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Zinc Homeostasis and Brain Injury

  • Stefano Sensi
  • Erica Rockabrand
  • Israel Sekler

Cumulating evidence suggest that Zn2+ dys/homeostasis can play a major role in promoting brain injury in excitotoxic syndromes. Zn2+ homeostasis in the brain is regulated through highly dynamic pathways and is deeply connected with other major signaling pathways, such as NO- and MAP kinase-dependent systems. Zn2+ signaling in neurons and glia also interplays with proton and Ca2+ homeostasis. Zn2+ appears to promote injury with greater potency compared to Ca2+ and as such the cation may be an underappreciated mediator of excitotoxicity, which for many years has been described mainly as a Ca2+- dependent phenomenon.

Keywords

Traumatic Brain Injury Neuronal Injury Mossy Fiber Zinc Homeostasis Transient Global Ischemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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10. References

  1. Aizenman, E., Stout, A.K., Hartnett, K.A., Dineley, K.E., McLaughlin, B. and Reynolds, I.J., 2000, Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release. J. Neurochem. 75: 1878.PubMedGoogle Scholar
  2. Andrasi, E., Farkas, E., Scheibler, H., Reffy, A. and Bezur, L., 1995, Al, Zn, Cu, Mn and Fe levels in brain in Alzheimer's disease. Arch. Gerontol. Geriatr. 21: 89.PubMedGoogle Scholar
  3. Aniksztejn, L., Charton, G. and Ben-Ari, Y., 1987, Selective release of endogenous zinc from the hippocampal mossy fibers in situ. Brain Res. 404: 58.PubMedGoogle Scholar
  4. Arseniev, A., Schultze, P., Worgotter, E., Braun, W., Wagner, G., Vasak, M., Kagi, J.H. and Wuthrich, K., 1988, Three-dimensional structure of rabbit liver [Cd7]metallothionein-2a in aqueous solution determined by nuclear magnetic resonance. J. Mol. Biol. 201: 637.PubMedGoogle Scholar
  5. Assaf, S.Y. and Chung, S.H., 1984, Release of endogenous Zn2+ from brain tissue during activity. Nature 308: 734.PubMedGoogle Scholar
  6. Azriel-Tamir, H., Sharir, H., Schwartz, B. and Hershfinkel, M., 2004, Extracellular zinc triggers ERK-dependent activation of Na+/H+ exchange in colonocytes mediated by the zinc sensing receptor. J. Biol. Chem. 279: 51804.PubMedGoogle Scholar
  7. Beckmann, A.M. and Wilce, P.A., 1997, Egr transcription factors in the nervous system. Neurochem. Int. 31: 477.PubMedGoogle Scholar
  8. Bell, S.M., Schreiner, C.M., Schultheis, P.J., Miller, M.L., Evans, R.L., Vorhees, C.V., Shull, G.E. and Scott, W.J., 1999, Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures. Am. J. Physiol. 276: C788.PubMedGoogle Scholar
  9. Bennett, M.V.L., Pellegrini-Giampietro, D.E., Gorter, J.A., Aronica, E., Connor, J.A. and Zukin, R.S., 1996, The GluR2 hypothesis: Ca2+-permeable AMPA receptors in delayed neurodegeneration. Cold Spring Harb. Symp. Quant. Biol. 61: 373.Google Scholar
  10. Blasco-Ibanez, J.M., Poza-Aznar, J., Crespo, C., Marques-Mari, A.I., Gracia-Llanes, F.J. and Martinez-Guijarro, F.J., 2004, Chelation of synaptic zinc induces overexcitation in the hilar mossy cells of the rat hippocampus. Neurosci. Lett. 355: 101.PubMedGoogle Scholar
  11. Bonanni, L., Li, H., Jover, L., Yokota, H., Sensi, S.L., Zukin, S. and Jonas, E.A., 2004, Zinc-dependent multiconductance channel activity in mitochondria isolated from ischemic brain. In SFN Annual Meeting. 2004. San Diego, CA: Washington, DC: Society for Neuroscience.Google Scholar
  12. Bossy-Wetzel, E., Talantova, M.V., Lee, W.D., Scholzke, M.N., Harrop, A., Mathews, E., Gotz, T., Han, J., Ellisman, M.H., Perkins, G.A. and Lipton, S.A., 2004, Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels. Neuron 41: 351.PubMedGoogle Scholar
  13. Brown, A.M., Tummolo, D.M., Rhodes, K.J., Hofmann, J.R., Jacobsen, J.S. and Sonnenberg-Reines, J., 1997, Selective aggregation of endogenous beta-amyloid peptide and soluble amyloid precursor protein in cerebrospinal fluid by zinc. J. Neurochem. 69: 1204.PubMedGoogle Scholar
  14. Brown, A.M., Kristal, B.S., Effron, M.S., Shestopalov, A.I., Ullucci, P.A., Sheu, K.-F.R., Blass, J.P. and Cooper, A.J.L., 2000, Zn2+ inhibits alpha-ketoglutarate-stimulated mitochondrial respiration and the isolated alphaketoglutarate dehydrogenase complex. J. Biol. Chem. 275: 13441.PubMedGoogle Scholar
  15. Bullock, R., Zauner, A., Myseros, J.S., Marmarou, A., Woodward, J.J. and Young, H.F., 1995, Evidence for prolonged release of excitatory amino acids in severe human head trauma. Relationship to clinical events. Ann. N. Y. Acad. Sci. 765: 290.PubMedGoogle Scholar
  16. Burkle, A., 2005, Poly (ADP-ribose). The most elaborate metabolite of NAD+. FEBS J. 272: 4576.PubMedGoogle Scholar
  17. Burnet, F.M., 1981, A possible role of zinc in the pathology of dementia. Lancet 1: 186.PubMedGoogle Scholar
  18. Bush, A.I., Thesis. 1992 The University of Melbourne.Google Scholar
  19. Bush, A.I., 2003, Copper, zinc, and the metallobiology of Alzheimer disease. Alzheimer Dis. Assoc. Disord. 17: 147.Google Scholar
  20. Bush, A.I., Pettingell, W.H., Multhaup, G., d Paradis, M., Vonsattel, J.P., Gusella, J.F., Beyreuther, K., Masters, C.L. and Tanzi, R.E., 1994a, Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265: 1464.PubMedGoogle Scholar
  21. Bush, A.I., Pettingell, Jr. W.H., Paradis, M.D. and Tanzi, R.E., 1994b, Modulation of A beta adhesiveness and secretase site cleavage by zinc. J. Biol. Chem. 269: 12152.PubMedGoogle Scholar
  22. Canzoniero, L.M., Turetsky, D.M. and Choi, D.W., 1999, Measurement of intracellular free zinc concentrations accompanying zinc-induced neuronal death. J. Neurosci. 19: 31.Google Scholar
  23. Chao, Y. and Fu, D., 2004, Kinetic study of the antiport mechanism of an Escherichia coli zinc transporter, ZitB. J. Biol. Chem. 279: 12043.Google Scholar
  24. Cheng, C. and Reynolds, I.J., 1998, Calcium-sensitive fluorescent dyes can report increases in intracellular free zinc concentration in cultured forebrain neurons. J. Neurochem. 71: 2401.PubMedGoogle Scholar
  25. Cherny, R.A., Legg, J.T., McLean, C.A., Fairlie, D.P., Huang, X., Atwood, C.S., Beyreuther, K., Tanzi, R.E., Masters, C.L. and Bush, A.I., 1999, Aqueous dissolution of Alzheimer’s disease Abeta amyloid deposits by biometal depletion. J. Biol. Chem. 274: 23223.PubMedGoogle Scholar
  26. Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., Barnham, K.J., Volitakis, I., Fraser, F.W. et al., 2001, Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30: 665.PubMedGoogle Scholar
  27. Choi, D.W., Yokoyama, M. and Koh, J., 1988, Zinc neurotoxicity in cortical cell culture. Neuroscience 24: 67.PubMedGoogle Scholar
  28. Chu, X.P., Wemmie, J.A., Wang, W.Z., Zhu, X.M., Saugstad, J.A., Price, M.P., Simon, R.P. and Xiong, Z.G., 2004, Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J. Neurosci. 24: 8678.PubMedGoogle Scholar
  29. Clark, R.S., Schiding, J.K., Kaczorowski, S.L., Marion, D.W. and Kochanek, P.M., 1994, Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models. J. Neurotrauma 11: 499.PubMedGoogle Scholar
  30. Cohen-Kfir, E., Lee, W., Eskandari, S. and Nelson, N., 2005, Zinc inhibition of gamma-aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory and inhibitory neurotransmission. Proc. Natl Acad. Sci. USA 102: 6154.PubMedGoogle Scholar
  31. Cole, T.B., Robbins, C.A., Wenzel, H.J., Schwartzkroin, P.A. and Palmiter, R.D., 2000, Seizures and neuronal damage in mice lacking vesicular zinc. Epilepsy Res. 39: 153.PubMedGoogle Scholar
  32. Constantinidis, J., 1990, Alzheimer’s disease and the zinc theory. Encephale 16: 231.PubMedGoogle Scholar
  33. Constantinidis, J., 1991, The hypothesis of zinc deficiency in the pathogenesis of neurofibrillary tangles. Med. Hypotheses 35: 319.PubMedGoogle Scholar
  34. Cornett, C.R., Markesbery, W.R. and Ehmann, W.D., 1998, Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain. Neurotoxicology 19: 339.PubMedGoogle Scholar
  35. Corrigan, F.M., Reynolds, G.P. and Ward, N.I., 1993, Hippocampal tin, aluminum and zinc in Alzheimer’s disease. Biometals 6: 149.PubMedGoogle Scholar
  36. Danscher, G., Jensen, K.B., Frederickson, C.J., Kemp, K., Andreasen, A., Juhl, S., Stoltenberg, M. and Ravid, R., 1997, Increased amount of zinc in the hippocampus and amygdala of Alzheimer's diseased brains: a proton-induced X-ray emission spectroscopic analysis of cryostat sections from autopsy material. J. Neurosci. Methods 76: 53.PubMedGoogle Scholar
  37. David, J.C., Yamada, K.A., Bagwe, M.R. and Goldberg, M.P., 1996, AMPA receptor activation is rapidly toxic to cortical astrocytes when desensitization is blocked. J. Neurosci. 16: 200.PubMedGoogle Scholar
  38. Deibel, M.A., Ehmann, W.D. and Markesbery, W.R., 1996, Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress. J. Neurol. Sci. 143: 137.PubMedGoogle Scholar
  39. Dineley, K.E., Scanlon, J.M., Kress, G.J., Stout, A.K. and Reynolds, I.J., 2000, Astrocytes are more resistant than neurons to the cytotoxic effects of increased [Zn(2+)](i). Neurobiol. Dis. 7: 310.PubMedGoogle Scholar
  40. Dineley, K.E., Brocard, J.B. and Reynolds, I.J., 2002, Elevated intracellular zinc and altered proton homeostasis in forebrain neurons. Neuroscience 114: 439.PubMedGoogle Scholar
  41. Dineley, K.E., Votyakova, T.V. and Reynolds, I.J., 2003, Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration. J. Neurochem. 85: 563.PubMedGoogle Scholar
  42. Du, L., Zhang, X., Han, Y., Burke, N.A., Kochanek, P.M., Watkins, S.C., Graham, S.H., Carcillo, J.A., Szabo, C. and Clark, R.S.B., 2003, Intra-mitochondrial poly(adp-ribosylation) contributes to NAD+ depletion and cell death induced by oxidative stress. J. Biol. Chem. 278: 18426.PubMedGoogle Scholar
  43. Ebadi, M., Leuschen, M.P., El Refaey, H., Hamada, F.M. and Rojas, P., 1996, The antioxidant properties of zinc and metallothionein. Neurochem. Int. 29: 159.PubMedGoogle Scholar
  44. Eide, D.J., 2004, The SLC39 family of metal ion transporters. Pflugers Arch. 447: 796.PubMedGoogle Scholar
  45. Erickson, J.C., Hollopeter, G., Thomas, S.A., Froelick, G.J. and Palmiter, R.D., 1997, Disruption of the metallothionein-III gene in mice: analysis of brain zinc, behavior, and neuron vulnerability to metals, aging, and seizures. J. Neurosci. 17: 1271.PubMedGoogle Scholar
  46. Frederickson, C.J. and Bush, A.I., 2001, Synaptically released zinc: physiological functions and pathological effects. BioMetals 14: 353.PubMedGoogle Scholar
  47. Frederickson, C.J. and Moncrieff, D.W., 1994, Zinc-containing neurons. Biol. Signals 3: 127.PubMedGoogle Scholar
  48. Frederickson, C.J., Hernandez, M.D., Goik, S.A., Morton, J.D. and McGinty, J.F., 1988, Loss of zinc staining from hippocampal mossy fibers during kainic acid induced seizures: a histofluorescence study. Brain Res. 446: 383.PubMedGoogle Scholar
  49. Frederickson, C.J., Hernandez, M.D. and McGinty, J.F., 1989, Translocation of zinc may contribute to seizure-induced death of neurons. Brain Res. 480: 317.PubMedGoogle Scholar
  50. Frederickson, C.J., Koh, J.Y. and Bush, A.I., 2005, The neurobiology of zinc in health and disease. Nat. Rev. Neurosci. 6: 449.PubMedGoogle Scholar
  51. Friedlich, A.L., Lee, J.Y., van Groen, T., Cherny, R.A., Volitakis, I., Cole, T.B., Palmiter, R.D., Koh, J.Y. and Bush, A.I., 2004, Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer’s disease. J. Neurosci. 24: 3453.PubMedGoogle Scholar
  52. Fukahori, M. and Itoh, M., 1990, Effects of dietary zinc status on seizure susceptibility and hippocampal zinc content in the El (epilepsy) mouse. Brain Res. 529: 16.PubMedGoogle Scholar
  53. Gazaryan, I.G., Krasnikov, B.F., Ashby, G.A., Thorneley, R.N.F., Kristal, B.S. and Brown, A.M., 2002, Zinc is a potent inhibitor of thiol oxidoreductase activity and stimulates reactive oxygen species production by lipoamide dehydrogenase. J. Biol. Chem. 277: 10064.PubMedGoogle Scholar
  54. Gorter, J.A., Petrozzino, J.J., Aronica, E.M., Rosenbaum, D.M., Opitz, T., Bennett, M.V., Connor, J.A. and Zukin, R.S., 1997, Global ischemia induces downregulation of Glur2 mRNA and increases AMPA receptor-mediated Ca2+ influx in hippocampal CA1 neurons of gerbil. J. Neurosci. 17: 6179.PubMedGoogle Scholar
  55. Hellmich, H.L., Frederickson, C.J., DeWitt, D.S., Saban, R., Parsley, M.O., Stephenson, R., Velasco, M., Uchida, T., Shimamura, M. and Prough, D.S., 2004, Protective effects of zinc chelation in traumatic brain injury correlate with upregulation of neuroprotective genes in rat brain. Neurosci. Lett. 355: 221.PubMedGoogle Scholar
  56. Hershfinkel, M., Moran, A., Grossman, N. and Sekler, I., 2001, A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport. Proc. Natl Acad. Sci. USA 98:11749.PubMedGoogle Scholar
  57. Hidalgo, J., Aschner, M., Zatta, P. and Vasak, M., 2001, Roles of the metallothionein family of proteins in the central nervous system. Brain Res. Bull. 55: 133.PubMedGoogle Scholar
  58. Holtz, M.L., Craddock, S.D. and Pettigrew, L.C., 2001, Rapid expression of neuronal and inducible nitric oxide synthases during post-ischemic reperfusion in rat brain. Brain Res. 898: 49.PubMedGoogle Scholar
  59. Howell, G.A., Welch, M.G. and Frederickson, C.J., 1984, Stimulation-induced uptake and release of zinc in hippocampal slices. Nature 308: 736.PubMedGoogle Scholar
  60. Huang, X., Atwood, C.S., Moir, R.D., Hartshorn, M.A., Vonsattel, J.P., Tanzi, R.E. and Bush, A.I., 1997, Zinc-induced Alzheimer’s Abeta1-40 aggregation is mediated by conformational factors. J. Biol. Chem. 272: 26464.PubMedGoogle Scholar
  61. Ikeda, T., Kimura, K., Morioka, S. and Tamaki, N., 1980, Inhibitory effects of Zn2+ on muscle glycolysis and their reversal by histidine. J. Nutr. Sci. Vitaminol. 26: 357.PubMedGoogle Scholar
  62. Itoh, M. and Ebadi, M., 1982, The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures. Neurochem. Res. 7: 1287.PubMedGoogle Scholar
  63. Jeng, J.-M., Jia, Y., Bonanni, L. and Weiss, J.H., 2002, Divergent effects of pH on Zn2+ and Ca2+ flux through Ca2+-permeable AMPA/kainate channels (CAKR). In SFN Annual Meeting. 2002. Orlando, FL: Washington, DC: Society for Neuroscience.Google Scholar
  64. Jia, Y., Jeng, J.M., Sensi, S.L. and Weiss, J.H., 2002, Zn2+ currents are mediated by calcium-permeable AMPA/kainate channels in cultured murine hippocampal neurones, J. Physiol. 543: 35.PubMedGoogle Scholar
  65. Jiang, L.-J., Maret, W. and Vallee, B.L., 1998, The glutathione redox couple modulates zinc transfer from metallothionein to zinc-depleted sorbitol dehydrogenase. Proc. Natl. Acad. Sci. USA 95: 3483.PubMedGoogle Scholar
  66. Jiang, L.J., Vasak, M., Vallee, B.L. and Maret, W., 2000, Zinc transfer potentials of the alpha - and beta-clusters of metallothionein are affected by domain interactions in the whole molecule. Proc. Natl Acad. Sci. USA 97: 2503.PubMedGoogle Scholar
  67. Jiang, D., Sullivan, P.G., Sensi, S.L., Steward, O. and Weiss, J.H., 2001, Zn(2+) induces permeability transition pore opening and release of pro-apoptotic peptides from neuronal mitochondria. J. Biol. Chem. 276: 47524.PubMedGoogle Scholar
  68. Kägi, J.H.R., Suzuki, K.T., Imura, N. and Kimura, M., 1993, Metallothionein III. Birkhäuser, Basel. Kaiser, J., 1994, Alzheimer’s: could there be a zinc link? Science 265: 1365.Google Scholar
  69. Kaplan, D.R. and Miller, F.D., 2000, Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10: 381.PubMedGoogle Scholar
  70. Kerchner, G., Canzoniero, L., Yu, S., Ling, C. and Choi, D.W., 2000, Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurons. J. Physiol. 528: 39.PubMedGoogle Scholar
  71. Kiedrowski, L., Czyz A., Baranauskas, G., Li, X.F. and Lytton, J., 2004, Differential contribution of plasmalemmal Na/Ca exchange isoforms to sodium-dependent calcium influx and NMDA excitotoxicity in depolarized neurons. J. Neurochem. 90: 117.PubMedGoogle Scholar
  72. Kim, Y.H. and Koh, J.Y., 2002, The role of NADPH oxidase and neuronal nitric oxide synthase in zinc-induced poly(ADP-ribose) polymerase activation and cell death in cortical culture. Exp. Neurol. 177: 407.PubMedGoogle Scholar
  73. Kim, E.Y., Koh, J.Y., Kim, Y.H., Sohn, S., Joe, E. and Gwag, B.J., 1999a, Zn2+ entry produces oxidative neuronal necrosis in cortical cell cultures. Eur. J. Neurosci. 11: 327.PubMedGoogle Scholar
  74. Kim, Y.H., Kim, E.Y., Gwag, B.J., Sohn, S. and Koh, J.Y., 1999b, Zinc-induced cortical neuronal death with features of apoptosis and necrosis: mediation by free radicals. Neuroscience 89:175.PubMedGoogle Scholar
  75. Kleiner, D. and von Jagow, G., 1972, On the inhibition of mitochondrial electron transport by Zn(2+) ions. FEBS Lett. 20: 229.PubMedGoogle Scholar
  76. Kleiner, D., 1974, The effect of Zn2+ ions on mitochondrial electron transport. Arch. Biochem. Biophys. 165: 121.PubMedGoogle Scholar
  77. Koh, J.Y., Suh, S.W., Gwag, B.J., He, Y.Y., Hsu, C.Y. and Choi, D.W., 1996, The role of zinc in selective neuronal death after transient global cerebral ischemia. Science 272: 1013.PubMedGoogle Scholar
  78. Kresse, W., Sekler, I., Hoffmann, A., Peters, O., Nolte, C., Moran, A. and Kettenmann, H., 2005, Zinc ions are endogenous modulators of neurotransmitter-stimulated capacitative Ca2+ entry in both cultured and in situ mouse astrocytes. Eur. J. Neurosci. 21: 1626.PubMedGoogle Scholar
  79. Kroncke, K.D., Fehsel, K., Schmidt, T., Zenke, F.T., Dasting, I., Wesener, J.R., Bettermann, H., Breunig, K.D. and Kolb-Bachofen, V., 1994, Nitric oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9. Biochem. Biophys. Res. Commun. 200: 1105.PubMedGoogle Scholar
  80. Krotkiewska, B. and Banas, T., 1992, Interaction of Zn2+ and Cu2+ ions with glyceraldehyde-3-phosphate dehydrogenase from bovine heart and rabbit muscle. Int. J. Biochem. 24: 1501.PubMedGoogle Scholar
  81. Kukimoto, I., Hoshino, S., Kontani, K., Inageda, K., Nishina, H., Takahashi, K. and Katada, T., 1996, Stimulation of ADP-ribosyl cyclase activity of the cell surface antigen CD38 by zinc ions resulting from inhibition of its NAD+ glycohydrolase activity. Eur. J. Biochem. 239: 177.PubMedGoogle Scholar
  82. Langmade, S.J., Ravindra, R., Daniels, P.J. and Andrews, G.K., 2000, The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J. Biol. Chem. 275: 34803.PubMedGoogle Scholar
  83. Lee, J.Y., Mook-Jung, I. and Koh, J.Y., 1999, Histochemically reactive zinc in plaques of the Swedish mutant beta-amyloid precursor protein transgenic mice. J. Neurosci. 19: 10.PubMedGoogle Scholar
  84. Lee, J.Y., Cole, T.B., Palmiter, R.D. and Koh, J.Y., 2000, Accumulation of zinc in degenerating hippocampal neurons of ZnT3-null mice after seizures: evidence against synaptic vesicle origin. J. Neurosci. 20: 79.Google Scholar
  85. Lee, J.Y., Kim, Y.H. and Koh, J.Y., 2001, Protection by pyruvate against transient forebrain ischemia in rats. J. Neurosci. 21: 171.Google Scholar
  86. Lee, J.M., Zipfel, G.J., Park, K.H., He, Y.Y., Hsu, C.Y. and Choi, D.W., 2002a, Zinc translocation accelerates infarction after mild transient focal ischemia. Neuroscience 115: 871.PubMedGoogle Scholar
  87. Lee, J.Y., Cole, T.B., Palmiter, R.D., Suh, S.W. and Koh, J.Y., 2002b, Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc. Natl Acad. Sci. USA 99: 7705.PubMedGoogle Scholar
  88. Lee, J.Y., Kim, J.H., Palmiter, R.D. and Koh, J.Y., 2003, Zinc released from metallothionein-iii may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury. Exp. Neurol. 184: 337.PubMedGoogle Scholar
  89. Lee, J.Y., Friedman, J.E., Angel, I., Kozak, A. and Koh, J.Y., 2004, The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol. Aging 25: 1315.PubMedGoogle Scholar
  90. Lerma, J., Morales, M., Ibarz, J.M. and Somohano, F., 1994, Rectification properties and Ca2+ permeability of glutamate receptor channels in hippocampal cells. Eur. J. Neurosci. 6: 1080.PubMedGoogle Scholar
  91. Link, T.A. and von Jagow, G., 1995, Zinc ions inhibit the QP center of bovine heart mitochondrial bc1 complex by blocking a protonatable group. J. Biol. Chem. 270: 25001.PubMedGoogle Scholar
  92. Lipton, P., 1999, Ischemic cell death in brain neurons. Physiol. Rev. 79: 1431.PubMedGoogle Scholar
  93. Lobner, D., Canzoniero, L.M., Manzerra, P., Gottron, F., Ying, H., Knudson, M., Tian, M., Dugan, L.L., Kerchner, G.A., Sheline, C.T., Korsmeyer, S.J. and Choi, D.W., 2000, Zinc-induced neuronal death in cortical neurons. Cell. Mol. Biol. 46: 797.PubMedGoogle Scholar
  94. Lovell, M.A., Robertson, J.D., Teesdale, W.J., Campbell, J.L. and Markesbery, W.R., 1998, Copper, iron and zinc in Alzheimer’s disease senile plaques. J. Neurol. Sci. 158: 47.PubMedGoogle Scholar
  95. Lowenstein, D.H., Thomas, M.J., Smith, D.H. and McIntosh, T.K., 1992, Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J. Neurosci. 12: 4846.PubMedGoogle Scholar
  96. Luo, J., Chen, H., Kintner, D.B., Shull, G.E. and Sun, D., 2005, Decreased neuronal death in Na+/H+ exchanger isoform 1-null mice after in vitro and in vivo ischemia. J. Neurosci. 25: 11256.PubMedGoogle Scholar
  97. MacDiarmid, C.W., Milanick, M.A. and Eide, D.J., 2002, Biochemical properties of vacuolar zinc transport systems of Saccharomyces cerevisiae. J. Biol. Chem. 277: 39187.PubMedGoogle Scholar
  98. Malaiyandi, L.M., Vergun, O., Dineley, K.E. and Reynolds, I.J., 2005, Direct visualization of mitochondrial zinc accumulation reveals uniporter-dependent and -independent transport mechanisms. J. Neurochem. 93: 1242.PubMedGoogle Scholar
  99. Maret, W. and Vallee, B.L., 1998, Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc. Natl Acad. Sci. USA 95: 3478.PubMedGoogle Scholar
  100. Maret, W., 1994, Oxidative metal release from metallothionein via zinc-thiol/disulfide interchange. Proc. Natl Acad. Sci. USA 91: 237.PubMedGoogle Scholar
  101. Maret, W., 2001, Crosstalk of the group IIa and IIb metals calcium and zinc in cellular signaling. Proc. Natl Acad. Sci. USA 98: 12325.PubMedGoogle Scholar
  102. McLaughlin, B., Pal, S., Tran, M.P., Parsons, A.A., Barone, F.C., Erhardt, J.A. and Aizenman, E., 2001, P38 Activation is required upstream of potassium current enhancement and caspase cleavage in thiol oxidant-induced neuronal apoptosis. J. Neurosci. 21: 3303.PubMedGoogle Scholar
  103. Mitchell, C.L. and Barnes, M.I., 1993, Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path. Neurotoxicol. Teratol. 15: 165.PubMedGoogle Scholar
  104. Moncayo, J., de Freitas, G.R., Bogousslavsky, J., Altieri, M. and van Melle, G., 2000, Do transient ischemic attacks have a neuroprotective effect? Neurology 54: 2089.PubMedGoogle Scholar
  105. Namura, S., Iihara, K., Takami, S., Nagata, I., Kikuchi, H., Matsushita, K., Moskowitz, M.A., Bonventre, J.V. and Alessandrini, A., 2001, Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc. Natl Acad. Sci. USA 98: 11569.PubMedGoogle Scholar
  106. Nicholls, D.G. and Budd, S.L., 2000, Mitochondria and neuronal survival. Physiol. Rev. 80: 315.PubMedGoogle Scholar
  107. Nicholls, P. and Malviya, A.N., 1968, Inhibition of nonphosphorylating electron transfer by zinc. The problem of delineating interaction sites. Biochemistry 7: 305.PubMedGoogle Scholar
  108. Nicotera, P., Leist, M. and Ferrando-May, E., 1999, Apoptosis and necrosis: different execution of the same death. Biochem. Soc. Symp. 66: 69.PubMedGoogle Scholar
  109. Nilsson, P., Hillered, L., Olsson, Y., Sheardown, M.J. and Hansen, A.J., 1993, Regional changes in interstitial K+and Ca2+ levels following cortical compression contusion trauma in rats. J. Cereb. Blood. Flow. Metab. 13: 183.PubMedGoogle Scholar
  110. Nitzan, Y.B., Sekler, I., Hershfinkel, M., Moran, A. and Silverman, W.F., 2002, Postnatal regulation of ZnT-1 expression in the mouse brain. Brain Res. Dev. Brain Res. 137: 149.Google Scholar
  111. Noh, K.M., Kim, Y.H. and Koh, J.Y., 1999, Mediation by membrane protein kinase C of zinc-induced oxidative neuronal injury in mouse cortical cultures. J. Neurochem. 72: 1609.PubMedGoogle Scholar
  112. Noh, K.M., Yokota, H., Mashiko, T., Castillo, P.E., Zukin, R.S. and Bennett, M.V., 2005, Blockade of calcium-permeable AMPA receptors protects hippocampal neurons against global ischemia-induced death. Proc. Natl Acad. Sci. USA 102: 12230.PubMedGoogle Scholar
  113. Nolte, C., Gore, A., Sekler, I., Kresse, W., Hershfinkel, M., Hoffmann, A., Kettenmann, H. and Moran, A., 2004, ZnT-1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc. Glia 48: 145.PubMedGoogle Scholar
  114. Ohana, E., Segal, D., Palty, R., Ton-That, D., Moran, A., Sensi, S.L., Weiss, J.H., Hershfinkel, M. and Sekler, I., 2004, A sodium zinc exchange mechanism is mediating extrusion of zinc in Mammalian cells. J. Biol. Chem. 279: 4278.PubMedGoogle Scholar
  115. Opitz, T., Grooms, S.Y., Bennett, M.V., Zukin, R.S. and Optiz, T., 2000, Remodeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit composition in hippocampal neurons after global ischemia. Proc. Natl Acad. Sci. USA 97: 13360.PubMedGoogle Scholar
  116. Packer, L., Tritschler, H.J. and Wessel, K., 1997, Neuroprotection by the metabolic antioxidant -lipoic acid. Free Radic. Biol. Med. 22: 359.Google Scholar
  117. Palmiter, R.D. and Findley, S., 1995, Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J. 14: 639.PubMedGoogle Scholar
  118. Palmiter, R.D. and Huang, L., 2004, Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers. Pflugers Arch. 447: 744.PubMedGoogle Scholar
  119. Palmiter, R.D., Cole, T.B., Quaife, C.J. and Findley, S.D., 1996, ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc. Natl Acad. Sci. USA 93: 14934.PubMedGoogle Scholar
  120. Park, J.A. and Koh, J.-Y., 1999, Induction of an immediate early gene egr-1 by zinc through extracellular signal-regulated kinase activation in cortical culture. J. Neurochem. 73: 450.PubMedGoogle Scholar
  121. Park, J.A., Lee, J.Y., Sato, T.A. and Koh, J.Y., 2000, Co-induction of p75NTR and p75NTR-associated death executor in neurons after zinc exposure in cortical culture or transient ischemia in the rat. J. Neurosci. 20: 9096.PubMedGoogle Scholar
  122. Pei, Y.Q. and Koyama, I., 1986, Features of seizures and behavioral changes induced by intrahippocampal injection of zinc sulfate in the rabbit: a new experimental model of epilepsy. Epilepsia 27: 183.PubMedGoogle Scholar
  123. Pei, Y., Zhao, D., Huang, J. and Cao, L., 1983, Zinc-induced seizures: a new experimental model of epilepsy. Epilepsia 24: 169.PubMedGoogle Scholar
  124. Pellegrini-Giampietro, D.E., Gorter, J.A., Bennett, M.V. and Zukin, R.S., 1997, The GluR2 (GluR-B) hypothesis: Ca(2+)-permeable AMPA receptors in neurological disorders. Trends Neurosci. 20: 464.PubMedGoogle Scholar
  125. Persechini, A., McMillan, K. and Masters, B.S., 1995, Inhibition of nitric oxide synthase activity by Zn2+ ion. Biochemistry 34: 15091.PubMedGoogle Scholar
  126. Potocnik, F.C., van Rensburg, S.J., Park, C., Taljaard, J.J. and Emsley, R.A., 1997, Zinc and platelet membrane microviscosity in Alzheimer's disease. The in vivo effect of zinc on platelet membranes and cognition. S. Afr. Med. J. 87: 1116.PubMedGoogle Scholar
  127. Pulsinelli, W.A., Brierley, J.B. and Plum, F., 1982, Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann. Neurol. 11: 491.PubMedGoogle Scholar
  128. Robbins, A.H., McRee, D.E., Williamson, M., Collett, S.A., Xuong, N.H., Furey, W.F., Wang, B.C. and Stout, C.D., 1991, Refined crystal structure of Cd, Zn metallothionein at 2.0 A resolution. J. Mol. Biol. 221: 1269.PubMedGoogle Scholar
  129. Samudralwar, D.L., Diprete, C.C., Ni, B.F., Ehmann, W.D. and Markesbery, W.R., 1995, Elemental imbalances in the olfactory pathway in Alzheimer’s disease. J. Neurol. Sci. 130: 139.PubMedGoogle Scholar
  130. Saris, N.E. and Niva, K., 1994, Is Zn2+ transported by the mitochondrial calcium uniporter? FEBS Lett. 356: 195.PubMedGoogle Scholar
  131. Segal, D., Ohana, E., Besser, L., Hershfinkel, M., Moran, A. and Sekler, I., 2004, A role for ZnT-1 in regulating cellular cation influx. Biochem. Biophys. Res. Commun. 323: 1145.PubMedGoogle Scholar
  132. Sekler, I., Moran, A., Hershfinkel, M., Dori, A., Margulis, A., Birenzweig, N., Nitzan, Y. and Silverman, W.F., 2002, Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain. J. Comp. Neurol. 447: 201.PubMedGoogle Scholar
  133. Selkoe, D.J., 2004, Alzheimer disease: mechanistic understanding predicts novel therapies. Ann. Intern. Med. 140: 627.PubMedGoogle Scholar
  134. Sensi, S.L. and Jeng, J.M., 2004, Rethinking the excitotoxic ionic milieu: the emerging role of Zn(2+) in ischemic neuronal injury. Curr. Mol. Med. 4: 87PubMedGoogle Scholar
  135. Sensi, S.L., Canzoniero, L.M., Yu, S.P., Ying, H.S., Koh, J.Y., Kerchner, G.A. and Choi, D.W., 1997, Measurement of intracellular free zinc in living cortical neurons: routes of entry. J. Neurosci. 17: 9554.PubMedGoogle Scholar
  136. Sensi, S.L., Ton-That, D. and Weiss, J.H., 2002, Mitochondrial sequestration and Ca(2+)-dependent release of cytosolic Zn(2+) loads in cortical neurons. Neurobiol. Dis. 10: 100.PubMedGoogle Scholar
  137. Sensi, S.L., Ton-That, D., Sullivan, P.G., Jonas, E.A., Gee, K.R., Kaczmarek, L.K. and Weiss, J.H., 2003b, Modulation of mitochondrial function by endogenous Zn2+ pools. Proc. Natl. Acad. Sci. USA 100: 6157.PubMedGoogle Scholar
  138. Sensi, S.L., Ton-That, D., Weiss, J.H., Rothe, A. and Gee, K.R., 2003a, A new mitochondrial fluorescent zinc sensor. Cell Calcium 34: 281.PubMedGoogle Scholar
  139. Sensi, S.L., Yin, H.Z. and Weiss, J.H., 1999a, Glutamate triggers preferential Zn2+ flux through Ca2+ permeable AMPA channels and consequent ROS production. Neuroreport 10: 1723.PubMedGoogle Scholar
  140. Sensi, S.L., Yin, H.Z. and Weiss, J.H., 2000, AMPA/kainate receptor-triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction. Eur. J. Neurosci. 12: 3813.PubMedGoogle Scholar
  141. Sensi, S.L., Yin, H.Z., Carriedo, S.G., Rao, S.S. and Weiss, J.H., 1999b, Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. Proc. Natl Acad. Sci. USA 96: 2414.PubMedGoogle Scholar
  142. Sheline, C.T., Behrens, M.M. and Choi, D.W., 2000, Zinc-induced cortical neuronal death: contribution of energy failure attributable to loss of NAD(+) and inhibition of glycolysis. J. Neurosci. 20: 3139.PubMedGoogle Scholar
  143. Skulachev, V.P., Chistyakov, V.V., Jasaitis, A.A. and Smirnova, E.G., 1967, Inhibition of the respiratory chain by zinc ions. Biochem. Biophys. Res. Commun. 26: 1.PubMedGoogle Scholar
  144. Sloviter, R.S., 1985, A selective loss of hippocampal mossy fiber Timm stain accompanies granule cell seizure activity induced by perforant path stimulation. Brain Res. 330: 150.PubMedGoogle Scholar
  145. Smart, T.G., Hosie, A.M. and Miller P.S., 2004, Zn2+ ions: modulators of excitatory and inhibitory synaptic activity. Neuroscientist 10: 432.PubMedGoogle Scholar
  146. Suh, S.W., Chen, J.W., Motamedi, M., Bell, B., Listiak, K., Pons, N.F., Danscher, G. and Frederickson, C.J., 2000a, Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury. Brain Res. 852: 268.PubMedGoogle Scholar
  147. Suh, S.W., Jensen, K.B., Jensen, M.S., Silva, D.S., Kesslak, P.J., Danscher, G. and Frederickson, C.J., 2000b, Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer’s diseased brains. Brain Res. 852: 274.PubMedGoogle Scholar
  148. Suh, S.W., Thompson, R.B. and Frederickson, C.J., 2001, Loss of vesicular zinc and appearance of perikaryal zinc after seizures induced by pilocarpine. Neuroreport 12: 1523.PubMedGoogle Scholar
  149. Takeda, A., Hirate, M., Tamano, H., Nisibaba, D. and Oku, N., 2003, Susceptibility to kainate-induced seizures under dietary zinc deficiency. J. Neurochem. 85: 1575.PubMedGoogle Scholar
  150. Thompson, C.M., Markesbery, W.R., Ehmann, W.D., Mao, Y.X. and Vance, D.E., 1988, Regional brain trace-element studies in Alzheimer’s disease. Neurotoxicology 9: 1.PubMedGoogle Scholar
  151. Tonder, N., Johansen, F.F., Frederickson, C.J., Zimmer, J. and Diemer, N.H., 1990, Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat. Neurosci. Lett. 109: 247.PubMedGoogle Scholar
  152. Traynelis, S. and Cull-Candy, S., 1990, Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons. Nature 345: 347.PubMedGoogle Scholar
  153. Trendelenburg, G., Prass, K., Priller, J., Kapinya, K., Polley, A., Muselmann, C., Ruscher, K., Kannbley, U., Schmitt, O., Castell, S., Wiegand, F., Meisel, A., Rosenthal, A. and Dirnagl, U., 2002, Serial analysis of gene expression identifies metallothionein-II as major neuroprotective gene in mouse focal cerebral ischemia. J. Neurosci. 22: 5879.PubMedGoogle Scholar
  154. van Lookeren Campagne, M., Thibodeaux, H., van Bruggen, N., Cairns, B., Gerlai, R., Palmer, T., Williams, S.P. and Lowe, D.G., 1999, Evidence for a protective role of metallothionein-1 in focal cerebral ischemia. Proc. Natl Acad. Sci. USA 96: 12870.PubMedGoogle Scholar
  155. Weiss, J.H., Hartley, D.M., Koh, J.Y. and Choi, D.W., 1993, AMPA receptor activation potentiates zinc neurotoxicity. Neuron 10: 43.PubMedGoogle Scholar
  156. Wenstrup, D., Ehmann, W.D. and Markesbery, W.R., 1990, Trace element imbalances in isolated subcellular fractions of Alzheimer’s disease brains. Brain Res. 533: 125.PubMedGoogle Scholar
  157. Wudarczyk, J., Debska, G. and Lenartowicz, E., 1999, Zinc as an inducer of the membrane permeability transition in rat liver mitochondria. Arch. Biochem. Biophys. 363: 1.PubMedGoogle Scholar
  158. Xia, Y., Zhao, P., Xue, J., Gu, X.Q., Sun, X., Yao, H. and Haddad, G.G., 2003, Na+ channel expression and neuronal function in the Na+/H+ exchanger 1 null mutant mouse. J. Neurophysiol. 89: 229.PubMedGoogle Scholar
  159. Xiong, Z.G., Zhu, X.M., Chu, X.P., Minami, M., Hey, J., Wei, W.L., MacDonald, J.F., Wemmie, J.A., Price, M.P., Welsh, M.J. and Simon, R.P., 2004, Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118: 687.PubMedGoogle Scholar
  160. Yi, J.S., Lee, S.K., Sato, T.A. and Koh, J.Y., 2003, Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat. Neurosci. Lett. 347: 126.PubMedGoogle Scholar
  161. Yin, H.Z. and Weiss, J.H., 1995, Zn(2+) permeates Ca(2+) permeable AMPA/kainate channels and triggers selective neural injury. Neuroreport 6: 2553.PubMedGoogle Scholar
  162. Yin, H.Z., Sensi, S.L., Carriedo, S.G. and Weiss, J.H., 1999, Dendritic localization of Ca(2+)-permeable AMPA/kainate channels in hippocampal pyramidal neurons. J. Comp. Neurol. 409: 250.PubMedGoogle Scholar
  163. Yin, H.Z., Sensi, S.L., Ogoshi, F. and Weiss, J.H., 2002, Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose deprivation-induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons. J. Neurosci. 22: 1273.PubMedGoogle Scholar
  164. Ying, W., Han, S.-K., Miller, J.W. and Swanson, R.A., 1999, Acidosis potentiates oxidative neuronal death by multiple mechanisms. J. Neurochem. 73: 1549.PubMedGoogle Scholar
  165. Yokoyama, M., Koh, J. and Choi, D.W., 1986, Brief exposure to zinc is toxic to cortical neurons. Neurosci. Lett. 71: 351.PubMedGoogle Scholar
  166. Yu, S.P., Canzoniero, L.M. and Choi, D.W., 2001, Ion homeostasis and apoptosis. Curr. Opin. Cell. Biol. 13: 405.PubMedGoogle Scholar
  167. Yu, S.P., Yeh, C.H., Sensi, S.L., Gwag, B.J., Canzoniero, L.M., Farhangrazi, Z.S., Ying, H.S., Tian, M., Dugan, L.L. and Choi, D.W., 1997, Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 278: 114.PubMedGoogle Scholar
  168. Yu, S.W., Wang, H., Poitras, M.F., Coombs, C., Bowers, W.J., Federoff, H.J., Poirier, G.G., Dawson, T.M. and Dawson, V.L., 2002, Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297: 259.PubMedGoogle Scholar
  169. Zhang, Y., Wang, H., Li, J., Jimenez, D.A., Levitan, E.S., Aizenman, E. and Rosenberg, P.A., 2004, Peroxynitrite-induced neuronal apoptosis is mediated by intracellular zinc release and 12-lipoxygenase activation. J. Neurosci. 24: 10616.PubMedGoogle Scholar
  170. Zhang, Y., Wang, H., Li, J., Dong, L., Xu P., Chen, W., Neve, R.L., Volpe, J.J. and Rosenberg, P.A., 2006, Intracellular zinc release and ERK phosphorylation are required upstream of 12-lipoxygenase activation in peroxynitrite toxicity to mature rat oligodendrocytes. J. Biol. Chem. 281: 9460.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Stefano Sensi
    • 1
  • Erica Rockabrand
    • 2
  • Israel Sekler
    • 3
  1. 1.Molecular Neurology Unit, Center of Excellence on AgingUniversity"G.d'Annunzio"Italy
  2. 2.Dept. of NeurologyUniversity of California-IrvineIrvineUSA
  3. 3.Faculty of Health Sciences, Dept. of Physiology and The Slotowski Center of NeuroscienceBen Gurion UniversityIsrael

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