pmid = {27501363},
    posted-at = {2016-09-24 18:11:02},
    priority = {2},
    title = {Amyloid β attenuates metabotropic zinc sensing receptor, {mZnR}/{GPR39}, dependent Ca(2+) , {ERK1}/2 and Clusterin signaling in neurons.},
    url = {http://dx.doi.org/10.1111/jnc.13760},
    year = {2016}
    }

  • N. R. Johnston, R. K. Mitchell, E. Haythorne, M. P. P. Pessoa, F. Semplici, J. Ferrer, L. Piemonti, P. Marchetti, M. Bugliani, D. Bosco, E. Berishvili, P. Duncanson, M. Watkinson, J. Broichhagen, D. Trauner, G. A. Rutter, and D. J. Hodson, “Beta cell hubs dictate pancreatic islet responses to glucose.,” Cell metabolism, vol. 24, iss. 3, pp. 389-401, 2016. doi:10.1016/j.cmet.2016.06.020
    [Abstract]

    The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns. Hubs were metabolically adapted and targeted by both pro-inflammatory and glucolipotoxic insults to induce widespread β cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus. Copyright {\copyright} 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

    @article{citeulike:14145880,
    abstract = {The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns. Hubs were metabolically adapted and targeted by both pro-inflammatory and glucolipotoxic insults to induce widespread β cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus. Copyright {\copyright} 2016 The Author(s). Published by Elsevier Inc. All rights reserved.},
    author = {Johnston, Natalie R. and Mitchell, Ryan K. and Haythorne, Elizabeth and Pessoa, Maria Paiva P. and Semplici, Francesca and Ferrer, Jorge and Piemonti, Lorenzo and Marchetti, Piero and Bugliani, Marco and Bosco, Domenico and Berishvili, Ekaterine and Duncanson, Philip and Watkinson, Michael and Broichhagen, Johannes and Trauner, Dirk and Rutter, Guy A. and Hodson, David J.},
    citeulike-article-id = {14145880},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cmet.2016.06.020},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27452146},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27452146},
    day = {13},
    doi = {10.1016/j.cmet.2016.06.020},
    issn = {1932-7420},
    journal = {Cell metabolism},
    month = sep,
    number = {3},
    pages = {389--401},
    pmid = {27452146},
    posted-at = {2016-09-24 18:10:31},
    priority = {2},
    title = {Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose.},
    url = {http://dx.doi.org/10.1016/j.cmet.2016.06.020},
    volume = {24},
    year = {2016}
    }

  • V. Ključarić, R. Kobetić, J. Rinkovec, S. Kazazić, D. Gembarovski, D. Saftić, J. Matić, Ž. Ban, and B. Žinić, “ESI-MS studies of the non-covalent interactions between biologically important metal ions and n-sulfonylcytosine derivatives.,” Journal of mass spectrometry : jms, 2016. doi:10.1002/jms.3810
    [Abstract]

    The aim of this report is to present the electrospray ionization ({ESI}-{MS}) results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, {1-TsC}, 1 and N-1-methanesulfonylcytosine, {1-MsC}, 2 and their {Cu(II}) complexes {Cu(1-TsC}-N3)2 Cl2, 3 and {Cu(1-MsC}-N3)2 Cl2, 4 with biologically important cations: Na(+) , K(+) , Ca(2+) , Mg(2+) and Zn(2+) . The formation of various complex metal ions was observed. The alkali metals Na(+) and K(+) formed clusters due to electrostatic interactions. Ca(2+) and Mg(2+) salts produced the tris ligand and mixed ligand complexes. The interaction of Zn(2+) with 1-4 produced monometal and dimetal Zn(2+) complexes as a result of the affinity of Zn(2+) ions towards both O and N atoms. This article is protected by copyright. All rights reserved.

    @article{citeulike:14145879,
    abstract = {The aim of this report is to present the electrospray ionization ({ESI}-{MS}) results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, {1-TsC}, 1 and N-1-methanesulfonylcytosine, {1-MsC}, 2 and their {Cu(II}) complexes {Cu(1-TsC}-N3)2 Cl2, 3 and {Cu(1-MsC}-N3)2 Cl2, 4 with biologically important cations: Na(+) , K(+) , Ca(2+) , Mg(2+) and Zn(2+) . The formation of various complex metal ions was observed. The alkali metals Na(+) and K(+) formed clusters due to electrostatic interactions. Ca(2+) and Mg(2+) salts produced the tris ligand and mixed ligand complexes. The interaction of Zn(2+) with 1-4 produced monometal and dimetal Zn(2+) complexes as a result of the affinity of Zn(2+) ions towards both O and N atoms. This article is protected by copyright. All rights reserved.},
    author = {Klju\v{c}ari\'{c}, Valentina and Kobeti\'{c}, Renata and Rinkovec, Jasmina and Kazazi\'{c}, Snje\v{z}ana and Gembarovski, Dubravka and Safti\'{c}, Dijana and Mati\'{c}, Josipa and Ban, \v{Z}eljka and \v{Z}ini\'{c}, Biserka},
    citeulike-article-id = {14145879},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/jms.3810},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27405069},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27405069},
    day = {12},
    doi = {10.1002/jms.3810},
    issn = {1096-9888},
    journal = {Journal of mass spectrometry : JMS},
    month = jul,
    pmid = {27405069},
    posted-at = {2016-09-24 18:09:36},
    priority = {2},
    title = {{ESI}-{MS} studies of the non-covalent interactions between biologically important metal ions and N-sulfonylcytosine derivatives.},
    url = {http://dx.doi.org/10.1002/jms.3810},
    year = {2016}
    }

  • P. A. Gerber and G. A. Rutter, “The role of oxidative stress and hypoxia in pancreatic Beta-Cell dysfunction in diabetes mellitus.,” Antioxidants & redox signaling, 2016. doi:10.1089/ars.2016.6755
    [Abstract]

    Metabolic syndrome is a frequent precursor of type 2 diabetes mellitus ({T2D}), a disease that currently affects ∼8\% of the adult population worldwide. Pancreatic beta-cell dysfunction and loss are central to the disease process, although understanding of the underlying molecular mechanisms is still fragmentary. Oversupply of nutrients, including glucose and fatty acids, and the subsequent overstimulation of beta cells, are believed to be an important contributor to insulin secretory failure in {T2D}. Hypoxia has also recently been implicated in beta-cell damage. Accumulating evidence points to a role for oxidative stress in both processes. Although the production of reactive oxygen species ({ROS}) results from enhanced mitochondrial respiration during stimulation with glucose and other fuels, the expression of antioxidant defense genes is unusually low (or disallowed) in beta cells. Not all subjects with metabolic syndrome and hyperglycemia go on to develop full-blown diabetes, implying an important role in disease risk for gene-environment interactions. Possession of common risk alleles at the {SLC30A8} locus, encoding the beta-cell granule zinc transporter {ZnT8}, may affect cytosolic Zn(2+) concentrations and thus susceptibility to hypoxia and oxidative stress. Loss of normal beta-cell function, rather than total mass, is increasingly considered to be the major driver for impaired insulin secretion in diabetes. Better understanding of the role of oxidative changes, its modulation by genes involved in disease risk, and effects on beta-cell identity may facilitate the development of new therapeutic strategies to this disease. Antioxid. Redox Signal. 00, 000-000.

    @article{citeulike:14145877,
    abstract = {Metabolic syndrome is a frequent precursor of type 2 diabetes mellitus ({T2D}), a disease that currently affects ∼8\% of the adult population worldwide. Pancreatic beta-cell dysfunction and loss are central to the disease process, although understanding of the underlying molecular mechanisms is still fragmentary. Oversupply of nutrients, including glucose and fatty acids, and the subsequent overstimulation of beta cells, are believed to be an important contributor to insulin secretory failure in {T2D}. Hypoxia has also recently been implicated in beta-cell damage. Accumulating evidence points to a role for oxidative stress in both processes. Although the production of reactive oxygen species ({ROS}) results from enhanced mitochondrial respiration during stimulation with glucose and other fuels, the expression of antioxidant defense genes is unusually low (or disallowed) in beta cells. Not all subjects with metabolic syndrome and hyperglycemia go on to develop full-blown diabetes, implying an important role in disease risk for gene-environment interactions. Possession of common risk alleles at the {SLC30A8} locus, encoding the beta-cell granule zinc transporter {ZnT8}, may affect cytosolic Zn(2+) concentrations and thus susceptibility to hypoxia and oxidative stress. Loss of normal beta-cell function, rather than total mass, is increasingly considered to be the major driver for impaired insulin secretion in diabetes. Better understanding of the role of oxidative changes, its modulation by genes involved in disease risk, and effects on beta-cell identity may facilitate the development of new therapeutic strategies to this disease. Antioxid. Redox Signal. 00, 000-000.},
    author = {Gerber, Philipp A. and Rutter, Guy A.},
    citeulike-article-id = {14145877},
    citeulike-linkout-0 = {http://dx.doi.org/10.1089/ars.2016.6755},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27225690},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27225690},
    day = {30},
    doi = {10.1089/ars.2016.6755},
    issn = {1557-7716},
    journal = {Antioxidants \& redox signaling},
    month = jun,
    pmid = {27225690},
    posted-at = {2016-09-24 18:08:23},
    priority = {2},
    title = {The Role of Oxidative Stress and Hypoxia in Pancreatic {Beta-Cell} Dysfunction in Diabetes Mellitus.},
    url = {http://dx.doi.org/10.1089/ars.2016.6755},
    year = {2016}
    }

  • A. M. Hessels, K. M. Taylor, and M. Merkx, “Monitoring cytosolic and ER zn(2+) in stimulated breast cancer cells using genetically encoded FRET sensors.,” Metallomics : integrated biometal science, vol. 8, iss. 2, pp. 211-217, 2016. doi:10.1039/c5mt00257e
    [Abstract]

    The Zn(2+)-specific ion channel {ZIP7} has been implicated to play an important role in releasing Zn(2+) from the {ER}. External stimulation of breast cancer cells has been proposed to induce phosphorylation of {ZIP7} by {CK2α}, resulting in {ZIP7}-mediated Zn(2+) release from the {ER} into the cytosol. Here, we examined whether changes in cytosolic and {ER} Zn(2+) concentrations can be detected upon such external stimuli. Two previously developed {FRET} sensors for Zn(2+), {eZinCh}-2 (Kd = 1 {nM} at {pH} 7.1) and {eCALWY}-4 (Kd = 0.63 {nM} at {pH} 7.1), were expressed in both the cytosol and the {ER} of wild-type {MCF}-7 and {TamR} cells. Treatment of {MCF}-7 and {TamR} cells with external Zn(2+) and pyrithione, one of the previously used triggers, resulted in an immediate increase in free Zn(2+) in both cytosol and {ER}, suggesting that Zn(2+) was directly transferred across the cellular membranes by pyrithione. Cells treated with a second trigger, {EGF}/ionomycin, showed no changes in intracellular Zn(2+) levels, neither in multicolor imaging experiments that allowed simultaneous imaging of cytosolic and {ER} Zn(2+), nor in experiments in which cytosolic and {ER} Zn(2+) were monitored separately. In contrast to previous work using small-molecule fluorescent dyes, these results indicate that {EGF}-ionomycin treatment does not result in significant changes in cytosolic Zn(2+) levels as a result from Zn(2+) release from the {ER}. These results underline the importance of using genetically encoded fluorescent sensors to complement and verify intracellular imaging experiments with synthetic fluorescent Zn(2+) dyes.

    @article{citeulike:14145862,
    abstract = {The Zn(2+)-specific ion channel {ZIP7} has been implicated to play an important role in releasing Zn(2+) from the {ER}. External stimulation of breast cancer cells has been proposed to induce phosphorylation of {ZIP7} by {CK2α}, resulting in {ZIP7}-mediated Zn(2+) release from the {ER} into the cytosol. Here, we examined whether changes in cytosolic and {ER} Zn(2+) concentrations can be detected upon such external stimuli. Two previously developed {FRET} sensors for Zn(2+), {eZinCh}-2 (Kd = 1 {nM} at {pH} 7.1) and {eCALWY}-4 (Kd = 0.63 {nM} at {pH} 7.1), were expressed in both the cytosol and the {ER} of wild-type {MCF}-7 and {TamR} cells. Treatment of {MCF}-7 and {TamR} cells with external Zn(2+) and pyrithione, one of the previously used triggers, resulted in an immediate increase in free Zn(2+) in both cytosol and {ER}, suggesting that Zn(2+) was directly transferred across the cellular membranes by pyrithione. Cells treated with a second trigger, {EGF}/ionomycin, showed no changes in intracellular Zn(2+) levels, neither in multicolor imaging experiments that allowed simultaneous imaging of cytosolic and {ER} Zn(2+), nor in experiments in which cytosolic and {ER} Zn(2+) were monitored separately. In contrast to previous work using small-molecule fluorescent dyes, these results indicate that {EGF}-ionomycin treatment does not result in significant changes in cytosolic Zn(2+) levels as a result from Zn(2+) release from the {ER}. These results underline the importance of using genetically encoded fluorescent sensors to complement and verify intracellular imaging experiments with synthetic fluorescent Zn(2+) dyes.},
    author = {Hessels, Anne M. and Taylor, Kathryn M. and Merkx, Maarten},
    citeulike-article-id = {14145862},
    citeulike-linkout-0 = {http://dx.doi.org/10.1039/c5mt00257e},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26739447},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26739447},
    doi = {10.1039/c5mt00257e},
    issn = {1756-591X},
    journal = {Metallomics : integrated biometal science},
    month = feb,
    number = {2},
    pages = {211--217},
    pmid = {26739447},
    posted-at = {2016-09-24 17:44:20},
    priority = {2},
    title = {Monitoring cytosolic and {ER} Zn(2+) in stimulated breast cancer cells using genetically encoded {FRET} sensors.},
    url = {http://dx.doi.org/10.1039/c5mt00257e},
    volume = {8},
    year = {2016}
    }

  • S. J. Aper and M. Merkx, “Rewiring multidomain protein switches: transforming a fluorescent zn(2+) sensor into a Light-Responsive zn(2+) binding protein.,” Acs synthetic biology, vol. 5, iss. 7, pp. 698-709, 2016. doi:10.1021/acssynbio.6b00027
    [Abstract]

    Protein-based sensors and switches provide attractive tools for the real-time monitoring and control of molecular processes in complex biological environments. Fluorescent sensor proteins have been developed for a wide variety of small molecules, but the construction of genetically encoded light-responsive ligand binding proteins remains mostly unexplored. Here we present a generic approach to reengineer a previously developed {FRET}-based Zn(2+) sensor into a light-activatable Zn(2+) binding protein using a design strategy based on mutually exclusive domain interactions. These so-called {VividZn} proteins consist of two light-responsive Vivid domains that homodimerize upon illumination with blue light, thus preventing the binding of Zn(2+) between two Zn(2+) binding domains, Atox1 and {WD4}. Following optimization of the linker between {WD4} and the N-terminus of one of the Vivid domains, {VividZn} variants were obtained that show a 9- to 55-fold decrease in Zn(2+) affinity upon illumination, which is fully reversible following dark adaptation. The Zn(2+) affinities of the switch could be rationally tuned between 1 {pM} and 2 {nM} by systematic variation of linker length and mutation of one of the Zn(2+) binding residues. Similarly, introduction of mutations in the Vivid domains allowed tuning of the switching kinetics between 10 min and 7 h. Low expression levels in mammalian cells precluded the demonstration of light-induced perturbation of cytosolic Zn(2+) levels. Nonetheless, our results firmly establish the use of intramolecular Vivid dimerization as an attractive light-sensitive input module to rationally engineer light-responsive protein switches based on mutually exclusive domain interactions.

    @article{citeulike:14145861,
    abstract = {Protein-based sensors and switches provide attractive tools for the real-time monitoring and control of molecular processes in complex biological environments. Fluorescent sensor proteins have been developed for a wide variety of small molecules, but the construction of genetically encoded light-responsive ligand binding proteins remains mostly unexplored. Here we present a generic approach to reengineer a previously developed {FRET}-based Zn(2+) sensor into a light-activatable Zn(2+) binding protein using a design strategy based on mutually exclusive domain interactions. These so-called {VividZn} proteins consist of two light-responsive Vivid domains that homodimerize upon illumination with blue light, thus preventing the binding of Zn(2+) between two Zn(2+) binding domains, Atox1 and {WD4}. Following optimization of the linker between {WD4} and the N-terminus of one of the Vivid domains, {VividZn} variants were obtained that show a 9- to 55-fold decrease in Zn(2+) affinity upon illumination, which is fully reversible following dark adaptation. The Zn(2+) affinities of the switch could be rationally tuned between 1 {pM} and 2 {nM} by systematic variation of linker length and mutation of one of the Zn(2+) binding residues. Similarly, introduction of mutations in the Vivid domains allowed tuning of the switching kinetics between 10 min and 7 h. Low expression levels in mammalian cells precluded the demonstration of light-induced perturbation of cytosolic Zn(2+) levels. Nonetheless, our results firmly establish the use of intramolecular Vivid dimerization as an attractive light-sensitive input module to rationally engineer light-responsive protein switches based on mutually exclusive domain interactions.},
    author = {Aper, Stijn J. and Merkx, Maarten},
    citeulike-article-id = {14145861},
    citeulike-linkout-0 = {http://dx.doi.org/10.1021/acssynbio.6b00027},
    citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/acssynbio.6b00027},
    citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/27031076},
    citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=27031076},
    day = {15},
    doi = {10.1021/acssynbio.6b00027},
    issn = {2161-5063},
    journal = {ACS synthetic biology},
    month = jul,
    number = {7},
    pages = {698--709},
    pmid = {27031076},
    posted-at = {2016-09-24 17:43:22},
    priority = {2},
    title = {Rewiring Multidomain Protein Switches: Transforming a Fluorescent Zn(2+) Sensor into a {Light-Responsive} Zn(2+) Binding Protein.},
    url = {http://dx.doi.org/10.1021/acssynbio.6b00027},
    volume = {5},
    year = {2016}
    }

  • O. Januszko, D. Madej, A. Brzozowska, and J. Kaluza, “Iron absorption after introducing and discontinuation of iron and zinc supplementation in rats.,” Journal of trace elements in medicine and biology : organ of the society for minerals and trace elements (gms), vol. 35, pp. 77-82, 2016. doi:10.1016/j.jtemb.2016.01.013
    [Abstract]

    The aim of this study was to investigate the changes in iron apparent absorption ({IAA}\%) during and after iron and zinc supplementation in rats. The study was conducted on 6-week old male Wistar rats in 3 stages: 4-week period of adaptation to the control (C) and iron deficient (D) diets (stage I); 4-week period of supplementation with 10-time more iron ({CSFe}, {DSFe}), zinc ({CSZn}, {DSZn}) or both iron and zinc ({CSFeZn}, {DSFeZn}) compared to C diet (stage {II}); 2-week of post-supplementation period (rats were fed the same diets as in the adaptation period, stage {III}). {IAA}\% was measured in five consecutive days directly after introducing and discontinuation of iron and zinc supplementation as well as in the end of stage {II} (days: 22-24th) and stage {III} (days: 8-10th). Overall in the second day after introducing and in the fifth day after discontinuation of iron or iron and zinc supplementation, the {IAA}\% had undergone to the level compatible with the values in the end of each stage. At the end of stage {II}, {IAA}\% in {CSFeZn} (54.1 ± 2.7\%) rats was not different from the {IAA}\% in {CSFe} rats (53.9 ± 1.9\%), but in {DSFeZn} group {IAA}\% (49.4 ± 2.1\%) was significantly lower than in {DSFe} (57.4 ± 2.3\%) group. Moreover, {IAA}\% after stage {II} and stage {III} in {DSZn} group was significantly lower (39.2 ± 2.8\% and 38.6 ± 2.6\%, respectively) than in group D (60.7 ± 1.9\% and 54.3 ± 3.0\%, respectively). In conclusion, zinc administered simultaneously with iron ({Zn:Fe} weight ratio=1:1) decreased {IAA}\% in adult rats fed on iron deficient diet, but not in rats fed on control diet. {IAA}\% reduction by zinc supplementation has been extended to 10 days after discontinuation of the treatment. Adaptation of the rats to high doses of iron or iron and zinc and also to the cessation of these treatments was relatively fast. However, {IAA}\% was stabilized faster after introducing the supplementation than it’s discontinuation. Copyright {\copyright} 2016 Elsevier {GmbH}. All rights reserved.

    @article{citeulike:14145859,
    abstract = {The aim of this study was to investigate the changes in iron apparent absorption ({IAA}\%) during and after iron and zinc supplementation in rats. The study was conducted on 6-week old male Wistar rats in 3 stages: 4-week period of adaptation to the control (C) and iron deficient (D) diets (stage I); 4-week period of supplementation with 10-time more iron ({CSFe}, {DSFe}), zinc ({CSZn}, {DSZn}) or both iron and zinc ({CSFeZn}, {DSFeZn}) compared to C diet (stage {II}); 2-week of post-supplementation period (rats were fed the same diets as in the adaptation period, stage {III}). {IAA}\% was measured in five consecutive days directly after introducing and discontinuation of iron and zinc supplementation as well as in the end of stage {II} (days: 22-24th) and stage {III} (days: 8-10th). Overall in the second day after introducing and in the fifth day after discontinuation of iron or iron and zinc supplementation, the {IAA}\% had undergone to the level compatible with the values in the end of each stage. At the end of stage {II}, {IAA}\% in {CSFeZn} (54.1 ± 2.7\%) rats was not different from the {IAA}\% in {CSFe} rats (53.9 ± 1.9\%), but in {DSFeZn} group {IAA}\% (49.4 ± 2.1\%) was significantly lower than in {DSFe} (57.4 ± 2.3\%) group. Moreover, {IAA}\% after stage {II} and stage {III} in {DSZn} group was significantly lower (39.2 ± 2.8\% and 38.6 ± 2.6\%, respectively) than in group D (60.7 ± 1.9\% and 54.3 ± 3.0\%, respectively). In conclusion, zinc administered simultaneously with iron ({Zn:Fe} weight ratio=1:1) decreased {IAA}\% in adult rats fed on iron deficient diet, but not in rats fed on control diet. {IAA}\% reduction by zinc supplementation has been extended to 10 days after discontinuation of the treatment. Adaptation of the rats to high doses of iron or iron and zinc and also to the cessation of these treatments was relatively fast. However, {IAA}\% was stabilized faster after introducing the supplementation than it's discontinuation. Copyright {\copyright} 2016 Elsevier {GmbH}. All rights reserved.},
    author = {Januszko, Olga and Madej, Dawid and Brzozowska, Anna and Kaluza, Joanna},
    citeulike-article-id = {14145859},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jtemb.2016.01.013},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27049129},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27049129},
    doi = {10.1016/j.jtemb.2016.01.013},
    issn = {1878-3252},
    journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
    month = may,
    pages = {77--82},
    pmid = {27049129},
    posted-at = {2016-09-24 17:43:03},
    priority = {2},
    title = {Iron absorption after introducing and discontinuation of iron and zinc supplementation in rats.},
    url = {http://dx.doi.org/10.1016/j.jtemb.2016.01.013},
    volume = {35},
    year = {2016}
    }

  • W. M. Rangel, S. Thijs, J. Janssen, S. M. Oliveira Longatti, D. S. Bonaldi, P. R. Ribeiro, I. Jambon, N. Eevers, N. Weyens, J. Vangronsveld, and F. M. Moreira, “Native rhizobia from zn-mining soil promotes the growth of leucaena leucocephala on contaminated soil.,” International journal of phytoremediation, 2016. doi:10.1080/15226514.2016.1207600
    [Abstract]

    Plants on contaminated mining soils often show a reduced growth due to nutrient depletion as well as trace elements ({TE}) toxicity. Since those conditions threat plant’s survival, plant growth promoting rhizobacteria ({PGPR}) such as rhizobia, might be of crucial importance for plant colonization on {TE} contaminated soils. Native rhizobia from mining soils are promising candidates for bioaugmented phytoremediation of those soils as they are adapted to the specific conditions. In this work, rhizobia from Zn- and Cd-contaminated mining soils were in vitro screened for their plant growth promoting features (organic acids, indole-3-acetic-acid and siderophore production, 1-aminocyclopropane-1-carboxylate deaminase activity, and {Ca3(PO4})2 solubilization) and Zn- and Cd-resistance. In addition, some type and reference rhizobia strains were included in the study as well. The in vitro screening indicated that rhizobia and other native genera have great potential for phytoremediation purposes, by exerting, besides biological N2 fixation, other plant growth promoting traits. Leucaena {leucocephala-Mesorhizobium} sp. ({UFLA} 01-765) showed multi-element tolerance and an efficient symbiosis on contaminated soil deacresing the activities of antioxidative enzymes in shoots. This symbiosis is a promising combination to be used for phytostabilization concern.

    @article{citeulike:14145857,
    abstract = {Plants on contaminated mining soils often show a reduced growth due to nutrient depletion as well as trace elements ({TE}) toxicity. Since those conditions threat plant's survival, plant growth promoting rhizobacteria ({PGPR}) such as rhizobia, might be of crucial importance for plant colonization on {TE} contaminated soils. Native rhizobia from mining soils are promising candidates for bioaugmented phytoremediation of those soils as they are adapted to the specific conditions. In this work, rhizobia from Zn- and Cd-contaminated mining soils were in vitro screened for their plant growth promoting features (organic acids, indole-3-acetic-acid and siderophore production, 1-aminocyclopropane-1-carboxylate deaminase activity, and {Ca3(PO4})2 solubilization) and Zn- and Cd-resistance. In addition, some type and reference rhizobia strains were included in the study as well. The in vitro screening indicated that rhizobia and other native genera have great potential for phytoremediation purposes, by exerting, besides biological N2 fixation, other plant growth promoting traits. Leucaena {leucocephala-Mesorhizobium} sp. ({UFLA} 01-765) showed multi-element tolerance and an efficient symbiosis on contaminated soil deacresing the activities of antioxidative enzymes in shoots. This symbiosis is a promising combination to be used for phytostabilization concern.},
    author = {Rangel, Wesley M. and Thijs, Sofie and Janssen, Jolien and Oliveira Longatti, Silvia M. and Bonaldi, Daiane S. and Ribeiro, Paula R. and Jambon, Inge and Eevers, Nele and Weyens, Nele and Vangronsveld, Jaco and Moreira, Fatima M.},
    citeulike-article-id = {14145857},
    citeulike-linkout-0 = {http://dx.doi.org/10.1080/15226514.2016.1207600},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27409290},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27409290},
    day = {13},
    doi = {10.1080/15226514.2016.1207600},
    issn = {1549-7879},
    journal = {International journal of phytoremediation},
    month = jul,
    pmid = {27409290},
    posted-at = {2016-09-24 17:42:27},
    priority = {2},
    title = {Native rhizobia from Zn-mining soil promotes the growth of Leucaena leucocephala on contaminated soil.},
    url = {http://dx.doi.org/10.1080/15226514.2016.1207600},
    year = {2016}
    }

  • J. S. Cristóvão, R. Santos, and C. M. Gomes, “Metals and neuronal metal binding proteins implicated in alzheimer’s disease.,” Oxidative medicine and cellular longevity, vol. 2016, 2016. doi:10.1155/2016/9812178
    [Abstract]

    Alzheimer’s disease ({AD}) is the most prevalent age-related dementia affecting millions of people worldwide. Its main pathological hallmark feature is the formation of insoluble protein deposits of amyloid-β and hyperphosphorylated tau protein into extracellular plaques and intracellular neurofibrillary tangles, respectively. Many of the mechanistic details of this process remain unknown, but a well-established consequence of protein aggregation is synapse dysfunction and neuronal loss in the {AD} brain. Different pathways including mitochondrial dysfunction, oxidative stress, inflammation, and metal metabolism have been suggested to be implicated in this process. In particular, a body of evidence suggests that neuronal metal ions such as copper, zinc, and iron play important roles in brain function in health and disease states and altered homeostasis and distribution as a common feature across different neurodegenerative diseases and aging. In this focused review, we overview neuronal proteins that are involved in {AD} and whose metal binding properties may underlie important biochemical and regulatory processes occurring in the brain during the {AD} pathophysiological process.

    @article{citeulike:14145855,
    abstract = {Alzheimer's disease ({AD}) is the most prevalent age-related dementia affecting millions of people worldwide. Its main pathological hallmark feature is the formation of insoluble protein deposits of amyloid-β and hyperphosphorylated tau protein into extracellular plaques and intracellular neurofibrillary tangles, respectively. Many of the mechanistic details of this process remain unknown, but a well-established consequence of protein aggregation is synapse dysfunction and neuronal loss in the {AD} brain. Different pathways including mitochondrial dysfunction, oxidative stress, inflammation, and metal metabolism have been suggested to be implicated in this process. In particular, a body of evidence suggests that neuronal metal ions such as copper, zinc, and iron play important roles in brain function in health and disease states and altered homeostasis and distribution as a common feature across different neurodegenerative diseases and aging. In this focused review, we overview neuronal proteins that are involved in {AD} and whose metal binding properties may underlie important biochemical and regulatory processes occurring in the brain during the {AD} pathophysiological process.},
    author = {Crist\'{o}v\~{a}o, Joana S. and Santos, Renata and Gomes, Cl\'{a}udio M.},
    citeulike-article-id = {14145855},
    citeulike-linkout-0 = {http://dx.doi.org/10.1155/2016/9812178},
    citeulike-linkout-1 = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736980/},
    citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/26881049},
    citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=26881049},
    doi = {10.1155/2016/9812178},
    issn = {1942-0994},
    journal = {Oxidative medicine and cellular longevity},
    pmcid = {PMC4736980},
    pmid = {26881049},
    posted-at = {2016-09-24 17:41:45},
    priority = {2},
    title = {Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer's Disease.},
    url = {http://dx.doi.org/10.1155/2016/9812178},
    volume = {2016},
    year = {2016}
    }

  • E. Tuncay and B. Turan, “Intracellular zn(2+) increase in cardiomyocytes induces both electrical and mechanical dysfunction in heart via endogenous generation of reactive nitrogen species.,” Biological trace element research, vol. 169, iss. 2, pp. 294-302, 2016. doi:10.1007/s12011-015-0423-3
    [Abstract]

    Oxidants increase intracellular free Zn(2+) concentration ([Zn(2+)]i) in ventricular myocytes, which contributes to oxidant-induced alterations in excitation-contraction coupling ({ECC}). However, it is not clear whether increased [Zn(2+)]i in cardiomyocytes via increased reactive nitrogen species ({RNS}) has a role on heart function under pathological conditions, such as hyperglycemia. In this study, first we aimed to investigate the role of increased [Zn(2+)]i under in vitro condition in the development of both electrical and mechanical dysfunction of isolated papillary muscle strips from rat heart via exposed samples to a Zn(2+)-ionophore (Zn-pyrithione; 1 {μM}) for 20 min. Under simultaneous measurement of intracellular action potential and contractile activity in these preparations, Zn-pyrithione exposure caused marked prolongation in action potential repolarization phase and slowdown in both contraction and relaxation rates of twitch activity. Second, in order to demonstrate an association between increased [Zn(2+)]i and increased {RNS}, we monitored intracellular [Zn(2+)]i under an acute exposure of nitric oxide ({NO}) donor sodium nitroprusside, {SNP}, in freshly isolated quiescent cardiomyocytes loaded with {FluoZin}-3. Resting level of free Zn(2+) is significantly higher in cardiomyocytes under hyperglycemic condition compared to those of the controls, which seems to be associated with increased level of {RNS} production in hyperglycemic cardiomyocytes. Western blot analysis showed that Zn-pyrithione exposure induced a marked decrease in the activity of protein phosphatase 1 and {2A}, member of macromolecular protein complex of cardiac ryanodine receptors, {RyR2}, besides significant increase in the phosphorylation level of extracellular signal-regulated kinase1/2 as a concentration-dependent manner. Overall, the present data demonstrated that there is a cross-relationship between increased {RNS} production and increased [Zn(2+)]i level in cardiomyocytes under pathological conditions such as hyperglycemia.

    @article{citeulike:14145854,
    abstract = {Oxidants increase intracellular free Zn(2+) concentration ([Zn(2+)]i) in ventricular myocytes, which contributes to oxidant-induced alterations in excitation-contraction coupling ({ECC}). However, it is not clear whether increased [Zn(2+)]i in cardiomyocytes via increased reactive nitrogen species ({RNS}) has a role on heart function under pathological conditions, such as hyperglycemia. In this study, first we aimed to investigate the role of increased [Zn(2+)]i under in vitro condition in the development of both electrical and mechanical dysfunction of isolated papillary muscle strips from rat heart via exposed samples to a Zn(2+)-ionophore (Zn-pyrithione; 1 {μM}) for 20 min. Under simultaneous measurement of intracellular action potential and contractile activity in these preparations, Zn-pyrithione exposure caused marked prolongation in action potential repolarization phase and slowdown in both contraction and relaxation rates of twitch activity. Second, in order to demonstrate an association between increased [Zn(2+)]i and increased {RNS}, we monitored intracellular [Zn(2+)]i under an acute exposure of nitric oxide ({NO}) donor sodium nitroprusside, {SNP}, in freshly isolated quiescent cardiomyocytes loaded with {FluoZin}-3. Resting level of free Zn(2+) is significantly higher in cardiomyocytes under hyperglycemic condition compared to those of the controls, which seems to be associated with increased level of {RNS} production in hyperglycemic cardiomyocytes. Western blot analysis showed that Zn-pyrithione exposure induced a marked decrease in the activity of protein phosphatase 1 and {2A}, member of macromolecular protein complex of cardiac ryanodine receptors, {RyR2}, besides significant increase in the phosphorylation level of extracellular signal-regulated kinase1/2 as a concentration-dependent manner. Overall, the present data demonstrated that there is a cross-relationship between increased {RNS} production and increased [Zn(2+)]i level in cardiomyocytes under pathological conditions such as hyperglycemia.},
    author = {Tuncay, Erkan and Turan, Belma},
    citeulike-article-id = {14145854},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s12011-015-0423-3},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26138011},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26138011},
    doi = {10.1007/s12011-015-0423-3},
    issn = {1559-0720},
    journal = {Biological trace element research},
    month = feb,
    number = {2},
    pages = {294--302},
    pmid = {26138011},
    posted-at = {2016-09-24 17:41:04},
    priority = {2},
    title = {Intracellular Zn(2+) Increase in Cardiomyocytes Induces both Electrical and Mechanical Dysfunction in Heart via Endogenous Generation of Reactive Nitrogen Species.},
    url = {http://dx.doi.org/10.1007/s12011-015-0423-3},
    volume = {169},
    year = {2016}
    }

  • D. Billur, E. Tuncay, E. N. N. Okatan, Y. Olgar, A. T. T. Durak, S. Degirmenci, B. Can, and B. Turan, “Interplay between cytosolic free zn(2+) and mitochondrion morphological changes in rat ventricular cardiomyocytes.,” Biological trace element research, 2016. doi:10.1007/s12011-016-0704-5
    [Abstract]

    The Zn(2+) in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum ({S(E})R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of {ZnPO4} (extracellular exposure) or Zn(2+) pyrithione ({ZnPT}) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn(2+) exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in {ZnPO4}- or {ZnPT}-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn(2+)-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during {1-μM} {ZnPT} minute applications by using confocal microscopy. We also showed that {1-μM} {ZnPT} incubation induced significant increases in the phosphorylation levels of {GSK3β} (Ser21 and Ser9), Akt (Ser473), and {NFκB} (Ser276 and Thr254) together with increased expression levels in {ER} stress proteins such as {GRP78} and calregulin. Furthermore, a new key player at {ER}-mitochondria sites, promyelocytic leukemia protein ({PML}) level, was markedly increased in {ZnPT}-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn(2+) can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in {ER}-mitochondria cross talk.

    @article{citeulike:14145850,
    abstract = {The Zn(2+) in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum ({S(E})R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of {ZnPO4} (extracellular exposure) or Zn(2+) pyrithione ({ZnPT}) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn(2+) exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in {ZnPO4}- or {ZnPT}-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn(2+)-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during {1-μM} {ZnPT} minute applications by using confocal microscopy. We also showed that {1-μM} {ZnPT} incubation induced significant increases in the phosphorylation levels of {GSK3β} (Ser21 and Ser9), Akt (Ser473), and {NFκB} (Ser276 and Thr254) together with increased expression levels in {ER} stress proteins such as {GRP78} and calregulin. Furthermore, a new key player at {ER}-mitochondria sites, promyelocytic leukemia protein ({PML}) level, was markedly increased in {ZnPT}-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn(2+) can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in {ER}-mitochondria cross talk.},
    author = {Billur, Deniz and Tuncay, Erkan and Okatan, Esma Nur N. and Olgar, Yusuf and Durak, Aysegul Toy T. and Degirmenci, Sinan and Can, Belgin and Turan, Belma},
    citeulike-article-id = {14145850},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s12011-016-0704-5},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27107885},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27107885},
    day = {23},
    doi = {10.1007/s12011-016-0704-5},
    issn = {1559-0720},
    journal = {Biological trace element research},
    month = apr,
    pmid = {27107885},
    posted-at = {2016-09-24 17:38:48},
    priority = {2},
    title = {Interplay Between Cytosolic Free Zn(2+) and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.},
    url = {http://dx.doi.org/10.1007/s12011-016-0704-5},
    year = {2016}
    }

  • K. Smidt, A. Larsen, A. Br{o}nden, K. S. S{o}rensen, J. V. Nielsen, J. Praetorius, P. M. Martensen, and J. Rungby, “The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression.,” Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, vol. 29, iss. 2, pp. 287-298, 2016. doi:10.1007/s10534-016-9915-7
    [Abstract]

    Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting ({ZNTs}) proteins. The role of different {ZNTs} in the beta cells is currently being clarified. {ZNT8} transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas {ZNT3} knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of {ZNT3} by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of {ZNT3} in a pancreatic beta cell line, {INS}-{1E} overexpressing {ZNT3}. In {INS}-{1E} cells, we found that {ZNT3} was abundant in insulin containing granules located close to the plasma membrane. The level of {ZNT8} {mRNA} was significantly decreased upon over-expression of {ZNT3} at different glucose concentrations (5, 11 and 21 {mM} glucose). {ZNT3} over-expression decreased insulin content and insulin secretion whereas {ZNT3} over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 {mM}). Our data suggest that {ZNT3} and {ZNT8} (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since {mRNA} expression of {ZNT3} was inversely correlated to {ZNT8} and {ZNT3} over-expression reduced insulin synthesis and secretion in {INS}-{1E} cells. {ZNT3} over-expression improved cell survival.

    @article{citeulike:14145847,
    abstract = {Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting ({ZNTs}) proteins. The role of different {ZNTs} in the beta cells is currently being clarified. {ZNT8} transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas {ZNT3} knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of {ZNT3} by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of {ZNT3} in a pancreatic beta cell line, {INS}-{1E} overexpressing {ZNT3}. In {INS}-{1E} cells, we found that {ZNT3} was abundant in insulin containing granules located close to the plasma membrane. The level of {ZNT8} {mRNA} was significantly decreased upon over-expression of {ZNT3} at different glucose concentrations (5, 11 and 21 {mM} glucose). {ZNT3} over-expression decreased insulin content and insulin secretion whereas {ZNT3} over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 {mM}). Our data suggest that {ZNT3} and {ZNT8} (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since {mRNA} expression of {ZNT3} was inversely correlated to {ZNT8} and {ZNT3} over-expression reduced insulin synthesis and secretion in {INS}-{1E} cells. {ZNT3} over-expression improved cell survival.},
    author = {Smidt, Kamille and Larsen, Agnete and Br{\o}nden, Andreas and S{\o}rensen, Karen S. and Nielsen, Julie V. and Praetorius, Jeppe and Martensen, Pia M. and Rungby, J{\o}rgen},
    citeulike-article-id = {14145847},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s10534-016-9915-7},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26867900},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26867900},
    doi = {10.1007/s10534-016-9915-7},
    issn = {1572-8773},
    journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine},
    month = apr,
    number = {2},
    pages = {287--298},
    pmid = {26867900},
    posted-at = {2016-09-24 17:36:41},
    priority = {2},
    title = {The zinc transporter {ZNT3} co-localizes with insulin in {INS}-{1E} pancreatic beta cells and influences cell survival, insulin secretion capacity, and {ZNT8} expression.},
    url = {http://dx.doi.org/10.1007/s10534-016-9915-7},
    volume = {29},
    year = {2016}
    }

  • A. Krężel and W. Maret, “The biological inorganic chemistry of zinc ions.,” Archives of biochemistry and biophysics, 2016. doi:10.1016/j.abb.2016.04.010
    [Abstract]

    The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: {Zn(II}). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10\% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the "mobile" zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide ({ZnO}). In most investigations, reference is made to zinc or Zn(2+) without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn(2+) differs from s-block cations such as Ca(2+) with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is important in zinc biochemistry and for biological recognition as a variety of low molecular weight zinc complexes have already been implicated in biological processes, e.g. with {ATP}, glutathione, citrate, ethylenediaminedisuccinic acid, nicotianamine, or bacillithiol. Copyright {\copyright} 2016 The Authors. Published by Elsevier Inc. All rights reserved.

    @article{citeulike:14145583,
    abstract = {The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: {Zn(II}). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10\% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the "mobile" zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide ({ZnO}). In most investigations, reference is made to zinc or Zn(2+) without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn(2+) differs from s-block cations such as Ca(2+) with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is important in zinc biochemistry and for biological recognition as a variety of low molecular weight zinc complexes have already been implicated in biological processes, e.g. with {ATP}, glutathione, citrate, ethylenediaminedisuccinic acid, nicotianamine, or bacillithiol. Copyright {\copyright} 2016 The Authors. Published by Elsevier Inc. All rights reserved.},
    author = {Krę\.{z}el, Artur and Maret, Wolfgang},
    citeulike-article-id = {14145583},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.abb.2016.04.010},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27117234},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27117234},
    day = {23},
    doi = {10.1016/j.abb.2016.04.010},
    issn = {1096-0384},
    journal = {Archives of biochemistry and biophysics},
    month = apr,
    pmid = {27117234},
    posted-at = {2016-09-24 17:30:20},
    priority = {2},
    title = {The biological inorganic chemistry of zinc ions.},
    url = {http://dx.doi.org/10.1016/j.abb.2016.04.010},
    year = {2016}
    }

  • N. E. Wezynfeld, E. Stefaniak, K. Stachucy, A. Drozd, D. P{l}onka, S. C. Drew, A. Krężel, and W. Bal, “Resistance of Cu(Aβ4-16) to copper capture by metallothionein-3 supports a function for the aβ4-42 peptide as a synaptic Cu(II) scavenger.,” Angewandte chemie (international ed. in english), vol. 55, iss. 29, pp. 8235-8238, 2016. doi:10.1002/anie.201511968
    [Abstract]

    Aβ4-42 is a major species of Aβ peptide in the brains of both healthy individuals and those affected by Alzheimer’s disease. It has recently been demonstrated to bind {Cu(II}) with an affinity approximately 3000 times higher than the commonly studied Aβ1-42 and Aβ1-40 peptides, which are implicated in the pathogenesis of Alzheimer’s disease. Metallothionein-3, a protein considered to orchestrate copper and zinc metabolism in the brain and provide antioxidant protection, was shown to extract {Cu(II}) from Aβ1-40 when acting in its native Zn7 {MT}-3 form. This reaction is assumed to underlie the neuroprotective effect of Zn7 {MT}-3 against Aβ toxicity. In this work, we used the truncated model peptides Aβ1-16 and Aβ4-16 to demonstrate that the high-affinity {Cu(II}) complex of Aβ4-16 is resistant to Zn7 {MT}-3 reactivity. This indicates that the analogous complex of the full-length peptide {Cu(Aβ4}-42) will not yield copper to {MT}-3 in the brain, thus supporting the concept of a physiological role for Aβ4-42 as a {Cu(II}) scavenger in the synaptic cleft. {\copyright} 2016 {WILEY}-{VCH} Verlag {GmbH} & Co. {KGaA}, Weinheim.

    @article{citeulike:14145581,
    abstract = {Aβ4-42 is a major species of Aβ peptide in the brains of both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind {Cu(II}) with an affinity approximately 3000 times higher than the commonly studied Aβ1-42 and Aβ1-40 peptides, which are implicated in the pathogenesis of Alzheimer's disease. Metallothionein-3, a protein considered to orchestrate copper and zinc metabolism in the brain and provide antioxidant protection, was shown to extract {Cu(II}) from Aβ1-40 when acting in its native Zn7 {MT}-3 form. This reaction is assumed to underlie the neuroprotective effect of Zn7 {MT}-3 against Aβ toxicity. In this work, we used the truncated model peptides Aβ1-16 and Aβ4-16 to demonstrate that the high-affinity {Cu(II}) complex of Aβ4-16 is resistant to Zn7 {MT}-3 reactivity. This indicates that the analogous complex of the full-length peptide {Cu(Aβ4}-42) will not yield copper to {MT}-3 in the brain, thus supporting the concept of a physiological role for Aβ4-42 as a {Cu(II}) scavenger in the synaptic cleft. {\copyright} 2016 {WILEY}-{VCH} Verlag {GmbH} \& Co. {KGaA}, Weinheim.},
    author = {Wezynfeld, Nina E. and Stefaniak, Ewelina and Stachucy, Kinga and Drozd, Agnieszka and P{\l}onka, Dawid and Drew, Simon C. and Krę\.{z}el, Artur and Bal, Wojciech},
    citeulike-article-id = {14145581},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/anie.201511968},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27238224},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27238224},
    day = {11},
    doi = {10.1002/anie.201511968},
    issn = {1521-3773},
    journal = {Angewandte Chemie (International ed. in English)},
    month = jul,
    number = {29},
    pages = {8235--8238},
    pmid = {27238224},
    posted-at = {2016-09-24 17:23:45},
    priority = {2},
    title = {Resistance of {Cu(Aβ4}-16) to Copper Capture by Metallothionein-3 Supports a Function for the Aβ4-42 Peptide as a Synaptic {Cu(II}) Scavenger.},
    url = {http://dx.doi.org/10.1002/anie.201511968},
    volume = {55},
    year = {2016}
    }

  • H. Haase, S. Hebel, G. Engelhardt, and L. Rink, “Ethylmercury and hg2+ induce the formation of neutrophil extracellular traps (NETs) by human neutrophil granulocytes.,” Archives of toxicology, vol. 90, iss. 3, pp. 543-550, 2016. doi:10.1007/s00204-015-1484-y
    [Abstract]

    Humans are exposed to different mercurial compounds from various sources, most frequently from dental fillings, preservatives in vaccines, or consumption of fish. Among other toxic effects, these substances interact with the immune system. In high doses, mercurials are immunosuppressive. However, lower doses of some mercurials stimulate the immune system, inducing different forms of autoimmunity, autoantibodies, and glomerulonephritis in rodents. Furthermore, some studies suggest a connection between mercury exposure and the occurrence of autoantibodies against nuclear components and granulocyte cytoplasmic proteins in humans. Still, the underlying mechanisms need to be clarified. The present study investigates the formation of neutrophil extracellular traps ({NETs}) in response to thimerosal and its metabolites ethyl mercury ({EtHg}), thiosalicylic acid, and mercuric ions (Hg(2+)). Only {EtHg} and Hg(2+) triggered {NETosis}. It was independent of {PKC}, {ERK1}/2, p38, and zinc signals and not affected by the {NADPH} oxidase inhibitor {DPI}. Instead, {EtHg} and Hg(2+) triggered {NADPH} oxidase-independent production of {ROS}, which are likely to be involved in mercurial-induced {NET} formation. This finding might help understanding the autoimmune potential of mercurial compounds. Some diseases, to which a connection with mercurials has been shown, such as Wegener’s granulomatosis and systemic lupus erythematosus, are characterized by high prevalence of autoantibodies against neutrophil-specific auto-antigens. Externalization in the form of {NETs} may be a source for exposure to these self-antigens. In genetically susceptible individuals, this could be one step in the series of events leading to autoimmunity.

    @article{citeulike:14145580,
    abstract = {Humans are exposed to different mercurial compounds from various sources, most frequently from dental fillings, preservatives in vaccines, or consumption of fish. Among other toxic effects, these substances interact with the immune system. In high doses, mercurials are immunosuppressive. However, lower doses of some mercurials stimulate the immune system, inducing different forms of autoimmunity, autoantibodies, and glomerulonephritis in rodents. Furthermore, some studies suggest a connection between mercury exposure and the occurrence of autoantibodies against nuclear components and granulocyte cytoplasmic proteins in humans. Still, the underlying mechanisms need to be clarified. The present study investigates the formation of neutrophil extracellular traps ({NETs}) in response to thimerosal and its metabolites ethyl mercury ({EtHg}), thiosalicylic acid, and mercuric ions (Hg(2+)). Only {EtHg} and Hg(2+) triggered {NETosis}. It was independent of {PKC}, {ERK1}/2, p38, and zinc signals and not affected by the {NADPH} oxidase inhibitor {DPI}. Instead, {EtHg} and Hg(2+) triggered {NADPH} oxidase-independent production of {ROS}, which are likely to be involved in mercurial-induced {NET} formation. This finding might help understanding the autoimmune potential of mercurial compounds. Some diseases, to which a connection with mercurials has been shown, such as Wegener's granulomatosis and systemic lupus erythematosus, are characterized by high prevalence of autoantibodies against neutrophil-specific auto-antigens. Externalization in the form of {NETs} may be a source for exposure to these self-antigens. In genetically susceptible individuals, this could be one step in the series of events leading to autoimmunity.},
    author = {Haase, Hajo and Hebel, Silke and Engelhardt, Gabriela and Rink, Lothar},
    citeulike-article-id = {14145580},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00204-015-1484-y},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25701957},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25701957},
    doi = {10.1007/s00204-015-1484-y},
    issn = {1432-0738},
    journal = {Archives of toxicology},
    month = mar,
    number = {3},
    pages = {543--550},
    pmid = {25701957},
    posted-at = {2016-09-24 17:23:24},
    priority = {2},
    title = {Ethylmercury and Hg2+ induce the formation of neutrophil extracellular traps ({NETs}) by human neutrophil granulocytes.},
    url = {http://dx.doi.org/10.1007/s00204-015-1484-y},
    volume = {90},
    year = {2016}
    }

  • R. Hasan, L. Rink, and H. Haase, “Chelation of free zn²⁺ impairs chemotaxis, phagocytosis, oxidative burst, degranulation, and cytokine production by neutrophil granulocytes.,” Biological trace element research, vol. 171, iss. 1, pp. 79-88, 2016. doi:10.1007/s12011-015-0515-0
    [Abstract]

    Neutrophil granulocytes are the largest leukocyte population in the blood and major players in the innate immune response. Impaired neutrophil function has been reported in in vivo studies with zinc-deficient human subjects and experimental animals. Moreover, in vitro formation of neutrophil extracellular traps has been shown to depend on free intracellular Zn(2+). This study investigates the requirement of Zn(2+) for several other essential neutrophil functions, such as chemotaxis, phagocytosis, cytokine production, and degranulation. To exclude artifacts resulting from indirect effects of zinc deprivation, such as impaired hematopoietic development and influences of other immune cells, direct effects of zinc deprivation were tested in vitro using cells isolated from healthy human donors. Chelation of Zn(2+) by the membrane permeable chelator {N,N},{N’,N}’-tetrakis-(2-pyridylmethyl)-ethylenediamine ({TPEN}) reduced granulocyte migration toward {N-formyl-L}-{methionyl-L}-{leucyl-L}-phenylalanine ({fMLF}) and {IL}-8, indicating a role of free intracellular Zn(2+) in chemotaxis. However, a direct action of Zn(2+) as a chemoattractant, as previously reported by others, was not observed. Similar to chemotaxis, phagocytosis, oxidative burst, and granule release were also impaired in {TPEN}-treated granulocytes. Moreover, Zn(2+) contributes to the regulatory role of neutrophil granulocytes in the inflammatory response by affecting the cytokine production by these cells. {TPEN} inhibited the lipopolysaccharide-induced secretion of chemotactic {IL}-8 and also anti-inflammatory {IL}-1ra. In conclusion, free intracellular Zn(2+) plays essential roles in multiple neutrophil functions, affecting extravasation to the site of the infection, uptake and killing of microorganisms, and inflammation.

    @article{citeulike:14145578,
    abstract = {Neutrophil granulocytes are the largest leukocyte population in the blood and major players in the innate immune response. Impaired neutrophil function has been reported in in vivo studies with zinc-deficient human subjects and experimental animals. Moreover, in vitro formation of neutrophil extracellular traps has been shown to depend on free intracellular Zn(2+). This study investigates the requirement of Zn(2+) for several other essential neutrophil functions, such as chemotaxis, phagocytosis, cytokine production, and degranulation. To exclude artifacts resulting from indirect effects of zinc deprivation, such as impaired hematopoietic development and influences of other immune cells, direct effects of zinc deprivation were tested in vitro using cells isolated from healthy human donors. Chelation of Zn(2+) by the membrane permeable chelator {N,N},{N',N}'-tetrakis-(2-pyridylmethyl)-ethylenediamine ({TPEN}) reduced granulocyte migration toward {N-formyl-L}-{methionyl-L}-{leucyl-L}-phenylalanine ({fMLF}) and {IL}-8, indicating a role of free intracellular Zn(2+) in chemotaxis. However, a direct action of Zn(2+) as a chemoattractant, as previously reported by others, was not observed. Similar to chemotaxis, phagocytosis, oxidative burst, and granule release were also impaired in {TPEN}-treated granulocytes. Moreover, Zn(2+) contributes to the regulatory role of neutrophil granulocytes in the inflammatory response by affecting the cytokine production by these cells. {TPEN} inhibited the lipopolysaccharide-induced secretion of chemotactic {IL}-8 and also anti-inflammatory {IL}-1ra. In conclusion, free intracellular Zn(2+) plays essential roles in multiple neutrophil functions, affecting extravasation to the site of the infection, uptake and killing of microorganisms, and inflammation.},
    author = {Hasan, Rafah and Rink, Lothar and Haase, Hajo},
    citeulike-article-id = {14145578},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s12011-015-0515-0},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26400651},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26400651},
    doi = {10.1007/s12011-015-0515-0},
    issn = {1559-0720},
    journal = {Biological trace element research},
    month = may,
    number = {1},
    pages = {79--88},
    pmid = {26400651},
    posted-at = {2016-09-24 17:20:59},
    priority = {2},
    title = {Chelation of Free Zn²⁺ Impairs Chemotaxis, Phagocytosis, Oxidative Burst, Degranulation, and Cytokine Production by Neutrophil Granulocytes.},
    url = {http://dx.doi.org/10.1007/s12011-015-0515-0},
    volume = {171},
    year = {2016}
    }

  • E. Rosenkranz, C. H. Metz, M. Maywald, R. D. Hilgers, I. Weßels, T. Senff, H. Haase, M. Jäger, M. Ott, R. Aspinall, B. Plümäkers, and L. Rink, “Zinc supplementation induces regulatory t cells by inhibition of sirt-1 deacetylase in mixed lymphocyte cultures.,” Molecular nutrition & food research, vol. 60, iss. 3, pp. 661-671, 2016. doi:10.1002/mnfr.201500524
    [Abstract]

    Zinc is an essential trace element, regulating immune function. Its deficiency results in immune dysfunction and transplant rejection. In here, a benefit of zinc supplementation for the induction of tolerance was investigated, focusing on the {TH} 1-dominated allogeneic immune reaction. Allogeneic immune reaction was modeled by mixed lymphocyte culture ({MLC}). The effect of zinc supplementation was monitored via expression of cytokines and surface lineage markers using {ELISA} and flow cytometry. Epigenetic analyses were performed to investigate mechanisms underlying zinc-induced changes in regulatory T cell (Treg) activation. Results reveal that Tregs are induced when {MLCs} are treated with 50 {μM} zinc causing a decrease in {IFNγ} production. {IL}-2 and {IL}-10 expression were not affected. The teleology of this effect includes the inhibition of histone deacetylase Sirt-1-mediated Foxp3 deacetylation, resulting in its decreased degradation. In conclusion, zinc should be considered to prevent graft-versus-host disease ({GVHD}) as it is capable of stabilizing {iTregs}, resulting in increased numbers of this cell type while not suppressing the immune system. {\copyright} 2015 {WILEY}-{VCH} Verlag {GmbH} & Co. {KGaA}, Weinheim.

    @article{citeulike:14145363,
    abstract = {Zinc is an essential trace element, regulating immune function. Its deficiency results in immune dysfunction and transplant rejection. In here, a benefit of zinc supplementation for the induction of tolerance was investigated, focusing on the {TH} 1-dominated allogeneic immune reaction. Allogeneic immune reaction was modeled by mixed lymphocyte culture ({MLC}). The effect of zinc supplementation was monitored via expression of cytokines and surface lineage markers using {ELISA} and flow cytometry. Epigenetic analyses were performed to investigate mechanisms underlying zinc-induced changes in regulatory T cell (Treg) activation. Results reveal that Tregs are induced when {MLCs} are treated with 50 {μM} zinc causing a decrease in {IFNγ} production. {IL}-2 and {IL}-10 expression were not affected. The teleology of this effect includes the inhibition of histone deacetylase Sirt-1-mediated Foxp3 deacetylation, resulting in its decreased degradation. In conclusion, zinc should be considered to prevent graft-versus-host disease ({GVHD}) as it is capable of stabilizing {iTregs}, resulting in increased numbers of this cell type while not suppressing the immune system. {\copyright} 2015 {WILEY}-{VCH} Verlag {GmbH} \& Co. {KGaA}, Weinheim.},
    author = {Rosenkranz, Eva and Metz, Claudia H. and Maywald, Martina and Hilgers, Ralf-Dieter D. and We{\ss}els, Inga and Senff, Tina and Haase, Hajo and J\"{a}ger, Maximilian and Ott, Melanie and Aspinall, Richard and Pl\"{u}m\"{a}kers, Birgit and Rink, Lothar},
    citeulike-article-id = {14145363},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/mnfr.201500524},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26614004},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26614004},
    doi = {10.1002/mnfr.201500524},
    issn = {1613-4133},
    journal = {Molecular nutrition \& food research},
    month = mar,
    number = {3},
    pages = {661--671},
    pmid = {26614004},
    posted-at = {2016-09-23 22:12:26},
    priority = {2},
    title = {Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures.},
    url = {http://dx.doi.org/10.1002/mnfr.201500524},
    volume = {60},
    year = {2016}
    }

  • K. Ariaans, N. Heussen, H. Schiffer, A. L. Wienert, B. Plümäkers, L. Rink, and S. Wolfart, “Use of molecular indicators of inflammation to assess the biocompatibility of all-ceramic restorations.,” Journal of clinical periodontology, vol. 43, iss. 2, pp. 173-179, 2016. doi:10.1111/jcpe.12500
    [Abstract]

    The purpose of this in vivo study was quantification of inflammatory reaction to ceramic restorations made from lithium disilicate and zirconia by measurement of the concentration of indicators of inflammation in the gingival crevicular fluid ({GCF}). Patients out of three prospective cohort-studies investigating three different all-ceramic restoration materials for crowns and fixed dental prostheses were included. Patients needed an associated, unrestored tooth to serve as control. {GCF} samples were taken from the sulcus of the restored teeth and the related controls (n = 59 pairs) and the concentrations of {IL1}-beta, {IL}-1ra and {aMMP}-8, as indicators of inflammation, were determined by use of {ELISA} tests. Periodontal status was also assessed clinically by measurement of pocket depth ({PD}), plaque index ({PI}) and bleeding on probing ({BOP}). The concentrations of the inflammation indicators were not significantly different between restored teeth and controls or between lithium disilicate and zirconia restorations (p > 0.05). Furthermore, no significant difference between {PD} of restored teeth and controls or between groups could be shown. Within the limitation of the study, treatment with all-ceramic restorations did not induce inflammatory reactions in a group of periodontal healthy patients. No differences between the gingiva reactions of lithium disilicate and zirconia restorations could be shown. {\copyright} 2015 John Wiley & Sons {A/S}. Published by John Wiley & Sons Ltd.

    @article{citeulike:14145361,
    abstract = {The purpose of this in vivo study was quantification of inflammatory reaction to ceramic restorations made from lithium disilicate and zirconia by measurement of the concentration of indicators of inflammation in the gingival crevicular fluid ({GCF}). Patients out of three prospective cohort-studies investigating three different all-ceramic restoration materials for crowns and fixed dental prostheses were included. Patients needed an associated, unrestored tooth to serve as control. {GCF} samples were taken from the sulcus of the restored teeth and the related controls (n = 59 pairs) and the concentrations of {IL1}-beta, {IL}-1ra and {aMMP}-8, as indicators of inflammation, were determined by use of {ELISA} tests. Periodontal status was also assessed clinically by measurement of pocket depth ({PD}), plaque index ({PI}) and bleeding on probing ({BOP}). The concentrations of the inflammation indicators were not significantly different between restored teeth and controls or between lithium disilicate and zirconia restorations (p > 0.05). Furthermore, no significant difference between {PD} of restored teeth and controls or between groups could be shown. Within the limitation of the study, treatment with all-ceramic restorations did not induce inflammatory reactions in a group of periodontal healthy patients. No differences between the gingiva reactions of lithium disilicate and zirconia restorations could be shown. {\copyright} 2015 John Wiley \& Sons {A/S}. Published by John Wiley \& Sons Ltd.},
    author = {Ariaans, Kirsten and Heussen, Nicole and Schiffer, Hanna and Wienert, Anna-Lena L. and Pl\"{u}m\"{a}kers, Birgit and Rink, Lothar and Wolfart, Stefan},
    citeulike-article-id = {14145361},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/jcpe.12500},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26714449},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26714449},
    doi = {10.1111/jcpe.12500},
    issn = {1600-051X},
    journal = {Journal of clinical periodontology},
    month = feb,
    number = {2},
    pages = {173--179},
    pmid = {26714449},
    posted-at = {2016-09-23 22:10:32},
    priority = {2},
    title = {Use of molecular indicators of inflammation to assess the biocompatibility of all-ceramic restorations.},
    url = {http://dx.doi.org/10.1111/jcpe.12500},
    volume = {43},
    year = {2016}
    }

  • E. Rosenkranz, M. Maywald, R. D. Hilgers, A. Brieger, T. Clarner, M. Kipp, B. Plümäkers, S. Meyer, T. Schwerdtle, and L. Rink, “Induction of regulatory t cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration.,” The journal of nutritional biochemistry, vol. 29, pp. 116-123, 2016. doi:10.1016/j.jnutbio.2015.11.010
    [Abstract]

    The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 μg/day (0.3mg/kg body weight) or 30 μg/day (1.5mg/kg body weight) on murine experimental autoimmune encephalomyelitis ({EAE}), an animal model for multiple sclerosis with a {Th1/Th17} (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished {EAE} scores in {C57BL}/6 mice in vivo (P<.05), reduced Th17 {RORγT}(+) cells (P<.05) and significantly increased inducible {iTreg} cells (P<.05). While Th17 cells decreased systemically, {iTreg} cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing {iTreg} cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system. Copyright {\copyright} 2015 Elsevier Inc. All rights reserved.

    @article{citeulike:14145340,
    abstract = {The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 μg/day (0.3mg/kg body weight) or 30 μg/day (1.5mg/kg body weight) on murine experimental autoimmune encephalomyelitis ({EAE}), an animal model for multiple sclerosis with a {Th1/Th17} (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished {EAE} scores in {C57BL}/6 mice in vivo (P<.05), reduced Th17 {RORγT}(+) cells (P<.05) and significantly increased inducible {iTreg} cells (P<.05). While Th17 cells decreased systemically, {iTreg} cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing {iTreg} cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system. Copyright {\copyright} 2015 Elsevier Inc. All rights reserved.},
    author = {Rosenkranz, Eva and Maywald, Martina and Hilgers, Ralf-Dieter D. and Brieger, Anne and Clarner, Tim and Kipp, Markus and Pl\"{u}m\"{a}kers, Birgit and Meyer, S\"{o}ren and Schwerdtle, Tanja and Rink, Lothar},
    citeulike-article-id = {14145340},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jnutbio.2015.11.010},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26895672},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26895672},
    doi = {10.1016/j.jnutbio.2015.11.010},
    issn = {1873-4847},
    journal = {The Journal of nutritional biochemistry},
    month = mar,
    pages = {116--123},
    pmid = {26895672},
    posted-at = {2016-09-23 20:58:52},
    priority = {2},
    title = {Induction of regulatory T cells in {Th1-/Th17}-driven experimental autoimmune encephalomyelitis by zinc administration.},
    url = {http://dx.doi.org/10.1016/j.jnutbio.2015.11.010},
    volume = {29},
    year = {2016}
    }

  • J. E. E. Kessels, I. Wessels, H. Haase, L. Rink, and P. Uciechowski, “Influence of DNA-methylation on zinc homeostasis in myeloid cells: regulation of zinc transporters and zinc binding proteins.,” Journal of trace elements in medicine and biology : organ of the society for minerals and trace elements (gms), vol. 37, pp. 125-133, 2016. doi:10.1016/j.jtemb.2016.02.003
    [Abstract]

    The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as {DNA} methylation are involved in the expression of these genes. In demethylation experiments using {5-Aza}-2′-deoxycytidine ({AZA}) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line {HL}-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after {DNA} demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time {PCR} analyses of 14 {ZIP} (solute-linked carrier ({SLC}) {SLC39A}; {Zrt/IRT}-like protein), and 9 {ZnT} ({SLC30A}) zinc transporters revealed significantly enhanced {mRNA} expression of the zinc importer {ZIP1} after {AZA} treatment. Because {ZIP1} protein was also enhanced after {AZA} treatment, {ZIP1} up-regulation might be the mediator of enhanced intracellular zinc levels. The {mRNA} expression of {ZIP14} was decreased, whereas zinc exporter {ZnT3} {mRNA} was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of {ZIP1} promoter region I was detected by chromatin accessibility by real-time {PCR} ({CHART}) assays after demethylation. Additionally, {DNA} demethylation resulted in increased {mRNA} accumulation of zinc binding proteins metallothionein ({MT}) and {S100A8}/{S100A9} after 48h. {MT} {mRNA} was significantly enhanced after 24h of {AZA} treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that {DNA} methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright {\copyright} 2016 Elsevier {GmbH}. All rights reserved.

    @article{citeulike:14145339,
    abstract = {The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as {DNA} methylation are involved in the expression of these genes. In demethylation experiments using {5-Aza}-2'-deoxycytidine ({AZA}) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line {HL}-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after {DNA} demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time {PCR} analyses of 14 {ZIP} (solute-linked carrier ({SLC}) {SLC39A}; {Zrt/IRT}-like protein), and 9 {ZnT} ({SLC30A}) zinc transporters revealed significantly enhanced {mRNA} expression of the zinc importer {ZIP1} after {AZA} treatment. Because {ZIP1} protein was also enhanced after {AZA} treatment, {ZIP1} up-regulation might be the mediator of enhanced intracellular zinc levels. The {mRNA} expression of {ZIP14} was decreased, whereas zinc exporter {ZnT3} {mRNA} was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of {ZIP1} promoter region I was detected by chromatin accessibility by real-time {PCR} ({CHART}) assays after demethylation. Additionally, {DNA} demethylation resulted in increased {mRNA} accumulation of zinc binding proteins metallothionein ({MT}) and {S100A8}/{S100A9} after 48h. {MT} {mRNA} was significantly enhanced after 24h of {AZA} treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that {DNA} methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright {\copyright} 2016 Elsevier {GmbH}. All rights reserved.},
    author = {Kessels, Jana Elena E. and Wessels, Inga and Haase, Hajo and Rink, Lothar and Uciechowski, Peter},
    citeulike-article-id = {14145339},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jtemb.2016.02.003},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26905204},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26905204},
    doi = {10.1016/j.jtemb.2016.02.003},
    issn = {1878-3252},
    journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
    month = sep,
    pages = {125--133},
    pmid = {26905204},
    posted-at = {2016-09-23 20:40:13},
    priority = {2},
    title = {Influence of {DNA}-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.},
    url = {http://dx.doi.org/10.1016/j.jtemb.2016.02.003},
    volume = {37},
    year = {2016}
    }

  • M. Maywald and L. Rink, “Zinc supplementation induces CD4(+)CD25(+)foxp3(+) antigen-specific regulatory t cells and suppresses IFN-γ production by upregulation of foxp3 and KLF-10 and downregulation of IRF-1.,” European journal of nutrition, 2016. doi:10.1007/s00394-016-1228-7
    [Abstract]

    The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures ({MLC}), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [({3)H}]-thymidine proliferation assay and {ELISA}, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and {mRNA} analysis were used for Foxp3, {KLF}-10, and {IRF}-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 {µM}) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on {MLC} results in an increased induction and stabilization of {CD4}(+){CD25}(+)Foxp3(+) and {CD4}(+){CD25}(+){CTLA}-4(+) T cells (p < 0.05). The effect is based on zinc-induced upregulation of Foxp3 and {KLF}-10 and downregulation of {IRF}-1. However, in resting lymphocytes zinc increases {IRF}-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific {iTreg} cells due to modulation of essential molecular targets: Foxp3, {KLF}-10, and {IRF}-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.

    @article{citeulike:14145337,
    abstract = {The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures ({MLC}), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [({3)H}]-thymidine proliferation assay and {ELISA}, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and {mRNA} analysis were used for Foxp3, {KLF}-10, and {IRF}-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 {µM}) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on {MLC} results in an increased induction and stabilization of {CD4}(+){CD25}(+)Foxp3(+) and {CD4}(+){CD25}(+){CTLA}-4(+) T cells (p < 0.05). The effect is based on zinc-induced upregulation of Foxp3 and {KLF}-10 and downregulation of {IRF}-1. However, in resting lymphocytes zinc increases {IRF}-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific {iTreg} cells due to modulation of essential molecular targets: Foxp3, {KLF}-10, and {IRF}-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.},
    author = {Maywald, Martina and Rink, Lothar},
    citeulike-article-id = {14145337},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00394-016-1228-7},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27260002},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27260002},
    day = {3},
    doi = {10.1007/s00394-016-1228-7},
    issn = {1436-6215},
    journal = {European journal of nutrition},
    month = jun,
    pmid = {27260002},
    posted-at = {2016-09-23 20:24:07},
    priority = {2},
    title = {Zinc supplementation induces {CD4}(+){CD25}(+)Foxp3(+) antigen-specific regulatory T cells and suppresses {IFN}-γ production by upregulation of Foxp3 and {KLF}-10 and downregulation of {IRF}-1.},
    url = {http://dx.doi.org/10.1007/s00394-016-1228-7},
    year = {2016}
    }

  • J. C. King, K. H. Brown, R. S. Gibson, N. F. Krebs, N. M. Lowe, J. H. Siekmann, and D. J. Raiten, “Biomarkers of nutrition for development (BOND)-zinc review.,” The journal of nutrition, 2016. doi:10.3945/jn.115.229708
    [Abstract]

    Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The {BOND} (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration ({PZC}), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. {PZCs} respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. {PZC} cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the {PZC} to assess zinc status. {PZCs} respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in {PZCs} with changes in dietary zinc, and {PZCs} are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or {DNA} damage. {\copyright} 2016 American Society for Nutrition.

    @article{citeulike:14145335,
    abstract = {Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The {BOND} (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration ({PZC}), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. {PZCs} respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. {PZC} cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the {PZC} to assess zinc status. {PZCs} respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in {PZCs} with changes in dietary zinc, and {PZCs} are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or {DNA} damage. {\copyright} 2016 American Society for Nutrition.},
    author = {King, Janet C. and Brown, Kenneth H. and Gibson, Rosalind S. and Krebs, Nancy F. and Lowe, Nicola M. and Siekmann, Jonathan H. and Raiten, Daniel J.},
    citeulike-article-id = {14145335},
    citeulike-linkout-0 = {http://dx.doi.org/10.3945/jn.115.229708},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26962190},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26962190},
    day = {9},
    doi = {10.3945/jn.115.229708},
    issn = {1541-6100},
    journal = {The Journal of nutrition},
    month = mar,
    pmid = {26962190},
    posted-at = {2016-09-23 20:23:41},
    priority = {2},
    title = {Biomarkers of Nutrition for Development ({BOND})-Zinc Review.},
    url = {http://dx.doi.org/10.3945/jn.115.229708},
    year = {2016}
    }

  • R. S. Gibson, J. C. King, and N. Lowe, “A review of dietary zinc recommendations.,” Food and nutrition bulletin, 2016. doi:10.1177/0379572116652252
    [Abstract]

    Large discrepancies exist among the dietary zinc recommendations set by expert groups. To describe the basis for the differences in the dietary zinc recommendations set by the World Health Organization, the {US} Institute of Medicine, the International Zinc Nutrition Consultative Group, and the European Food Safety Agency. We compared the sources of the data, the concepts, and methods used by the 4 expert groups to set the physiological requirements for absorbed zinc, the dietary zinc requirements (termed estimated and/or average requirements), recommended dietary allowances (or recommended nutrient intakes or population reference intakes), and tolerable upper intake levels for selected age, sex, and life-stage groups. All 4 expert groups used the factorial approach to estimate the physiological requirements for zinc. These are based on the estimates of absorbed zinc required to offset all obligatory zinc losses plus any additional requirements for absorbed zinc for growth, pregnancy, or lactation. However, discrepancies exist in the reference body weights used, studies selected, approaches to estimate endogenous fecal zinc ({EFZ}) losses, the adjustments applied to derive dietary zinc requirements that take into account zinc bioavailability in the habitual diets, number of dietary zinc recommendations set, and the nomenclature used to describe them. Estimates for the physiological and dietary requirements varied across the 4 expert groups. The European Food Safety Agency was the only expert group that set dietary zinc recommendations at 4 different levels of dietary phytate for adults (but not for children) and as of yet no tolerable upper intake level for any life-stage group. {\copyright} The Author(s) 2016.

    @article{citeulike:14145334,
    abstract = {Large discrepancies exist among the dietary zinc recommendations set by expert groups. To describe the basis for the differences in the dietary zinc recommendations set by the World Health Organization, the {US} Institute of Medicine, the International Zinc Nutrition Consultative Group, and the European Food Safety Agency. We compared the sources of the data, the concepts, and methods used by the 4 expert groups to set the physiological requirements for absorbed zinc, the dietary zinc requirements (termed estimated and/or average requirements), recommended dietary allowances (or recommended nutrient intakes or population reference intakes), and tolerable upper intake levels for selected age, sex, and life-stage groups. All 4 expert groups used the factorial approach to estimate the physiological requirements for zinc. These are based on the estimates of absorbed zinc required to offset all obligatory zinc losses plus any additional requirements for absorbed zinc for growth, pregnancy, or lactation. However, discrepancies exist in the reference body weights used, studies selected, approaches to estimate endogenous fecal zinc ({EFZ}) losses, the adjustments applied to derive dietary zinc requirements that take into account zinc bioavailability in the habitual diets, number of dietary zinc recommendations set, and the nomenclature used to describe them. Estimates for the physiological and dietary requirements varied across the 4 expert groups. The European Food Safety Agency was the only expert group that set dietary zinc recommendations at 4 different levels of dietary phytate for adults (but not for children) and as of yet no tolerable upper intake level for any life-stage group. {\copyright} The Author(s) 2016.},
    author = {Gibson, Rosalind S. and King, Janet C. and Lowe, Nicola},
    citeulike-article-id = {14145334},
    citeulike-linkout-0 = {http://dx.doi.org/10.1177/0379572116652252},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27312357},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27312357},
    day = {16},
    doi = {10.1177/0379572116652252},
    issn = {1564-8265},
    journal = {Food and nutrition bulletin},
    month = jun,
    pmid = {27312357},
    posted-at = {2016-09-23 20:23:26},
    priority = {2},
    title = {A Review of Dietary Zinc Recommendations.},
    url = {http://dx.doi.org/10.1177/0379572116652252},
    year = {2016}
    }

  • N. M. Lowe, “Assessing zinc in humans.,” Current opinion in clinical nutrition and metabolic care, 2016. doi:10.1097/MCO.0000000000000298
    [Abstract]

    To examine the most recent literature that provides new data regarding the potential and emerging biomarkers for zinc status in individuals. Suboptimal dietary zinc intake is estimated to affect 17\% of the world’s population; however, the assessment of zinc status is notoriously difficult. A systematic review and meta-analysis of studies investigating biochemical biomarkers of zinc status was conducted by the European Micronutrient Recommendations Aligned network. This review summarized the data published from inception to 2007. More recently (2016), an international expert panel, convened by the biomarker of nutrition for development initiative, published an extensive review of the literature addressing biomarkers of zinc status in populations and individuals and categorized the biomarkers as useful [dietary intake, serum Zn concentration and stunting], potentially useful [hair Zn concentration, urine Zn concentration and neurobehavioural function] and emerging [nail Zn concentration, oxidative stress and {DNA} integrity, zinc kinetics, zinc-dependent proteins and taste acuity]. The most recent data on the potentially useful biomarkers support the further investigation of hair Zn concentration and indices of neurological function, particularly those assessing memory and attention. Of the emerging biomarkers, the measurement of {DNA} integrity and the expression of zinc transport proteins look promising.

    @article{citeulike:14145333,
    abstract = {To examine the most recent literature that provides new data regarding the potential and emerging biomarkers for zinc status in individuals. Suboptimal dietary zinc intake is estimated to affect 17\% of the world's population; however, the assessment of zinc status is notoriously difficult. A systematic review and meta-analysis of studies investigating biochemical biomarkers of zinc status was conducted by the European Micronutrient Recommendations Aligned network. This review summarized the data published from inception to 2007. More recently (2016), an international expert panel, convened by the biomarker of nutrition for development initiative, published an extensive review of the literature addressing biomarkers of zinc status in populations and individuals and categorized the biomarkers as useful [dietary intake, serum Zn concentration and stunting], potentially useful [hair Zn concentration, urine Zn concentration and neurobehavioural function] and emerging [nail Zn concentration, oxidative stress and {DNA} integrity, zinc kinetics, zinc-dependent proteins and taste acuity]. The most recent data on the potentially useful biomarkers support the further investigation of hair Zn concentration and indices of neurological function, particularly those assessing memory and attention. Of the emerging biomarkers, the measurement of {DNA} integrity and the expression of zinc transport proteins look promising.},
    author = {Lowe, Nicola M.},
    citeulike-article-id = {14145333},
    citeulike-linkout-0 = {http://dx.doi.org/10.1097/MCO.0000000000000298},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/27348152},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=27348152},
    day = {24},
    doi = {10.1097/MCO.0000000000000298},
    issn = {1473-6519},
    journal = {Current opinion in clinical nutrition and metabolic care},
    month = jun,
    pmid = {27348152},
    posted-at = {2016-09-23 20:23:11},
    priority = {2},
    title = {Assessing zinc in humans.},
    url = {http://dx.doi.org/10.1097/MCO.0000000000000298},
    year = {2016}
    }

2015

  • J. Janssen, N. Weyens, S. Croes, B. Beckers, L. Meiresonne, P. Van Peteghem, R. Carleer, and J. Vangronsveld, “Phytoremediation of metal contaminated soil using willow: exploiting Plant-Associated bacteria to improve biomass production and metal uptake.,” International journal of phytoremediation, vol. 17, iss. 11, pp. 1123-1136, 2015. doi:10.1080/15226514.2015.1045129
    [Abstract]

    Short rotation coppice ({SRC}) of willow and poplar is proposed for economic valorization and concurrently as remediation strategy for metal contaminated land in {northeast-Belgium}. However, metal phytoextraction appears insufficient to effectuate rapid reduction of soil metal contents. To increase both biomass production and metal accumulation of {SRC}, two strategies are proposed: (i) in situ selection of the best performing clones and (ii) bioaugmentation of these clones with beneficial plant-associated bacteria. Based on field data, two experimental willow clones, a Salix viminalis and a Salix alba x alba clone, were selected. Compared to the best performing commercial clones, considerable increases in stem metal extraction were achieved (up to 74\% for Cd and 91\% for Zn). From the selected clones, plant-associated bacteria were isolated and identified. All strains were subsequently screened for their plant growth-promoting and metal uptake enhancing traits. Five strains were selected for a greenhouse inoculation experiment with the selected clones planted in {Cd-Zn}-Pb contaminated soil. Extraction potential tended to increase after inoculation of S. viminalis plants with a Rahnella sp. strain due to a significantly increased twig biomass. However, although bacterial strains showing beneficial traits in vitro were used for inoculation, increments in extraction potential were not always observed.

    @article{citeulike:14145883,
    abstract = {Short rotation coppice ({SRC}) of willow and poplar is proposed for economic valorization and concurrently as remediation strategy for metal contaminated land in {northeast-Belgium}. However, metal phytoextraction appears insufficient to effectuate rapid reduction of soil metal contents. To increase both biomass production and metal accumulation of {SRC}, two strategies are proposed: (i) in situ selection of the best performing clones and (ii) bioaugmentation of these clones with beneficial plant-associated bacteria. Based on field data, two experimental willow clones, a Salix viminalis and a Salix alba x alba clone, were selected. Compared to the best performing commercial clones, considerable increases in stem metal extraction were achieved (up to 74\% for Cd and 91\% for Zn). From the selected clones, plant-associated bacteria were isolated and identified. All strains were subsequently screened for their plant growth-promoting and metal uptake enhancing traits. Five strains were selected for a greenhouse inoculation experiment with the selected clones planted in {Cd-Zn}-Pb contaminated soil. Extraction potential tended to increase after inoculation of S. viminalis plants with a Rahnella sp. strain due to a significantly increased twig biomass. However, although bacterial strains showing beneficial traits in vitro were used for inoculation, increments in extraction potential were not always observed.},
    author = {Janssen, Jolien and Weyens, Nele and Croes, Sarah and Beckers, Bram and Meiresonne, Linda and Van Peteghem, Pierre and Carleer, Robert and Vangronsveld, Jaco},
    citeulike-article-id = {14145883},
    citeulike-linkout-0 = {http://dx.doi.org/10.1080/15226514.2015.1045129},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25942689},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25942689},
    doi = {10.1080/15226514.2015.1045129},
    issn = {1549-7879},
    journal = {International journal of phytoremediation},
    number = {11},
    pages = {1123--1136},
    pmid = {25942689},
    posted-at = {2016-09-24 18:13:05},
    priority = {2},
    title = {Phytoremediation of Metal Contaminated Soil Using Willow: Exploiting {Plant-Associated} Bacteria to Improve Biomass Production and Metal Uptake.},
    url = {http://dx.doi.org/10.1080/15226514.2015.1045129},
    volume = {17},
    year = {2015}
    }

  • A. Lehotzky, J. Oláh, S. Szunyogh, A. Szabó, T. Berki, and J. Ovádi, “Zinc-induced structural changes of the disordered tppp/p25 inhibits its degradation by the proteasome.,” Biochimica et biophysica acta, vol. 1852, iss. 1, pp. 83-91, 2015. doi:10.1016/j.bbadis.2014.10.015
    [Abstract]

    Tubulin Polymerization Promoting Protein/p25 ({TPPP}/p25), a neomorphic moonlighting protein displaying both physiological and pathological functions, plays a crucial role in the differentiation of the zinc-rich oligodendrocytes, the major constituent of myelin sheath; and it is enriched and co-localizes with α-synuclein in brain inclusions hallmarking Parkinson’s disease and other synucleinopathies. In this work we showed that the binding of Zn(2+) to {TPPP}/p25 promotes its dimerization resulting in increased tubulin polymerization promoting activity. We also demonstrated that the Zn(2+) increases the intracellular {TPPP}/p25 level resulting in a more decorated microtubule network in {CHO10} and {CG}-4 cells expressing {TPPP}/p25 ectopically and endogenously, respectively. This stabilization effect is crucial for the differentiation and aggresome formation under physiological and pathological conditions, respectively. The Zn(2+)-mediated effect was similar to that produced by treatment of the cells with {MG132}, a proteasome inhibitor or Zn(2+) plus {MG132} as quantified by cellular {ELISA}. The enhancing effect of zinc ion on the level of {TPPP}/p25 was independent of the expression level of the protein produced by doxycycline induction at different levels or inhibition of the protein synthesis by cycloheximide. Thus, we suggest that the zinc as a specific divalent cation could be involved in the fine-tuning of the physiological {TPPP}/p25 level counteracting both the enrichment and the lack of this protein leading to distinct central nervous system diseases. Copyright {\copyright} 2014. Published by Elsevier {B.V}.

    @article{citeulike:14145876,
    abstract = {Tubulin Polymerization Promoting Protein/p25 ({TPPP}/p25), a neomorphic moonlighting protein displaying both physiological and pathological functions, plays a crucial role in the differentiation of the zinc-rich oligodendrocytes, the major constituent of myelin sheath; and it is enriched and co-localizes with α-synuclein in brain inclusions hallmarking Parkinson's disease and other synucleinopathies. In this work we showed that the binding of Zn(2+) to {TPPP}/p25 promotes its dimerization resulting in increased tubulin polymerization promoting activity. We also demonstrated that the Zn(2+) increases the intracellular {TPPP}/p25 level resulting in a more decorated microtubule network in {CHO10} and {CG}-4 cells expressing {TPPP}/p25 ectopically and endogenously, respectively. This stabilization effect is crucial for the differentiation and aggresome formation under physiological and pathological conditions, respectively. The Zn(2+)-mediated effect was similar to that produced by treatment of the cells with {MG132}, a proteasome inhibitor or Zn(2+) plus {MG132} as quantified by cellular {ELISA}. The enhancing effect of zinc ion on the level of {TPPP}/p25 was independent of the expression level of the protein produced by doxycycline induction at different levels or inhibition of the protein synthesis by cycloheximide. Thus, we suggest that the zinc as a specific divalent cation could be involved in the fine-tuning of the physiological {TPPP}/p25 level counteracting both the enrichment and the lack of this protein leading to distinct central nervous system diseases. Copyright {\copyright} 2014. Published by Elsevier {B.V}.},
    author = {Lehotzky, Attila and Ol\'{a}h, Judit and Szunyogh, S\'{a}ndor and Szab\'{o}, Ad\'{e}l and Berki, T\'{\i}mea and Ov\'{a}di, Judit},
    citeulike-article-id = {14145876},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbadis.2014.10.015},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25445539},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25445539},
    doi = {10.1016/j.bbadis.2014.10.015},
    issn = {0006-3002},
    journal = {Biochimica et biophysica acta},
    month = jan,
    number = {1},
    pages = {83--91},
    pmid = {25445539},
    posted-at = {2016-09-24 18:07:36},
    priority = {2},
    title = {Zinc-induced structural changes of the disordered tppp/p25 inhibits its degradation by the proteasome.},
    url = {http://dx.doi.org/10.1016/j.bbadis.2014.10.015},
    volume = {1852},
    year = {2015}
    }

  • V. Deletioglu, E. Tuncay, A. Toy, M. Atalay, and B. Turan, “Immuno-spin trapping detection of antioxidant/pro-oxidant properties of zinc or selenium on DNA and protein radical formation via hydrogen peroxide.,” Molecular and cellular biochemistry, vol. 409, iss. 1-2, pp. 23-31, 2015. doi:10.1007/s11010-015-2508-x
    [Abstract]

    Trace elements can participate in the catalysis of group-transfer reactions and can serve as their structural components. However, most of them including zinc and selenium have multifunctional roles in biological environments such as antioxidant and/or pro-oxidant effects, as concentration-dependent manner. Although it has been demonstrated the antioxidant actions of either selenium or zinc compounds, there are several documents pointing out their pro-oxidant/oxidant roles in biological systems. Here we have used {ELISA}-based immuno-spin trapping, a method for detection of free radical formation, to detect whether or not a zinc compound, {Zn3(PO4})2, or a selenium compound, {Na2SeO3}, has antioxidant and/or pro-oxidant effect on {5,5-Dimethyl}-{1-Pyrroline}-{N-Oxide} ({DMPO})-{DNA} nitrone adducts induced with {Cu(II})-{H2O2}-oxidizing system in in vitro preparations. Second, we examined whether this technique is capable to demonstrate the different {DMPO}-protein nitrone adduct productions in isolated protein crude of hearts from normal rats ({CON}) or rats with metabolic syndrome ({MetS}). Our data demonstrated that either Zn(2+) (100 {µM}) or {SeO3}(-2) (50 {nM}) has very strong antioxidant action against 200 {µM} {H2O2}-induced {DMPO}-{DNA} nitrone adduct production, whereas their higher concentrations have apparent pro-oxidant actions. We also used verification by Western blotting analysis whether immuno-spin trapping can be used to assess {H2O2}-induced {DMPO}-protein nitrone adducts in heart protein crudes. Our Western blot data further confirmed the {ELISA}-data from proteins and demonstrated how Zn(2+) or {SeO3}(-2) are dual-functioning ions such as antioxidant at lower concentrations while pro-oxidant at higher concentrations. Particularly, our present data with {SeO3}(-2) in {DMPO}-protein nitrone adducts, being in line with our previous observation on its dual-actions in ischemia/reperfusion-induced damaged heart, have shown that this ion has higher pro-oxidant actions over 50 {nM} in {MetS}-group compared to that of {CON} group.

    @article{citeulike:14145874,
    abstract = {Trace elements can participate in the catalysis of group-transfer reactions and can serve as their structural components. However, most of them including zinc and selenium have multifunctional roles in biological environments such as antioxidant and/or pro-oxidant effects, as concentration-dependent manner. Although it has been demonstrated the antioxidant actions of either selenium or zinc compounds, there are several documents pointing out their pro-oxidant/oxidant roles in biological systems. Here we have used {ELISA}-based immuno-spin trapping, a method for detection of free radical formation, to detect whether or not a zinc compound, {Zn3(PO4})2, or a selenium compound, {Na2SeO3}, has antioxidant and/or pro-oxidant effect on {5,5-Dimethyl}-{1-Pyrroline}-{N-Oxide} ({DMPO})-{DNA} nitrone adducts induced with {Cu(II})-{H2O2}-oxidizing system in in vitro preparations. Second, we examined whether this technique is capable to demonstrate the different {DMPO}-protein nitrone adduct productions in isolated protein crude of hearts from normal rats ({CON}) or rats with metabolic syndrome ({MetS}). Our data demonstrated that either Zn(2+) (100 {µM}) or {SeO3}(-2) (50 {nM}) has very strong antioxidant action against 200 {µM} {H2O2}-induced {DMPO}-{DNA} nitrone adduct production, whereas their higher concentrations have apparent pro-oxidant actions. We also used verification by Western blotting analysis whether immuno-spin trapping can be used to assess {H2O2}-induced {DMPO}-protein nitrone adducts in heart protein crudes. Our Western blot data further confirmed the {ELISA}-data from proteins and demonstrated how Zn(2+) or {SeO3}(-2) are dual-functioning ions such as antioxidant at lower concentrations while pro-oxidant at higher concentrations. Particularly, our present data with {SeO3}(-2) in {DMPO}-protein nitrone adducts, being in line with our previous observation on its dual-actions in ischemia/reperfusion-induced damaged heart, have shown that this ion has higher pro-oxidant actions over 50 {nM} in {MetS}-group compared to that of {CON} group.},
    author = {Deletioglu, Vedia and Tuncay, Erkan and Toy, Aysegul and Atalay, Mustafa and Turan, Belma},
    citeulike-article-id = {14145874},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s11010-015-2508-x},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26169985},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26169985},
    doi = {10.1007/s11010-015-2508-x},
    issn = {1573-4919},
    journal = {Molecular and cellular biochemistry},
    month = nov,
    number = {1-2},
    pages = {23--31},
    pmid = {26169985},
    posted-at = {2016-09-24 18:04:16},
    priority = {2},
    title = {Immuno-spin trapping detection of antioxidant/pro-oxidant properties of zinc or selenium on {DNA} and protein radical formation via hydrogen peroxide.},
    url = {http://dx.doi.org/10.1007/s11010-015-2508-x},
    volume = {409},
    year = {2015}
    }

  • D. Gilad, S. Shorer, M. Ketzef, A. Friedman, I. Sekler, E. Aizenman, and M. Hershfinkel, “Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures.,” Neurobiology of disease, vol. 81, pp. 4-13, 2015. doi:10.1016/j.nbd.2014.12.020
    [Abstract]

    The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor {mZnR}/{GPR39} in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of {mZnR}/{GPR39} enhances inhibitory drive in the hippocampus by upregulating neuronal {K(+)/Cl}(-) co-transporter 2 ({KCC2}) activity. Here, we first show that {mZnR}/{GPR39} knockout ({KO}) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type ({WT}) littermates. Kainate also substantially enhances seizure-associated gamma oscillatory activity in juvenile {mZnR}/{GPR39} {KO} hippocampal slices, a phenomenon that can be reproduced in {WT} tissue by extracellular Zn(2+) chelation. Importantly, kainate-induced synaptic Zn(2+) release enhances surface expression and transport activity of {KCC2} in {WT}, but not {mZnR}/{GPR39} {KO} hippocampal neurons. Kainate-dependent upregulation of {KCC2} requires {mZnR}/{GPR39} activation of the Gαq/phospholipase C/extracellular regulated kinase ({ERK1}/2) signaling cascade. We suggest that {mZnR}/{GPR39}-dependent upregulation of {KCC2} activity provides homeostatic adaptation to an excitotoxic stimulus by increasing inhibition. As such, {mZnR}/{GPR39} may provide a novel pharmacological target for dampening epileptic seizure activity. Copyright {\copyright} 2014 Elsevier Inc. All rights reserved.

    @article{citeulike:14145871,
    abstract = {The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor {mZnR}/{GPR39} in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of {mZnR}/{GPR39} enhances inhibitory drive in the hippocampus by upregulating neuronal {K(+)/Cl}(-) co-transporter 2 ({KCC2}) activity. Here, we first show that {mZnR}/{GPR39} knockout ({KO}) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type ({WT}) littermates. Kainate also substantially enhances seizure-associated gamma oscillatory activity in juvenile {mZnR}/{GPR39} {KO} hippocampal slices, a phenomenon that can be reproduced in {WT} tissue by extracellular Zn(2+) chelation. Importantly, kainate-induced synaptic Zn(2+) release enhances surface expression and transport activity of {KCC2} in {WT}, but not {mZnR}/{GPR39} {KO} hippocampal neurons. Kainate-dependent upregulation of {KCC2} requires {mZnR}/{GPR39} activation of the Gαq/phospholipase C/extracellular regulated kinase ({ERK1}/2) signaling cascade. We suggest that {mZnR}/{GPR39}-dependent upregulation of {KCC2} activity provides homeostatic adaptation to an excitotoxic stimulus by increasing inhibition. As such, {mZnR}/{GPR39} may provide a novel pharmacological target for dampening epileptic seizure activity. Copyright {\copyright} 2014 Elsevier Inc. All rights reserved.},
    author = {Gilad, David and Shorer, Sharon and Ketzef, Maya and Friedman, Alon and Sekler, Israel and Aizenman, Elias and Hershfinkel, Michal},
    citeulike-article-id = {14145871},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.nbd.2014.12.020},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25562657},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25562657},
    doi = {10.1016/j.nbd.2014.12.020},
    issn = {1095-953X},
    journal = {Neurobiology of disease},
    month = sep,
    pages = {4--13},
    pmid = {25562657},
    posted-at = {2016-09-24 18:01:56},
    priority = {2},
    title = {Homeostatic regulation of {KCC2} activity by the zinc receptor {mZnR}/{GPR39} during seizures.},
    url = {http://dx.doi.org/10.1016/j.nbd.2014.12.020},
    volume = {81},
    year = {2015}
    }

  • M. Hershfinkel, D. Ford, S. Kelleher, and E. Aizenman, “Seashells by the zinc shore: a meeting report of the international society for zinc biology, asilomar, CA 2014.,” Metallomics : integrated biometal science, vol. 7, iss. 9, pp. 1299-1304, 2015. doi:10.1039/C5MT90029H
    @article{citeulike:14145866,
    author = {Hershfinkel, Michal and Ford, Dianne and Kelleher, Shannon and Aizenman, Elias},
    citeulike-article-id = {14145866},
    citeulike-linkout-0 = {http://dx.doi.org/10.1039/C5MT90029H},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26225429},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26225429},
    doi = {10.1039/C5MT90029H},
    issn = {1756-591X},
    journal = {Metallomics : integrated biometal science},
    month = sep,
    number = {9},
    pages = {1299--1304},
    pmid = {26225429},
    posted-at = {2016-09-24 17:46:07},
    priority = {2},
    title = {Seashells by the zinc shore: a meeting report of the International Society for Zinc Biology, Asilomar, {CA} 2014.},
    url = {http://dx.doi.org/10.1039/C5MT90029H},
    volume = {7},
    year = {2015}
    }

  • T. Ganay, H. Asraf, E. Aizenman, M. Bogdanovic, I. Sekler, and M. Hershfinkel, “Regulation of neuronal pH by the metabotropic zn(2+)-sensing gq-coupled receptor, mZnR/GPR39.,” Journal of neurochemistry, vol. 135, iss. 5, pp. 897-907, 2015. doi:10.1111/jnc.13367
    [Abstract]

    Synaptically released Zn(2+) acts as a neurotransmitter, in part, by activating the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor ({mZnR}/{GPR39}). In previous work using epithelial cells, we described crosstalk between Zn(2+) signaling and changes in intracellular {pH} and/or extracellular {pH} ({pHe}). As {pH} changes accompany neuronal activity under physiological and pathological conditions, we tested whether Zn(2+) signaling is involved in regulation of neuronal {pH}. Here, we report that up-regulation of a major H(+) extrusion pathway, the {Na(+)/H}(+) exchanger ({NHE}), is induced by {mZnR}/{GPR39} activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons in vitro. We also observed that changes in {pHe} can modulate neuronal {mZnR}/{GPR39}-dependent signaling, resulting in reduced activity at {pHe} 8 or 6.5. Similarly, Zn(2+)-dependent extracellular-regulated kinase 1/2 phosphorylation and up-regulation of {NHE} activity were absent at acidic {pHe}. Thus, our results suggest that when {pHe} is maintained within the physiological range, {mZnR}/{GPR39} activation can up-regulate {NHE}-dependent recovery from intracellular acidification. During acidosis, as {pHe} drops, {mZnR}/{GPR39}-dependent {NHE} activation is inhibited, thereby attenuating further H(+) extrusion. This mechanism may serve to protect neurons from excessive decreases in {pHe}. Thus, {mZnR}/{GPR39} signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular {pH} changes in the brain. We show that the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor ({mZnR}/{GPR39}) activation induces up-regulation of a major neuronal H(+) extrusion pathway, the {Na(+)/H}(+) exchanger ({NHE}), thereby enhancing neuronal recovery from intracellular acidification. Changes in extracellular {pH} ({pHe}), however, modulate neuronal {mZnR}/{GPR39}-dependent signaling, resulting in reduced activity at {pHe} 8 or 6.5. This mechanism may serve to protect neurons from excessive decreases in {pHe} during acidosis. Hence, {mZnR}/{GPR39} signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular {pH} changes in the brain. {\copyright} 2015 International Society for Neurochemistry.

    @article{citeulike:14145864,
    abstract = {Synaptically released Zn(2+) acts as a neurotransmitter, in part, by activating the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor ({mZnR}/{GPR39}). In previous work using epithelial cells, we described crosstalk between Zn(2+) signaling and changes in intracellular {pH} and/or extracellular {pH} ({pHe}). As {pH} changes accompany neuronal activity under physiological and pathological conditions, we tested whether Zn(2+) signaling is involved in regulation of neuronal {pH}. Here, we report that up-regulation of a major H(+) extrusion pathway, the {Na(+)/H}(+) exchanger ({NHE}), is induced by {mZnR}/{GPR39} activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons in vitro. We also observed that changes in {pHe} can modulate neuronal {mZnR}/{GPR39}-dependent signaling, resulting in reduced activity at {pHe} 8 or 6.5. Similarly, Zn(2+)-dependent extracellular-regulated kinase 1/2 phosphorylation and up-regulation of {NHE} activity were absent at acidic {pHe}. Thus, our results suggest that when {pHe} is maintained within the physiological range, {mZnR}/{GPR39} activation can up-regulate {NHE}-dependent recovery from intracellular acidification. During acidosis, as {pHe} drops, {mZnR}/{GPR39}-dependent {NHE} activation is inhibited, thereby attenuating further H(+) extrusion. This mechanism may serve to protect neurons from excessive decreases in {pHe}. Thus, {mZnR}/{GPR39} signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular {pH} changes in the brain. We show that the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor ({mZnR}/{GPR39}) activation induces up-regulation of a major neuronal H(+) extrusion pathway, the {Na(+)/H}(+) exchanger ({NHE}), thereby enhancing neuronal recovery from intracellular acidification. Changes in extracellular {pH} ({pHe}), however, modulate neuronal {mZnR}/{GPR39}-dependent signaling, resulting in reduced activity at {pHe} 8 or 6.5. This mechanism may serve to protect neurons from excessive decreases in {pHe} during acidosis. Hence, {mZnR}/{GPR39} signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular {pH} changes in the brain. {\copyright} 2015 International Society for Neurochemistry.},
    author = {Ganay, Thibault and Asraf, Hila and Aizenman, Elias and Bogdanovic, Milos and Sekler, Israel and Hershfinkel, Michal},
    citeulike-article-id = {14145864},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/jnc.13367},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26375174},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26375174},
    doi = {10.1111/jnc.13367},
    issn = {1471-4159},
    journal = {Journal of neurochemistry},
    month = dec,
    number = {5},
    pages = {897--907},
    pmid = {26375174},
    posted-at = {2016-09-24 17:45:06},
    priority = {2},
    title = {Regulation of neuronal {pH} by the metabotropic Zn(2+)-sensing Gq-coupled receptor, {mZnR}/{GPR39}.},
    url = {http://dx.doi.org/10.1111/jnc.13367},
    volume = {135},
    year = {2015}
    }

  • A. M. Hessels, P. Chabosseau, M. H. Bakker, W. Engelen, G. A. Rutter, K. M. Taylor, and M. Merkx, “eZinCh-2: a versatile, genetically encoded FRET sensor for cytosolic and intraorganelle zn(2+) imaging.,” Acs chemical biology, vol. 10, iss. 9, pp. 2126-2134, 2015. doi:10.1021/acschembio.5b00211
    [Abstract]

    Zn(2+) plays essential and diverse roles in numerous cellular processes. To get a better understanding of intracellular Zn(2+) homeostasis and the putative signaling role of Zn(2+), various fluorescent sensors have been developed that allow monitoring of Zn(2+) concentrations in single living cells in real time. Thus far, two families of genetically encoded {FRET}-based Zn(2+) sensors have been most widely applied, the {eCALWY} sensors developed by our group and the {ZapCY} sensors developed by Palmer and co-workers. Both have been successfully used to measure cytosolic free Zn(2+), but distinctly different concentrations have been reported when using these sensors to measure Zn(2+) concentrations in the {ER} and mitochondria. Here, we report the development of a versatile alternative {FRET} sensor containing a de novo {Cys2His2} binding pocket that was created on the surface of the donor and acceptor fluorescent domains. This {eZinCh}-2 sensor binds Zn(2+) with a high affinity that is similar to that of {eCALWY}-4 (Kd = 1 {nM} at {pH} 7.1), while displaying a substantially larger change in emission ratio. {eZinCh}-2 not only provides an attractive alternative for measuring Zn(2+) in the cytosol but was also successfully used for measuring Zn(2+) in the {ER}, mitochondria, and secretory vesicles. Moreover, organelle-targeted {eZinCh}-2 can also be used in combination with the previously reported {redCALWY} sensors to allow multicolor imaging of intracellular Zn(2+) simultaneously in the cytosol and the {ER} or mitochondria.

    @article{citeulike:14145863,
    abstract = {Zn(2+) plays essential and diverse roles in numerous cellular processes. To get a better understanding of intracellular Zn(2+) homeostasis and the putative signaling role of Zn(2+), various fluorescent sensors have been developed that allow monitoring of Zn(2+) concentrations in single living cells in real time. Thus far, two families of genetically encoded {FRET}-based Zn(2+) sensors have been most widely applied, the {eCALWY} sensors developed by our group and the {ZapCY} sensors developed by Palmer and co-workers. Both have been successfully used to measure cytosolic free Zn(2+), but distinctly different concentrations have been reported when using these sensors to measure Zn(2+) concentrations in the {ER} and mitochondria. Here, we report the development of a versatile alternative {FRET} sensor containing a de novo {Cys2His2} binding pocket that was created on the surface of the donor and acceptor fluorescent domains. This {eZinCh}-2 sensor binds Zn(2+) with a high affinity that is similar to that of {eCALWY}-4 (Kd = 1 {nM} at {pH} 7.1), while displaying a substantially larger change in emission ratio. {eZinCh}-2 not only provides an attractive alternative for measuring Zn(2+) in the cytosol but was also successfully used for measuring Zn(2+) in the {ER}, mitochondria, and secretory vesicles. Moreover, organelle-targeted {eZinCh}-2 can also be used in combination with the previously reported {redCALWY} sensors to allow multicolor imaging of intracellular Zn(2+) simultaneously in the cytosol and the {ER} or mitochondria.},
    author = {Hessels, Anne M. and Chabosseau, Pauline and Bakker, Maarten H. and Engelen, Wouter and Rutter, Guy A. and Taylor, Kathryn M. and Merkx, Maarten},
    citeulike-article-id = {14145863},
    citeulike-linkout-0 = {http://dx.doi.org/10.1021/acschembio.5b00211},
    citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/acschembio.5b00211},
    citeulike-linkout-2 = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577962/},
    citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/26151333},
    citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=26151333},
    day = {18},
    doi = {10.1021/acschembio.5b00211},
    issn = {1554-8937},
    journal = {ACS chemical biology},
    month = sep,
    number = {9},
    pages = {2126--2134},
    pmcid = {PMC4577962},
    pmid = {26151333},
    posted-at = {2016-09-24 17:44:49},
    priority = {2},
    title = {{eZinCh}-2: A Versatile, Genetically Encoded {FRET} Sensor for Cytosolic and Intraorganelle Zn(2+) Imaging.},
    url = {http://dx.doi.org/10.1021/acschembio.5b00211},
    volume = {10},
    year = {2015}
    }

  • C. Cai, P. Lin, H. Zhu, J. K. Ko, M. Hwang, T. Tan, Z. Pan, I. Korichneva, and J. Ma, “Zinc binding to MG53 protein facilitates repair of injury to cell membranes.,” The journal of biological chemistry, vol. 290, iss. 22, pp. 13830-13839, 2015. doi:10.1074/jbc.M114.620690
    [Abstract]

    Zinc is an essential trace element that participates in a wide range of biological functions, including wound healing. Although Zn(2+) deficiency has been linked to compromised wound healing and tissue repair in human diseases, the molecular mechanisms underlying Zn(2+)-mediated tissue repair remain unknown. Our previous studies established that {MG53}, a {TRIM} (tripartite motif) family protein, is an essential component of the cell membrane repair machinery. Domain homology analysis revealed that {MG53} contains two Zn(2+)-binding motifs. Here, we show that Zn(2+) binding to {MG53} is indispensable to assembly of the cell membrane repair machinery. Live cell imaging illustrated that Zn(2+) entry from extracellular space is essential for translocation of {MG53}-containing vesicles to the acute membrane injury sites for formation of a repair patch. The effect of Zn(2+) on membrane repair is abolished in mg53(-/-) muscle fibers, suggesting that {MG53} functions as a potential target for Zn(2+) during membrane repair. Mutagenesis studies suggested that both {RING} and B-box motifs of {MG53} constitute Zn(2+)-binding domains that contribute to {MG53}-mediated membrane repair. Overall, this study establishes a base for Zn(2+) interaction with {MG53} in protection against injury to the cell membrane. {\copyright} 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

    @article{citeulike:14145856,
    abstract = {Zinc is an essential trace element that participates in a wide range of biological functions, including wound healing. Although Zn(2+) deficiency has been linked to compromised wound healing and tissue repair in human diseases, the molecular mechanisms underlying Zn(2+)-mediated tissue repair remain unknown. Our previous studies established that {MG53}, a {TRIM} (tripartite motif) family protein, is an essential component of the cell membrane repair machinery. Domain homology analysis revealed that {MG53} contains two Zn(2+)-binding motifs. Here, we show that Zn(2+) binding to {MG53} is indispensable to assembly of the cell membrane repair machinery. Live cell imaging illustrated that Zn(2+) entry from extracellular space is essential for translocation of {MG53}-containing vesicles to the acute membrane injury sites for formation of a repair patch. The effect of Zn(2+) on membrane repair is abolished in mg53(-/-) muscle fibers, suggesting that {MG53} functions as a potential target for Zn(2+) during membrane repair. Mutagenesis studies suggested that both {RING} and B-box motifs of {MG53} constitute Zn(2+)-binding domains that contribute to {MG53}-mediated membrane repair. Overall, this study establishes a base for Zn(2+) interaction with {MG53} in protection against injury to the cell membrane. {\copyright} 2015 by The American Society for Biochemistry and Molecular Biology, Inc.},
    author = {Cai, Chuanxi and Lin, Peihui and Zhu, Hua and Ko, Jae-Kyun K. and Hwang, Moonsun and Tan, Tao and Pan, Zui and Korichneva, Irina and Ma, Jianjie},
    citeulike-article-id = {14145856},
    citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M114.620690},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25869134},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25869134},
    day = {29},
    doi = {10.1074/jbc.M114.620690},
    issn = {1083-351X},
    journal = {The Journal of biological chemistry},
    month = may,
    number = {22},
    pages = {13830--13839},
    pmid = {25869134},
    posted-at = {2016-09-24 17:42:06},
    priority = {2},
    title = {Zinc Binding to {MG53} Protein Facilitates Repair of Injury to Cell Membranes.},
    url = {http://dx.doi.org/10.1074/jbc.M114.620690},
    volume = {290},
    year = {2015}
    }

  • R. Chhabra, B. Ruozi, A. Vilella, D. Belletti, K. Mangus, S. Pfaender, T. Sarowar, T. M. M. Boeckers, M. Zoli, F. Forni, M. A. A. Vandelli, G. Tosi, and A. M. M. Grabrucker, “Application of polymeric nanoparticles for CNS targeted zinc delivery in vivo.,” Cns & neurological disorders drug targets, vol. 14, iss. 8, pp. 1041-1053, 2015. doi:10.2174/1871527314666150821111455
    [Abstract]

    A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson’s and Alzheimer’s disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non – invasive method to selectively enrich zinc in the brain within a small amount of time.

    @article{citeulike:14145853,
    abstract = {A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non - invasive method to selectively enrich zinc in the brain within a small amount of time.},
    author = {Chhabra, Resham and Ruozi, Barbara and Vilella, Antonietta and Belletti, Daniela and Mangus, Katharina and Pfaender, Stefanie and Sarowar, Tasnuva and Boeckers, Tobias Maria M. and Zoli, Michele and Forni, Flavio and Vandelli, Maria Angela A. and Tosi, Giovanni and Grabrucker, Andreas Martin M.},
    citeulike-article-id = {14145853},
    citeulike-linkout-0 = {http://dx.doi.org/10.2174/1871527314666150821111455},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26295815},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26295815},
    doi = {10.2174/1871527314666150821111455},
    issn = {1996-3181},
    journal = {CNS \& neurological disorders drug targets},
    number = {8},
    pages = {1041--1053},
    pmid = {26295815},
    posted-at = {2016-09-24 17:40:47},
    priority = {2},
    title = {Application of Polymeric Nanoparticles for {CNS} Targeted Zinc Delivery In Vivo.},
    url = {http://dx.doi.org/10.2174/1871527314666150821111455},
    volume = {14},
    year = {2015}
    }

  • T. E. Douglas, M. Pilarz, M. Lopez-Heredia, G. Brackman, D. Schaubroeck, L. Balcaen, V. Bliznuk, P. Dubruel, C. Knabe-Ducheyne, F. Vanhaecke, T. Coenye, and E. Pamula, “Composites of gellan gum hydrogel enzymatically mineralized with calcium-zinc phosphate for bone regeneration with antibacterial activity.,” Journal of tissue engineering and regenerative medicine, 2015. doi:10.1002/term.2062
    [Abstract]

    Gellan gum hydrogels functionalized with alkaline phosphatase were enzymatically mineralized with phosphates in mineralization medium containing calcium (Ca) and zinc (Zn) to improve their suitability as biomaterials for bone regeneration. The aims of the study were to endow mineralized hydrogels with antibacterial activity by incorporation of Zn in the inorganic phase, and to investigate the effect of Zn incorporation on the amount and type of mineral formed, the compressive modulus of the mineralized hydrogels and on their ability to support adhesion and growth of {MC3T3}-E1 osteoblast-like cells. Mineralization medium contained glycerophosphate (0.05 m) and three different molar {Ca:Zn} ratios, 0.05:0, 0.04:0.01 and 0.025:0.025 (all mol/dm(3) ), hereafter referred to as A, B and C, respectively. {FTIR}, {SAED} and {TEM} analysis revealed that incubation for 14 days caused the formation of predominantly amorphous mineral phases in sample groups A, B and C. The presence of Zn in sample groups B and C was associated with a drop in the amount of mineral formed and a smaller mineral deposit morphology, as observed by {SEM}. {ICP}-{OES} revealed that Zn was preferentially incorporated into mineral compared to Ca. Mechanical testing revealed a decrease in compressive modulus in sample group C. Sample groups B and C, but not A, showed antibacterial activity against biofilm-forming, methicillin-resistant Staphylococcus aureus. All sample groups supported cell growth. Zn incorporation increased the viable cell number. The highest values were seen on sample group C. In conclusion, the sample group containing the most Zn, i.e. group C, appears to be the most promising. Copyright {\copyright} 2015 John Wiley & Sons, Ltd. Copyright {\copyright} 2015 John Wiley & Sons, Ltd.

    @article{citeulike:14145851,
    abstract = {Gellan gum hydrogels functionalized with alkaline phosphatase were enzymatically mineralized with phosphates in mineralization medium containing calcium (Ca) and zinc (Zn) to improve their suitability as biomaterials for bone regeneration. The aims of the study were to endow mineralized hydrogels with antibacterial activity by incorporation of Zn in the inorganic phase, and to investigate the effect of Zn incorporation on the amount and type of mineral formed, the compressive modulus of the mineralized hydrogels and on their ability to support adhesion and growth of {MC3T3}-E1 osteoblast-like cells. Mineralization medium contained glycerophosphate (0.05 m) and three different molar {Ca:Zn} ratios, 0.05:0, 0.04:0.01 and 0.025:0.025 (all mol/dm(3) ), hereafter referred to as A, B and C, respectively. {FTIR}, {SAED} and {TEM} analysis revealed that incubation for 14 days caused the formation of predominantly amorphous mineral phases in sample groups A, B and C. The presence of Zn in sample groups B and C was associated with a drop in the amount of mineral formed and a smaller mineral deposit morphology, as observed by {SEM}. {ICP}-{OES} revealed that Zn was preferentially incorporated into mineral compared to Ca. Mechanical testing revealed a decrease in compressive modulus in sample group C. Sample groups B and C, but not A, showed antibacterial activity against biofilm-forming, methicillin-resistant Staphylococcus aureus. All sample groups supported cell growth. Zn incorporation increased the viable cell number. The highest values were seen on sample group C. In conclusion, the sample group containing the most Zn, i.e. group C, appears to be the most promising. Copyright {\copyright} 2015 John Wiley \& Sons, Ltd. Copyright {\copyright} 2015 John Wiley \& Sons, Ltd.},
    author = {Douglas, Timothy E. and Pilarz, Magdalena and Lopez-Heredia, Marco and Brackman, Gilles and Schaubroeck, David and Balcaen, Lieve and Bliznuk, Vitaliy and Dubruel, Peter and Knabe-Ducheyne, Christine and Vanhaecke, Frank and Coenye, Tom and Pamula, Elzbieta},
    citeulike-article-id = {14145851},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/term.2062},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26174042},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26174042},
    day = {15},
    doi = {10.1002/term.2062},
    issn = {1932-7005},
    journal = {Journal of tissue engineering and regenerative medicine},
    month = jul,
    pmid = {26174042},
    posted-at = {2016-09-24 17:39:50},
    priority = {2},
    title = {Composites of gellan gum hydrogel enzymatically mineralized with calcium-zinc phosphate for bone regeneration with antibacterial activity.},
    url = {http://dx.doi.org/10.1002/term.2062},
    year = {2015}
    }

  • S. B. Nygaard, N. S. Lund, A. Larsen, N. Pedersen, J. Rungby, and K. Smidt, “Exogenous metallothionein potentiates the insulin response at normal glucose concentrations in INS-1E beta-cells without disturbing intracellular ZnT8 expression.,” Basic & clinical pharmacology & toxicology, vol. 116, iss. 2, pp. 173-177, 2015. doi:10.1111/bcpt.12287
    @article{citeulike:14145849,
    author = {Nygaard, Sanne B. and Lund, Ninna S. and Larsen, Agnete and Pedersen, Nanna and Rungby, J{\o}rgen and Smidt, Kamille},
    citeulike-article-id = {14145849},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/bcpt.12287},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/24964825},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=24964825},
    doi = {10.1111/bcpt.12287},
    issn = {1742-7843},
    journal = {Basic \& clinical pharmacology \& toxicology},
    month = feb,
    number = {2},
    pages = {173--177},
    pmid = {24964825},
    posted-at = {2016-09-24 17:38:14},
    priority = {2},
    title = {Exogenous metallothionein potentiates the insulin response at normal glucose concentrations in {INS}-{1E} beta-cells without disturbing intracellular {ZnT8} expression.},
    url = {http://dx.doi.org/10.1111/bcpt.12287},
    volume = {116},
    year = {2015}
    }

  • T. Maxel, K. Smidt, A. Larsen, M. Bennetzen, K. Cullberg, K. Fjeldborg, S. Lund, S. B. Pedersen, and J. Rungby, “Gene expression of the zinc transporter ZIP14 (SLC39a14) is affected by weight loss and metabolic status and associates with PPARγ in human adipose tissue and 3T3-l1 pre-adipocytes.,” Bmc obesity, vol. 2, 2015. doi:10.1186/s40608-015-0076-y
    [Abstract]

    The expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc dyshomeostasis is common in obese individuals. In the liver, zinc influx transporter {ZIP14}, affects proliferation and glucose metabolism but the role of {ZIP14} in adipose tissue is still unknown. This study investigates {ZIP14} gene expression in human adipose tissue before and after weight loss as well as the regulation of {ZIP14} during early adipogenesis. Fourteen obese individuals were investigated before and after a 10 week weight loss intervention and compared to 14 non-obese controls. Gene expressions of {ZIP14} and peroxisome proliferator-activated receptor γ ({PPARγ}) were measured in subcutaneous adipose tissue and correlated with metabolic and inflammatory markers. Further, we investigated gene expression of {ZIP14} and {PPARγ} during early adipogenesis of {3T3}-L1 pre-adipocytes, together with an in silico analysis of {PPARγ} binding motifs in the promoter sequence of {ZIP14}. {ZIP14} was down-regulated in obese individuals compared to non-obese controls (p = 0.0007) and was up-regulated after weight loss (p = 0.0005). Several metabolic markers of clinical importance, including body mass index, triglyceride, and insulin resistance, were inversely correlated with {ZIP14}. During early adipogensis an up-regulation of {ZIP14} gene expression was found. {PPARγ} gene expression was positively correlated with the {ZIP14} gene expression in both adipose tissue and during adipogenesis. However, in silico analysis revealed that the {ZIP14} promoter does not contain {PPARγ}-binding motifs. We hypothesize that {ZIP14}-mediated zinc influx might directly influence {PPARγ} activity and that {ZIP14} may regulate expansion and function of adipose tissue and serve as a potential biomarker for metabolic stress.

    @article{citeulike:14145848,
    abstract = {The expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc dyshomeostasis is common in obese individuals. In the liver, zinc influx transporter {ZIP14}, affects proliferation and glucose metabolism but the role of {ZIP14} in adipose tissue is still unknown. This study investigates {ZIP14} gene expression in human adipose tissue before and after weight loss as well as the regulation of {ZIP14} during early adipogenesis. Fourteen obese individuals were investigated before and after a 10 week weight loss intervention and compared to 14 non-obese controls. Gene expressions of {ZIP14} and peroxisome proliferator-activated receptor γ ({PPARγ}) were measured in subcutaneous adipose tissue and correlated with metabolic and inflammatory markers. Further, we investigated gene expression of {ZIP14} and {PPARγ} during early adipogenesis of {3T3}-L1 pre-adipocytes, together with an in silico analysis of {PPARγ} binding motifs in the promoter sequence of {ZIP14}. {ZIP14} was down-regulated in obese individuals compared to non-obese controls (p = 0.0007) and was up-regulated after weight loss (p = 0.0005). Several metabolic markers of clinical importance, including body mass index, triglyceride, and insulin resistance, were inversely correlated with {ZIP14}. During early adipogensis an up-regulation of {ZIP14} gene expression was found. {PPARγ} gene expression was positively correlated with the {ZIP14} gene expression in both adipose tissue and during adipogenesis. However, in silico analysis revealed that the {ZIP14} promoter does not contain {PPARγ}-binding motifs. We hypothesize that {ZIP14}-mediated zinc influx might directly influence {PPARγ} activity and that {ZIP14} may regulate expansion and function of adipose tissue and serve as a potential biomarker for metabolic stress.},
    author = {Maxel, Trine and Smidt, Kamille and Larsen, Agnete and Bennetzen, Marianne and Cullberg, Karina and Fjeldborg, Karen and Lund, Sten and Pedersen, Steen B. and Rungby, J{\o}rgen},
    citeulike-article-id = {14145848},
    citeulike-linkout-0 = {http://dx.doi.org/10.1186/s40608-015-0076-y},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26623077},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26623077},
    doi = {10.1186/s40608-015-0076-y},
    issn = {2052-9538},
    journal = {BMC obesity},
    pmid = {26623077},
    posted-at = {2016-09-24 17:37:38},
    priority = {2},
    title = {Gene expression of the zinc transporter {ZIP14} ({SLC39a14}) is affected by weight loss and metabolic status and associates with {PPARγ} in human adipose tissue and {3T3}-L1 pre-adipocytes.},
    url = {http://dx.doi.org/10.1186/s40608-015-0076-y},
    volume = {2},
    year = {2015}
    }

  • S. S. Leal, J. S. Cristóvão, A. Biesemeier, I. Cardoso, and C. M. Gomes, “Aberrant zinc binding to immature conformers of metal-free copper-zinc superoxide dismutase triggers amorphous aggregation.,” Metallomics : integrated biometal science, vol. 7, iss. 2, pp. 333-346, 2015. doi:10.1039/C4MT00278D
    [Abstract]

    Superoxide dismutase 1 ({SOD1}) is a {Cu/Zn} metalloenzyme that aggregates in amyotrophic lateral sclerosis ({ALS}), a fatal neurodegenerative disorder. Correct metal insertion during {SOD1} biosynthesis is critical to prevent misfolding; however Zn(2+) can bind to the copper-site leading to an aberrantly metallated protein. These effects of Zn(2+) misligation on {SOD1} aggregation remain to be explored, even though Zn(2+) levels are upregulated in {ALS} motor neurons. Here we use complementary biophysical methods to investigate Zn(2+) binding and its effects on the aggregation of three immature metal-free {SOD1} conformers that represent biogenesis intermediates: dimeric, monomeric and reduced monomeric {SOD1}. Using isothermal titration calorimetry we determined that Zn(2+) binds to all conformers both at the zinc- as well as to the copper-site; however Zn(2+) binding mechanisms to the zinc-site have distinct characteristics across immature conformers. We show that this ‘zinc overload’ of immature {SOD1} promotes intermolecular interactions, as evidenced by dynamic light scattering and {ThT} fluorescence kinetic studies. Analysis of aged zinc-induced aggregates by energy-dispersive X-ray and electron energy-loss spectroscopy shows that aggregates integrate some Zn(2+). In addition, electron diffraction analysis identifies nano-scaled crystalline materials and amyloid fibril-like reflections. Transmission electron microscopy reveals that Zn(2+) diverts the {SOD1} aggregation pathway from fibrils to amorphous aggregate, and electrophoretic analysis evidences an increase in insoluble materials. Overall, we provide evidence that aberrant zinc coordination to immature conformers broadens the population of {SOD1} misfolded species at early aggregation stages and provide evidence for a high structural polymorphism and heterogeneity of {SOD1} aggregates.

    @article{citeulike:14145846,
    abstract = {Superoxide dismutase 1 ({SOD1}) is a {Cu/Zn} metalloenzyme that aggregates in amyotrophic lateral sclerosis ({ALS}), a fatal neurodegenerative disorder. Correct metal insertion during {SOD1} biosynthesis is critical to prevent misfolding; however Zn(2+) can bind to the copper-site leading to an aberrantly metallated protein. These effects of Zn(2+) misligation on {SOD1} aggregation remain to be explored, even though Zn(2+) levels are upregulated in {ALS} motor neurons. Here we use complementary biophysical methods to investigate Zn(2+) binding and its effects on the aggregation of three immature metal-free {SOD1} conformers that represent biogenesis intermediates: dimeric, monomeric and reduced monomeric {SOD1}. Using isothermal titration calorimetry we determined that Zn(2+) binds to all conformers both at the zinc- as well as to the copper-site; however Zn(2+) binding mechanisms to the zinc-site have distinct characteristics across immature conformers. We show that this 'zinc overload' of immature {SOD1} promotes intermolecular interactions, as evidenced by dynamic light scattering and {ThT} fluorescence kinetic studies. Analysis of aged zinc-induced aggregates by energy-dispersive X-ray and electron energy-loss spectroscopy shows that aggregates integrate some Zn(2+). In addition, electron diffraction analysis identifies nano-scaled crystalline materials and amyloid fibril-like reflections. Transmission electron microscopy reveals that Zn(2+) diverts the {SOD1} aggregation pathway from fibrils to amorphous aggregate, and electrophoretic analysis evidences an increase in insoluble materials. Overall, we provide evidence that aberrant zinc coordination to immature conformers broadens the population of {SOD1} misfolded species at early aggregation stages and provide evidence for a high structural polymorphism and heterogeneity of {SOD1} aggregates.},
    author = {Leal, S\'{o}nia S. and Crist\'{o}v\~{a}o, Joana S. and Biesemeier, Antje and Cardoso, Isabel and Gomes, Cl\'{a}udio M.},
    citeulike-article-id = {14145846},
    citeulike-linkout-0 = {http://dx.doi.org/10.1039/C4MT00278D},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25554447},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25554447},
    doi = {10.1039/C4MT00278D},
    issn = {1756-591X},
    journal = {Metallomics : integrated biometal science},
    month = feb,
    number = {2},
    pages = {333--346},
    pmid = {25554447},
    posted-at = {2016-09-24 17:36:16},
    priority = {2},
    title = {Aberrant zinc binding to immature conformers of metal-free copper-zinc superoxide dismutase triggers amorphous aggregation.},
    url = {http://dx.doi.org/10.1039/C4MT00278D},
    volume = {7},
    year = {2015}
    }

  • T. Kochańczyk, A. Drozd, and A. Krężel, “Relationship between the architecture of zinc coordination and zinc binding affinity in proteins–insights into zinc regulation.,” Metallomics : integrated biometal science, vol. 7, iss. 2, pp. 244-257, 2015. doi:10.1039/C4MT00094C
    [Abstract]

    Zinc proteins are an integral component of the proteome of all domains of life. {Zn(II}), one of the most widespread transition elements, serves multiple functions in proteins, such as a catalytic co-factor, a structural center and a signaling component. The mechanism by which proteins associate with and dissociate from {Zn(II}) and the factors that modulate their affinity and stability remain incompletely understood. In this article, we aim to address how zinc binding sites present in proteins differ in their architecture and how their structural arrangement is associated with protein function, thermodynamic and kinetic stability, reactivity, as well as zinc-dependent regulation. Here, we emphasize that the concentration-dependent functionality of the interprotein zinc binding site may serve as another factor regulating the relationship between cellular {Zn(II}) availability and protein function.

    @article{citeulike:14145844,
    abstract = {Zinc proteins are an integral component of the proteome of all domains of life. {Zn(II}), one of the most widespread transition elements, serves multiple functions in proteins, such as a catalytic co-factor, a structural center and a signaling component. The mechanism by which proteins associate with and dissociate from {Zn(II}) and the factors that modulate their affinity and stability remain incompletely understood. In this article, we aim to address how zinc binding sites present in proteins differ in their architecture and how their structural arrangement is associated with protein function, thermodynamic and kinetic stability, reactivity, as well as zinc-dependent regulation. Here, we emphasize that the concentration-dependent functionality of the interprotein zinc binding site may serve as another factor regulating the relationship between cellular {Zn(II}) availability and protein function.},
    author = {Kocha\'{n}czyk, Tomasz and Drozd, Agnieszka and Krę\.{z}el, Artur},
    citeulike-article-id = {14145844},
    citeulike-linkout-0 = {http://dx.doi.org/10.1039/C4MT00094C},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25255078},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25255078},
    doi = {10.1039/C4MT00094C},
    issn = {1756-591X},
    journal = {Metallomics : integrated biometal science},
    month = feb,
    number = {2},
    pages = {244--257},
    pmid = {25255078},
    posted-at = {2016-09-24 17:35:15},
    priority = {2},
    title = {Relationship between the architecture of zinc coordination and zinc binding affinity in proteins--insights into zinc regulation.},
    url = {http://dx.doi.org/10.1039/C4MT00094C},
    volume = {7},
    year = {2015}
    }

  • J. Adamczyk, W. Bal, and A. Krężel, “Coordination properties of dithiobutylamine (DTBA), a newly introduced protein disulfide reducing agent.,” Inorganic chemistry, vol. 54, iss. 2, pp. 596-606, 2015. doi:10.1021/ic5025026
    [Abstract]

    The acid-base properties and metal-binding abilities of ({2S})-2-amino-1,4-dimercaptobutane, otherwise termed dithiobutylamine ({DTBA}), which is a newly introduced reagent useful for reducing protein and peptide disulfides, were studied in solution using potentiometry, ({1)H} {NMR} spectroscopy, spectropolarimetry, and {UV}-vis spectroscopy. The list of metal ions studied here includes {Zn(II}), {Cd(II}), {Ni(II}), {Co(II}), and {Cu(I}). We found that {DTBA} forms specific and very stable polynuclear and mononuclear complexes with all of these metal ions using both of its sulfur donors. {DTBA} forms complexes more stable than those of the commonly used disulfide reducing agent {DTT}, giving it more interference capacity in studies of metal binding in thiol-containing biomolecules. The ability of {DTBA} to strongly bind metal ions is reflected in its limited properties as a thiol protectant in their presence, which is manifested through slower disulfide reduction kinetics. We found that this effect correlated with the stabilities of the complexes. Additionally, the reducing properties of {DTBA} toward {MMTS}-modified papain ({MMTS} = S-methylmethanethiosulfonate) were also significantly affected by the investigated metal ions. In this case, however, electrostatic interactions and stereospecific effects, rather than metal-binding abilities, were found to be responsible for the reduced protective properties of {DTBA}. Despite its limitations, a high affinity toward metal ions makes {DTBA} an attractive agent in competition studies with metalloproteins.

    @article{citeulike:14145588,
    abstract = {The acid-base properties and metal-binding abilities of ({2S})-2-amino-1,4-dimercaptobutane, otherwise termed dithiobutylamine ({DTBA}), which is a newly introduced reagent useful for reducing protein and peptide disulfides, were studied in solution using potentiometry, ({1)H} {NMR} spectroscopy, spectropolarimetry, and {UV}-vis spectroscopy. The list of metal ions studied here includes {Zn(II}), {Cd(II}), {Ni(II}), {Co(II}), and {Cu(I}). We found that {DTBA} forms specific and very stable polynuclear and mononuclear complexes with all of these metal ions using both of its sulfur donors. {DTBA} forms complexes more stable than those of the commonly used disulfide reducing agent {DTT}, giving it more interference capacity in studies of metal binding in thiol-containing biomolecules. The ability of {DTBA} to strongly bind metal ions is reflected in its limited properties as a thiol protectant in their presence, which is manifested through slower disulfide reduction kinetics. We found that this effect correlated with the stabilities of the complexes. Additionally, the reducing properties of {DTBA} toward {MMTS}-modified papain ({MMTS} = S-methylmethanethiosulfonate) were also significantly affected by the investigated metal ions. In this case, however, electrostatic interactions and stereospecific effects, rather than metal-binding abilities, were found to be responsible for the reduced protective properties of {DTBA}. Despite its limitations, a high affinity toward metal ions makes {DTBA} an attractive agent in competition studies with metalloproteins.},
    author = {Adamczyk, Justyna and Bal, Wojciech and Krę\.{z}el, Artur},
    citeulike-article-id = {14145588},
    citeulike-linkout-0 = {http://dx.doi.org/10.1021/ic5025026},
    citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ic5025026},
    citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/25531180},
    citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=25531180},
    day = {20},
    doi = {10.1021/ic5025026},
    issn = {1520-510X},
    journal = {Inorganic chemistry},
    month = jan,
    number = {2},
    pages = {596--606},
    pmid = {25531180},
    posted-at = {2016-09-24 17:34:09},
    priority = {2},
    title = {Coordination properties of dithiobutylamine ({DTBA}), a newly introduced protein disulfide reducing agent.},
    url = {http://dx.doi.org/10.1021/ic5025026},
    volume = {54},
    year = {2015}
    }

  • M. Hohl, T. Kochańczyk, C. Tous, A. Aguilera, A. Krężel, and J. H. Petrini, “Interdependence of the rad50 hook and globular domain functions.,” Molecular cell, vol. 57, iss. 3, pp. 479-491, 2015. doi:10.1016/j.molcel.2014.12.018
    [Abstract]

    Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 ({ATM}) activation, nonhomologous end joining, and {DNA} double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular {ATPase} domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright {\copyright} 2015 Elsevier Inc. All rights reserved.

    @article{citeulike:14145586,
    abstract = {Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 ({ATM}) activation, nonhomologous end joining, and {DNA} double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular {ATPase} domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright {\copyright} 2015 Elsevier Inc. All rights reserved.},
    author = {Hohl, Marcel and Kocha\'{n}czyk, Tomasz and Tous, Cristina and Aguilera, Andr\'{e}s and Krę\.{z}el, Artur and Petrini, John H.},
    citeulike-article-id = {14145586},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.molcel.2014.12.018},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/25601756},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=25601756},
    day = {5},
    doi = {10.1016/j.molcel.2014.12.018},
    issn = {1097-4164},
    journal = {Molecular cell},
    month = feb,
    number = {3},
    pages = {479--491},
    pmid = {25601756},
    posted-at = {2016-09-24 17:33:44},
    priority = {2},
    title = {Interdependence of the rad50 hook and globular domain functions.},
    url = {http://dx.doi.org/10.1016/j.molcel.2014.12.018},
    volume = {57},
    year = {2015}
    }

  • A. Kocy{l}a, A. Pomorski, and A. Krężel, “Molar absorption coefficients and stability constants of metal complexes of 4-(2-pyridylazo)resorcinol (PAR): revisiting common chelating probe for the study of metalloproteins.,” Journal of inorganic biochemistry, vol. 152, pp. 82-92, 2015. doi:10.1016/j.jinorgbio.2015.08.024
    [Abstract]

    {4-(2-Pyridylazo})resorcinol ({PAR}) is one of the most popular chromogenic chelator used in the determination of the concentrations of various metal ions from the d, p and f blocks and their affinities for metal ion-binding biomolecules. The most important characteristics of such a sensor are the molar absorption coefficient and the metal-ligand complex dissociation constant. However, it must be remembered that these values are dependent on the specific experimental conditions (e.g. {pH}, solvent components, and reactant ratios). If one uses these values to process data obtained in different conditions, the final result can be under- or overestimated. We aimed to establish the spectral properties and the stability of {PAR} and its complexes accurately with Zn(2+), Cd(2+), Hg(2+), Co(2+), Ni(2+), Cu(2+), Mn(2+) and Pb(2+) at a multiple {pH} values. The obtained results account for the presence of different species of {metal-PAR} complexes in the physiological {pH} range of 5 to 8 and have been frequently neglected in previous studies. The effective molar absorption coefficient at 492 nm for the {ZnHx}({PAR})2 complex at {pH7}.4 in buffered water solution is 71,500 M(-1) cm(-1), and the dissociation constant of the complex in these conditions is 7.08×10(-13) M(2). To confirm these values and estimate the range of the dissociation constants of zinc-binding biomolecules that can be measured using {PAR}, we performed several titrations of zinc finger peptides and zinc chelators. Taken together, our results provide the updated parameters that are applicable to any experiment conducted using inexpensive and commercially available {PAR}. Copyright {\copyright} 2015 Elsevier Inc. All rights reserved.

    @article{citeulike:14145585,
    abstract = {{4-(2-Pyridylazo})resorcinol ({PAR}) is one of the most popular chromogenic chelator used in the determination of the concentrations of various metal ions from the d, p and f blocks and their affinities for metal ion-binding biomolecules. The most important characteristics of such a sensor are the molar absorption coefficient and the metal-ligand complex dissociation constant. However, it must be remembered that these values are dependent on the specific experimental conditions (e.g. {pH}, solvent components, and reactant ratios). If one uses these values to process data obtained in different conditions, the final result can be under- or overestimated. We aimed to establish the spectral properties and the stability of {PAR} and its complexes accurately with Zn(2+), Cd(2+), Hg(2+), Co(2+), Ni(2+), Cu(2+), Mn(2+) and Pb(2+) at a multiple {pH} values. The obtained results account for the presence of different species of {metal-PAR} complexes in the physiological {pH} range of 5 to 8 and have been frequently neglected in previous studies. The effective molar absorption coefficient at 492 nm for the {ZnHx}({PAR})2 complex at {pH7}.4 in buffered water solution is 71,500 M(-1) cm(-1), and the dissociation constant of the complex in these conditions is 7.08×10(-13) M(2). To confirm these values and estimate the range of the dissociation constants of zinc-binding biomolecules that can be measured using {PAR}, we performed several titrations of zinc finger peptides and zinc chelators. Taken together, our results provide the updated parameters that are applicable to any experiment conducted using inexpensive and commercially available {PAR}. Copyright {\copyright} 2015 Elsevier Inc. All rights reserved.},
    author = {Kocy{\l}a, Anna and Pomorski, Adam and Krę\.{z}el, Artur},
    citeulike-article-id = {14145585},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jinorgbio.2015.08.024},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26364130},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26364130},
    doi = {10.1016/j.jinorgbio.2015.08.024},
    issn = {1873-3344},
    journal = {Journal of inorganic biochemistry},
    month = nov,
    pages = {82--92},
    pmid = {26364130},
    posted-at = {2016-09-24 17:31:15},
    priority = {2},
    title = {Molar absorption coefficients and stability constants of metal complexes of 4-(2-pyridylazo)resorcinol ({PAR}): Revisiting common chelating probe for the study of metalloproteins.},
    url = {http://dx.doi.org/10.1016/j.jinorgbio.2015.08.024},
    volume = {152},
    year = {2015}
    }

  • V. Kloubert and L. Rink, “Zinc as a micronutrient and its preventive role of oxidative damage in cells.,” Food & function, vol. 6, iss. 10, pp. 3195-3204, 2015. doi:10.1039/C5FO00630A
    [Abstract]

    Zinc is an essential trace element with special importance in the immune system. Deficiencies of zinc are seen in the course of ageing and in various diseases, such as diabetes mellitus or rheumathoid arthritis. The trace element is essential for a variety of basic cellular functions and especially important for various enzymes participating in the production and neutralization of reactive oxygen species ({ROS}) which are normally produced by the cell. Under normal conditions {ROS} are neutralized and are not able to harm the cell, but in case of {ROS} elevation, oxidative damage within the cell is the result. Interestingly, zinc deficiency is directly associated with oxidative stress. Thus, control and regulation of the intracellular zinc content is essential with participation of various transporter and zinc-binding proteins, such as metallothionein. Oxidative stress is mainly caused by elevated {ROS} production and a decrease of antioxidant mechanisms. Zinc partly functions as an antioxidant although it is redox inert. Zinc supplementation is associated with decreased {ROS} formation exhibiting beneficial effects especially in ageing and diabetes mellitus. This review summarizes current findings concerning zinc as a micronutrient and its actions as a pro-antioxidant, and the association between zinc and oxidative stress under various conditions is highlighted.

    @article{citeulike:14145579,
    abstract = {Zinc is an essential trace element with special importance in the immune system. Deficiencies of zinc are seen in the course of ageing and in various diseases, such as diabetes mellitus or rheumathoid arthritis. The trace element is essential for a variety of basic cellular functions and especially important for various enzymes participating in the production and neutralization of reactive oxygen species ({ROS}) which are normally produced by the cell. Under normal conditions {ROS} are neutralized and are not able to harm the cell, but in case of {ROS} elevation, oxidative damage within the cell is the result. Interestingly, zinc deficiency is directly associated with oxidative stress. Thus, control and regulation of the intracellular zinc content is essential with participation of various transporter and zinc-binding proteins, such as metallothionein. Oxidative stress is mainly caused by elevated {ROS} production and a decrease of antioxidant mechanisms. Zinc partly functions as an antioxidant although it is redox inert. Zinc supplementation is associated with decreased {ROS} formation exhibiting beneficial effects especially in ageing and diabetes mellitus. This review summarizes current findings concerning zinc as a micronutrient and its actions as a pro-antioxidant, and the association between zinc and oxidative stress under various conditions is highlighted.},
    author = {Kloubert, Veronika and Rink, Lothar},
    citeulike-article-id = {14145579},
    citeulike-linkout-0 = {http://dx.doi.org/10.1039/C5FO00630A},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26286461},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26286461},
    doi = {10.1039/C5FO00630A},
    issn = {2042-650X},
    journal = {Food \& function},
    month = oct,
    number = {10},
    pages = {3195--3204},
    pmid = {26286461},
    posted-at = {2016-09-24 17:22:55},
    priority = {2},
    title = {Zinc as a micronutrient and its preventive role of oxidative damage in cells.},
    url = {http://dx.doi.org/10.1039/C5FO00630A},
    volume = {6},
    year = {2015}
    }

  • E. Rosenkranz, R. D. Hilgers, P. Uciechowski, A. Petersen, B. Plümäkers, and L. Rink, “Zinc enhances the number of regulatory t cells in allergen-stimulated cells from atopic subjects.,” European journal of nutrition, 2015. doi:10.1007/s00394-015-1100-1
    [Abstract]

    The trace element zinc is essential for immune function and its regulation. Since zinc deficiency and allergic hyperresponsive reactions are often accompanied, the influence of zinc on allergen-induced cell growth, {CD4}+ regulatory T (Treg) cell numbers and cytokine expression during allergic immune reactions was investigated. Peripheral blood mononuclear cells ({PBMCs}) from non-atopic and atopic subjects were treated with timothy grass allergen pre-incubated with or without zinc. Proliferation was determined by analyzing the incorporation of ({3)H}-thymidine. Intracellular zinc and Foxp3 levels and cell surface antigens were measured by {FACS}, cytokine expression by {ELISA} and real-time {PCR}. Incubation with 50 {μM} zinc sulfate (Zn50) enhances cytosolic zinc concentrations in {CD3}+ T cells. The data also reveal that the combination of Zn50 plus allergen significantly reduces {PBMC} proliferation of atopic subjects. Additionally, Zn50 plus allergen enhances Th1 cytokine responses shown by increased interferon ({IFN})-γ/interleukin ({IL})-10 ratios as well as enhanced tumor necrosis factor-α release. In response to allergen, zinc increases Treg cells and upregulates the {mRNA} expression of cytotoxic T-lymphocyte antigen-4 in atopic subjects. Interestingly, Zn50 alone leads to an increase of {CD4}+{CD25high}(hi)+ cells in atopic and non-atopic subjects. Zinc may regulate unwanted hyperresponsive immune reactions by suppressing proliferation through a significant shift from {IL}-10 to the Th1 cytokine {IFN}-γ, and enhanced regulatory T cell numbers. Therefore, zinc supplementation may be a promising tool for the therapy of allergies, without negatively affecting the immune system.

    @article{citeulike:14145576,
    abstract = {The trace element zinc is essential for immune function and its regulation. Since zinc deficiency and allergic hyperresponsive reactions are often accompanied, the influence of zinc on allergen-induced cell growth, {CD4}+ regulatory T (Treg) cell numbers and cytokine expression during allergic immune reactions was investigated. Peripheral blood mononuclear cells ({PBMCs}) from non-atopic and atopic subjects were treated with timothy grass allergen pre-incubated with or without zinc. Proliferation was determined by analyzing the incorporation of ({3)H}-thymidine. Intracellular zinc and Foxp3 levels and cell surface antigens were measured by {FACS}, cytokine expression by {ELISA} and real-time {PCR}. Incubation with 50 {μM} zinc sulfate (Zn50) enhances cytosolic zinc concentrations in {CD3}+ T cells. The data also reveal that the combination of Zn50 plus allergen significantly reduces {PBMC} proliferation of atopic subjects. Additionally, Zn50 plus allergen enhances Th1 cytokine responses shown by increased interferon ({IFN})-γ/interleukin ({IL})-10 ratios as well as enhanced tumor necrosis factor-α release. In response to allergen, zinc increases Treg cells and upregulates the {mRNA} expression of cytotoxic T-lymphocyte antigen-4 in atopic subjects. Interestingly, Zn50 alone leads to an increase of {CD4}+{CD25high}(hi)+ cells in atopic and non-atopic subjects. Zinc may regulate unwanted hyperresponsive immune reactions by suppressing proliferation through a significant shift from {IL}-10 to the Th1 cytokine {IFN}-γ, and enhanced regulatory T cell numbers. Therefore, zinc supplementation may be a promising tool for the therapy of allergies, without negatively affecting the immune system.},
    author = {Rosenkranz, Eva and Hilgers, Ralf-Dieter D. and Uciechowski, Peter and Petersen, Arnd and Pl\"{u}m\"{a}kers, Birgit and Rink, Lothar},
    citeulike-article-id = {14145576},
    citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00394-015-1100-1},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26589301},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26589301},
    day = {20},
    doi = {10.1007/s00394-015-1100-1},
    issn = {1436-6215},
    journal = {European journal of nutrition},
    month = nov,
    pmid = {26589301},
    posted-at = {2016-09-24 17:18:37},
    priority = {2},
    title = {Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects.},
    url = {http://dx.doi.org/10.1007/s00394-015-1100-1},
    year = {2015}
    }

  • R. Giacconi, L. Costarelli, M. Malavolta, M. Cardelli, R. Galeazzi, F. Piacenza, N. Gasparini, A. Basso, E. Mariani, T. Fulop, L. Rink, G. Dedoussis, G. Herbein, J. Jajte, M. Provinciali, F. Busco, and E. Mocchegiani, “Effect of ZIP2 Gln/Arg/leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation.,” Biofactors (oxford, england), vol. 41, iss. 6, pp. 414-423, 2015. doi:10.1002/biof.1247
    [Abstract]

    Zinc dyshomeostasis may lead to an augmented production of proinflammatory cytokines promoting chronic inflammation and increasing the susceptibility to age-related diseases. Several studies suggest that the zinc transporter protein {ZIP2} may play a relevant role in the immune system especially during zinc deficiency, while a polymorphism on the coding region of {ZIP2} gene ({Gln/Arg}/Leu) has been associated with severe carotid artery disease. The aim of this study is to investigate the role of {ZIP2} {SNP} on zinc and inflammatory status in 1090 elderly healthy free-living subjects enrolled in the {ZincAge} project and to assess the effect of zinc supplementation on zinc status, inflammatory mediators, and zinc transporter expression depending on {ZIP2} genotype. {ZIP2} Leu- ({Arg43Arg}) carriers showed enhanced {IL}-6, {TNF}-α, and {RANTES} plasma levels associated with decreased free cytosolic zinc in {PBMCs} and an upregulation of zinc transporters {ZIP2}, {ZIP8}, and Znt1. Moreover, Leu- subjects displayed significant decrement of inflammatory mediators such as {MCP}-1, {TNF}-α, and {RANTES} following zinc supplementation. In summary, this investigation provides new evidence on the effect of {ZIP2} {Gln/Arg}/Leu polymorphism on proinflammatory mediators and zinc homeostasis in elderly population with a more pronounced anti-inflammatory effect of zinc supplementation in subjects carrying {ZIP2} Leu- ({Arg43Arg}) genotype. These novel findings could be useful in identifying elderly subjects who may benefit of zinc intervention to decrease the inflammatory status and to prevent or delay the development of age-related diseases. {\copyright} 2015 International Union of Biochemistry and Molecular Biology.

    @article{citeulike:14145362,
    abstract = {Zinc dyshomeostasis may lead to an augmented production of proinflammatory cytokines promoting chronic inflammation and increasing the susceptibility to age-related diseases. Several studies suggest that the zinc transporter protein {ZIP2} may play a relevant role in the immune system especially during zinc deficiency, while a polymorphism on the coding region of {ZIP2} gene ({Gln/Arg}/Leu) has been associated with severe carotid artery disease. The aim of this study is to investigate the role of {ZIP2} {SNP} on zinc and inflammatory status in 1090 elderly healthy free-living subjects enrolled in the {ZincAge} project and to assess the effect of zinc supplementation on zinc status, inflammatory mediators, and zinc transporter expression depending on {ZIP2} genotype. {ZIP2} Leu- ({Arg43Arg}) carriers showed enhanced {IL}-6, {TNF}-α, and {RANTES} plasma levels associated with decreased free cytosolic zinc in {PBMCs} and an upregulation of zinc transporters {ZIP2}, {ZIP8}, and Znt1. Moreover, Leu- subjects displayed significant decrement of inflammatory mediators such as {MCP}-1, {TNF}-α, and {RANTES} following zinc supplementation. In summary, this investigation provides new evidence on the effect of {ZIP2} {Gln/Arg}/Leu polymorphism on proinflammatory mediators and zinc homeostasis in elderly population with a more pronounced anti-inflammatory effect of zinc supplementation in subjects carrying {ZIP2} Leu- ({Arg43Arg}) genotype. These novel findings could be useful in identifying elderly subjects who may benefit of zinc intervention to decrease the inflammatory status and to prevent or delay the development of age-related diseases. {\copyright} 2015 International Union of Biochemistry and Molecular Biology.},
    author = {Giacconi, Robertina and Costarelli, Laura and Malavolta, Marco and Cardelli, Maurizio and Galeazzi, Roberta and Piacenza, Francesco and Gasparini, Nazzarena and Basso, Andrea and Mariani, Erminia and Fulop, Tamas and Rink, Lothar and Dedoussis, George and Herbein, Georges and Jajte, Jolanta and Provinciali, Mauro and Busco, Franco and Mocchegiani, Eugenio},
    citeulike-article-id = {14145362},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/biof.1247},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26643924},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26643924},
    doi = {10.1002/biof.1247},
    issn = {1872-8081},
    journal = {BioFactors (Oxford, England)},
    number = {6},
    pages = {414--423},
    pmid = {26643924},
    posted-at = {2016-09-23 22:12:00},
    priority = {2},
    title = {Effect of {ZIP2} {Gln/Arg}/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation.},
    url = {http://dx.doi.org/10.1002/biof.1247},
    volume = {41},
    year = {2015}
    }

  • M. Warthon-Medina, P. Qualter, N. Zavaleta, S. Dillon, F. Lazarte, and N. M. Lowe, “The long term impact of micronutrient supplementation during infancy on cognition and executive function performance in Pre-School children.,” Nutrients, vol. 7, iss. 8, pp. 6606-6627, 2015. doi:10.3390/nu7085302
    [Abstract]

    Brain growth and development are critically dependent on several micronutrients. During early development cellular activity may be sensitive to micronutrient deficiencies, however the evidence from human studies is equivocal. The objective of this study was to examine the long-term cognitive and social-emotional effects of multiple micronutrient supplementation compared with iron supplementation alone, administered during infancy. This study was a follow-up to an initial randomized, double-blind controlled trial ({RCT}) in 2010 in which 902 infants, aged 6-17 months, from Lima, Peru, were given daily supplements of either iron (Fe) or multiple micronutrients ({MMN}) including zinc (451 in each group). The supplementation period for both groups was six months. In 2012, a subsample of 184 children from the original cohort (now aged 36-48 months) was randomly selected to participate in a follow-up trial and was assessed for intelligence, working memory, inhibition, and executive function. The tests showed no significant differences between the supplementation groups though there were some gender differences, with girls displaying higher scores than boys across both groups on the Wechsler Preschool and Primary Scale of Intelligence ({WPPSI}) Verbal {IQ} sentences subtest, the {Day-Night} cognitive test and on the Brief {Infant-Toddler} Social Emotional Assessment ({BITSEA}) social competency, and boys scoring higher than girls in problem behaviour. The results indicate that {MMN} supplementation had no long term additional effects on cognitive function compared with iron supplementation alone. The timing of supplement administration for maximum impact on a child’s cognitive development requires further investigation.

    @article{citeulike:14145336,
    abstract = {Brain growth and development are critically dependent on several micronutrients. During early development cellular activity may be sensitive to micronutrient deficiencies, however the evidence from human studies is equivocal. The objective of this study was to examine the long-term cognitive and social-emotional effects of multiple micronutrient supplementation compared with iron supplementation alone, administered during infancy. This study was a follow-up to an initial randomized, double-blind controlled trial ({RCT}) in 2010 in which 902 infants, aged 6-17 months, from Lima, Peru, were given daily supplements of either iron (Fe) or multiple micronutrients ({MMN}) including zinc (451 in each group). The supplementation period for both groups was six months. In 2012, a subsample of 184 children from the original cohort (now aged 36-48 months) was randomly selected to participate in a follow-up trial and was assessed for intelligence, working memory, inhibition, and executive function. The tests showed no significant differences between the supplementation groups though there were some gender differences, with girls displaying higher scores than boys across both groups on the Wechsler Preschool and Primary Scale of Intelligence ({WPPSI}) Verbal {IQ} sentences subtest, the {Day-Night} cognitive test and on the Brief {Infant-Toddler} Social Emotional Assessment ({BITSEA}) social competency, and boys scoring higher than girls in problem behaviour. The results indicate that {MMN} supplementation had no long term additional effects on cognitive function compared with iron supplementation alone. The timing of supplement administration for maximum impact on a child's cognitive development requires further investigation.},
    author = {Warthon-Medina, Marisol and Qualter, Pamela and Zavaleta, Nelly and Dillon, Stephanie and Lazarte, Fabiola and Lowe, Nicola M.},
    citeulike-article-id = {14145336},
    citeulike-linkout-0 = {http://dx.doi.org/10.3390/nu7085302},
    citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/26262642},
    citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=26262642},
    doi = {10.3390/nu7085302},
    issn = {2072-6643},
    journal = {Nutrients},
    month = aug,
    number = {8},
    pages = {6606--6627},
    pmid = {26262642},
    posted-at = {2016-09-23 20:23:54},
    priority = {2},
    title = {The Long Term Impact of Micronutrient Supplementation during Infancy on Cognition and Executive Function Performance in {Pre-School} Children.},
    url = {http://dx.doi.org/10.3390/nu7085302},
    volume = {7},
    year = {2015}
    }