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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 5828056, 12 pages
https://doi.org/10.1155/2017/5828056
Review Article

Metallothionein in Brain Disorders

1Laboratorio de Neuropatología Experimental, Instituto Nacional de Neurología y Neurocirugía MVS, Mexico City, Mexico
2Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía MVS, Mexico City, Mexico

Correspondence should be addressed to Marisela Méndez-Armenta; moc.liamtoh@atnemrazednemm

Received 26 April 2017; Revised 17 July 2017; Accepted 3 August 2017; Published 20 September 2017

Academic Editor: Isabel C. F. R. Ferreira

Copyright © 2017 Daniel Juárez-Rebollar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Margoshes and B. L. Vallee, “A cadmium protein from equine kidney cortex,” American Chemical Society, vol. 79, no. 17, pp. 4813-4814, 1957. View at Publisher · View at Google Scholar
  2. J. H. Kagi and B. L. Valle, “Metallothionein: a cadmium and zinc containing protein from equine renal cortex,” The Journal of Biological Chemistry, vol. 236, no. 9, pp. 2435–2442, 1961. View at Google Scholar
  3. J. Hidalgo, M. Aschner, P. Zatta, and M. Vašák, “Roles of the metallothionein family of proteins in the central nervous system,” Brain Research Bulletin, vol. 55, no. 2, pp. 133–145, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. N. Thirumoorthy, A. Shyam Sunder, K. Manisenthil Kumar, M. Senthil Kumar, G. Ganesh, and M. Chatterjee, “A review of metallothionein isoforms and their role in pathophysiology,” World Journal of Surgical Oncology, vol. 9, p. 54, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Nordberg and G. F. Nordberg, “Toxicological aspects of metallothionein,” Cellular and Molecular Biology, vol. 46, no. 2, pp. 451–463, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Vašák and G. Meloni, “Metallothionein structure and reactivity,” Metallothioneins in Biochemistry and Pathology, Chapter 1, pp. 3–26, 1st edition edition, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Vašák, “Advances in metallothionein structure and functions,” Journal of Trace Elements in Medicine and Biology, vol. 19, no. 1, pp. 13–17, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. A. T. Miles, G. M. Hawksworth, J. H. Beattie, and V. Rodilla, “Induction, regulation, degradation, and biological significance of mammalian metallothioneins,” Critical Reviews in Biochemistry and Molecular Biology, vol. 35, no. 1, pp. 35–70, 2000. View at Publisher · View at Google Scholar
  9. K. A. West, J. Hidalgo, D. Eddins, E. D. Levin, and M. Aschner, “Metallothionein in the central nervous system: roles in protection, regeneration and cognition,” Neurotoxicology, vol. 29, no. 3, pp. 489–503, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Vašák and G. Meloni, “Chemistry and biology of mammalian metallothioneins,” Journal of Biological Inorganic Chemistry, vol. 16, no. 7, pp. 1067–1078, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. R. K. Stankovic, R. S. Chung, and M. Penkowa, “Metallothioneins I and II: neuroprotective significance during CNS pathology,” The International Journal of Biochemistry & Cell Biology, vol. 39, no. 3, pp. 484–489, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Sakulsak, “Metallothionein: an overview on its metal homeostatic regulation in mammals,” International Journal of Morphology, vol. 30, no. 3, pp. 1007–1012, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. M. A. Lynes, J. Hidalgo, Y. Manso, L. Devisscher, D. Laukens, and D. A. Lawrence, “Metallothionein and stress combine to affect multiple organ systems,” Cell Stress & Chaperones, vol. 19, no. 5, pp. 605–611, 2014. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Kimura and T. Kambe, “The functions of metallothionein and ZIP and ZnT transporters: an overview and perspective,” International Journal of Molecular Sciences, vol. 17, no. 3, pp. 336–357, 2016. View at Publisher · View at Google Scholar · View at Scopus
  15. C. D. Klaassen, J. Liu, and S. Choudhuri, “Metallothionein: an intracellular protein to protect against cadmium toxicity,” Annual Review of Pharmacology and Toxicology, vol. 39, pp. 267–294, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. H. G. Andrews, K. D. Lee, R. Ravindra et al., “The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-1 expression in endoderm cells during early development,” The European Molecular Biology Organization Journal, vol. 20, no. 5, pp. 1114–1122, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. T. P. Dalton, L. Qingwen, D. Bittel, L. Liang, and G. K. Andrews, “Oxidative stress activates metal-responsive transcription factor-1 binding activity. Occupancy in vivo of metal response elements in the metallothionein-I gene promoter,” The Journal of Biological Chemistry, vol. 271, no. 42, pp. 26233–26241, 1996. View at Publisher · View at Google Scholar · View at Scopus
  18. R. D. Palmiter, “The elusive function of metallothioneins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 15, pp. 8428–8430, 1998. View at Publisher · View at Google Scholar · View at Scopus
  19. W. Maret, “The function of zinc metallothionein: a link between cellular zinc and redox state,” The Journal of Nutrition, vol. 130, Supplement 5, pp. S1455–S1458, 2000. View at Google Scholar
  20. S. Sharma, C. S. Moon, A. Khogali et al., “Biomarkers in Parkinson’s disease (recent update),” Neurochemistry International, vol. 63, no. 3, pp. 201–229, 2013. View at Publisher · View at Google Scholar · View at Scopus
  21. C. D. Klaassen, J. Liu, and B. A. Diwan, “Metallothionein protection of cadmium toxicity,” Toxicology and Applied Pharmacology, vol. 238, no. 3, pp. 215–220, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Penkowa, “Metallothioneins are multipurpose neuroprotectants during brain pathology,” The FEBS Journal, vol. 273, no. 9, pp. 1857–1870, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. J. Kang, “Metallothionein redox cycle and function,” Experimental Biology and Medicine, vol. 231, no. 9, pp. 1459–1467, 2006. View at Publisher · View at Google Scholar
  24. M. V. Kumari, M. Hiramatsu, and M. Ebadi, “Free radical scavenging actions of metallothionein isoforms I and II,” Free Radical Research, vol. 29, no. 2, pp. 93–101, 1998. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Ø. Pedersen, R. Jensen, D. S. Pedersen et al., “Metallothionein-I+II in neuroprotection,” BioFactors, vol. 35, no. 4, pp. 315–325, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Sato and M. Kondoh, “Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals,” The Tohoku Journal of Experimental Medicine, vol. 196, no. 1, pp. 9–22, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. J. W. Asmussen, M. L. V. Sperling, and M. Penkowa, “Intraneuronal signaling pathways of metallothionein,” Journal of Neuroscience Research, vol. 87, no. 13, pp. 2926–2293, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Kwon, S. M. Jeon, S. H. Hwang, J. H. Kim, and H. J. Cho, “Expression and functional role of metallothioneins I and II in the spinal cord in inflammatory and neuropathic pain models,” Brain Research, vol. 1523, pp. 37–48, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Inoue, H. Takano, A. Shimada et al., “Role of metallothionein in coagulatory disturbance and systemic inflammation induced by lipopolysaccharide in mice,” FASEB Journal, vol. 20, no. 3, pp. 533–535, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. T. Shamsi and S. Fatima, “Metallothionein: classification, biochemical features and clinical applications,” Journal of Proteins and Proteomics, vol. 5, no. 1, pp. 25–33, 2014. View at Google Scholar
  31. C. R. Santos, A. Martinho, T. Quintela, and I. Gonçalves, “Neuroprotective and neuroregenerative properties of metallothioneins,” IUBMB Life, vol. 64, no. 2, pp. 126–135, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. N. Nishimura, H. Nishimura, A. Ghaffar, and C. Tohyama, “Localization of metallothionein in the brain of rat and mouse,” The Journal of Histochemistry and Cytochemestry, vol. 40, no. 2, pp. 309–315, 1992. View at Publisher · View at Google Scholar
  33. K. Suzuki, K. Nakajima, N. Otaki, and M. Kimura, “Metallothionein in developing human brain,” Biological Signals, vol. 3, no. 4, pp. 188–192, 1994. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Ambjørn, J. W. Asmussen, M. Lindstam et al., “Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family,” Journal of Neurochemistry, vol. 104, no. 1, pp. 21–37, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. R. S. Chung, M. Penkowa, J. Dittmann et al., “Redefining the role of metallothionein within the injured brain: extracellular metallothioneins play an important role in the astrocyte-neuron response to injury,” The Journal of Biological Chemistry, vol. 283, no. 22, pp. 15349–15358, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Fitzgerald, P. Nairn, C. A. Bartlett, R. S. Chung, A. K. West, and L. D. Beazley, “Metallothionein-IIA promotes neurite growth via the megalin receptor,” Experimental Brain Research, vol. 183, no. 2, pp. 171–180, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. Uchida, K. Takio, K. Titani, Y. Ihara, and M. Tomonaga, “The growth inhibitory factor that is deficient in the Alzheimer’s disease brain is a 68 amino acid metallothionein-like protein,” Neuron, vol. 7, no. 2, pp. 337–347, 1991. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Hidalgo, “Metallothioneins and brain injury: what transgenic mice tell us,” Environmental Health and Preventive Medicine, vol. 9, no. 3, pp. 87–94, 2004. View at Publisher · View at Google Scholar
  39. M. Yamada, S. Hayashi, I. Hozumi, T. Inuzuka, S. Tsuji, and H. Takahashi, “Subcellular localization of growth inhibitory factor in rat brain: light and electron microscopic immunohistochemical studies,” Brain Research, vol. 735, no. 2, pp. 257–264, 1996. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Ebadi, P. L. Iversen, R. Hao et al., “Expression and regulation of brain metallothionein,” Neurochemistry International, vol. 27, no. 1, pp. 1–22, 1995. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Aschner, M. G. Cherian, C. D. Klaassen, R. D. Palmiter, J. C. Erickson, and A. I. Bush, “Metallothioneins in brain—the role in physiology and pathology,” Toxicology and Applied Pharmacology, vol. 142, no. 2, pp. 229–242, 1997. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Carrasco, M. Penkowa, M. Giralta et al., “Role of metallothionein-III following central nervous system damage,” Neurobiology of Disease, vol. 13, no. 1, pp. 22–36, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Scuderi, C. Stecca, A. Iacomino, and L. Steardo, “Role of astrocytes in major neurological disorders: the evidence and implications,” IUBMB Life, vol. 65, no. 12, pp. 957–961, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Penkowa, J. Camats, M. Giralt et al., “Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte-targeted interleukin-6 expression,” Glia, vol. 42, no. 3, pp. 287–306, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. C. B. Poulsen, M. Penkowa, R. Borup et al., “Brain response to traumatic brain injury in wild-type and interleukin-6 knockout mice: a microarray analysis,” Journal of Neurochemistry, vol. 92, no. 2, pp. 417–432, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. A. Quintana, M. Giralt, S. Rojas et al., “Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury,” Journal of Neuroscience Research, vol. 82, no. 5, pp. 701–716, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Valko, D. Leibfritz, J. Moncol, M. M. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological functions and human disease,” The International Journal of Biochemistry & Cell Biology, vol. 39, no. 1, pp. 44–84, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. J. H. Kim, Y. P. Nam, S. M. Jeon, H. S. Han, and K. Suk, “Amyloid neurotoxicity is attenuated by metallothionein: dual mechanisms at work,” Journal of Neurochemistry, vol. 121, no. 5, pp. 751–762, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Carrasco, P. Adlard, C. Cotman et al., “Metallothionein-I and -III expression in animal models of Alzheimer disease,” Neuroscience, vol. 143, no. 4, pp. 911–922, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Manoharan, G. J. Guillemin, R. S. Abiramasundari, M. M. Essa, M. Akbar, and M. D. Akbar, “The role of reactive oxygen species in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease: a mini review,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 8590578, 15 pages, 2016. View at Publisher · View at Google Scholar
  51. M. Ebadi, H. Brown-Borg, H. E. Refaey et al., “Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson’s disease,” Molecular Brain Research, vol. 134, no. 1, pp. 67–75, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Ebadi and S. Sharma, “Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease,” Experimental Biology and Medicine, vol. 231, no. 9, pp. 1576–1583, 2006. View at Publisher · View at Google Scholar
  53. A. Nunomura, P. I. Moreira, R. J. Castellani et al., “Oxidative damage to RNA in aging and neurodegenerative disorders,” Neurotoxicity Research, vol. 22, no. 3, pp. 231–248, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. D. P. Salmon, R. G. Thomas, M. M. Pay et al., “Alzheimer’s disease can be accurately diagnosed in very mildly impaired individuals,” Neurology, vol. 59, no. 7, pp. 1022–1028, 2002. View at Publisher · View at Google Scholar
  55. P. H. Reddy and M. F. Beal, “Are mitochondria critical in the pathogenesis of Alzheimer’s disease?” Brain Research Brain Research Reviews, vol. 49, no. 3, pp. 618–632, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. P. H. Reddy, “Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer’s disease,” Journal of Neurochemistry, vol. 96, no. 1, pp. 1–13, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. K. P. Kepp, “Bioinorganic chemistry of Alzheimer’s disease,” Chemical Reviews, vol. 112, no. 10, pp. 5193–5239, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. I. Hozumi, M. Asanuma, M. Yamada, and Y. Uchida, “Metallothioneins and neurodegenerative diseases,” Journal of Health Science, vol. 50, no. 4, pp. 323–331, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. L. M. Sayre, M. A. Smith, and G. Perry, “Chemistry and biochemistry of oxidative stress in neurodegenerative disease,” Current Medicinal Chemistry, vol. 8, no. 7, pp. 721–738, 2001. View at Publisher · View at Google Scholar
  60. D. L. Marcus, C. Thomas, C. Rodriguez et al., “Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease,” Experimental Neurology, vol. 150, no. 1, pp. 40–44, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. D. A. Butterfield and C. M. Lauderback, “Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress,” Free Radical Biology & Medicine, vol. 32, no. 11, pp. 1050–1060, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. D. A. Butterfield, “Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer’s disease brain. A review,” Free Radical Research, vol. 36, no. 12, pp. 1307–1313, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Behl, J. B. Davis, R. Lesley, and D. Schubert, “Hydrogen peroxide mediates amyloid β protein toxicity,” Cell, vol. 77, no. 6, pp. 817–827, 1994. View at Publisher · View at Google Scholar · View at Scopus
  64. F. Li, N. Y. Calingasan, F. Yu et al., “Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice,” Journal of Neurochemistry, vol. 89, no. 5, pp. 1308–1312, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. Zhao and B. Zhao, “Oxidative stress and the pathogenesis of Alzheimer’s disease,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 316523, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. M. P. Mattson, “Free radicals and disruption of neuronal ion homeostasis in AD: a role for amyloid beta-peptide?” Neurobiology of Aging, vol. 16, no. 4, pp. 679–682, 1995. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Manczak, T. S. Anekonda, E. Henson, B. S. Park, J. Quinn, and P. H. Reddy, “Mitochondria are a direct site of Aβ accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression,” Human Molecular Genetics, vol. 15, no. 9, pp. 1437–1449, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. P. Zambenedetti, R. Giordano, and P. Zatta, “Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer’s disease,” Journal of Chemical Neuroanatomy, vol. 15, no. 1, pp. 21–26, 1998. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Hidalgo, M. Penkowa, C. Espejo et al., “Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation,” Experimental Biology and Medicine, vol. 231, no. 9, pp. 1450–1458, 2006. View at Publisher · View at Google Scholar
  70. A. I. Bush, R. D. Moir, K. M. Rosenkranz, and R. E. Tanzi, “Zinc and Alzheimer’s disease,” Science, vol. 268, no. 5219, pp. 1921–1923, 1995. View at Publisher · View at Google Scholar
  71. M. A. Deibel, W. D. Ehmann, and W. R. Markesbery, “Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress,” Journal of the Neurological Science, vol. 143, no. 1-2, pp. 137–142, 1996. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Tsuji, H. Kobayashi, Y. Uchida, Y. Ihara, and T. Miyatake, “Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer’s disease,” The EMBO Journal, vol. 11, no. 13, pp. 4843–4850, 1992. View at Google Scholar
  73. W. H. Yu, W. J. Lukiw, C. Bergeron, H. B. Niznik, and P. E. Fraser, “Metallothionein III is reduced in Alzheimer’s disease,” Brain Research, vol. 894, no. 1, pp. 37–45, 2001. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Irie and W. M. Keung, “Anti-amyloid beta activity of metallothionein-III is different from its neuronal growth inhibitory activity: structure-activity studies,” Brain Research, vol. 960, no. 1-2, pp. 228–234, 2003. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Emre, D. Aarsland, A. Albanese et al., “Rivastigmine for dementia associated with Parkinson’s disease,” The New England Journal of Medicine, vol. 351, no. 24, pp. 2509–2518, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. G. DeMaagd and A. Philip, “Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis,” P & T : a Peer-Reviewed Journal for Formulary Management, vol. 40, no. 8, pp. 504–532, 2015. View at Google Scholar
  77. J. Massano and K. P. Bhatia, “Clinical approach to Parkinson’s disease: features, diagnosis, and principles of management,” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 6, article a008870, 2012. View at Publisher · View at Google Scholar · View at Scopus
  78. D. J. Surmeier, J. N. Guzman, J. Sanchez-Padilla, and P. T. Schumacker, “The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson’s disease,” Neuroscience, vol. 198, pp. 221–231, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. M. G. Spillantini, R. A. Crowther, R. Jakes, M. Hasegawa, and M. Goedert, “α-Synuclein in filamentous inclusions of lewy bodies from Parkinson’s disease and dementia with Lewy bodies,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 11, pp. 6469–6473, 1998. View at Publisher · View at Google Scholar · View at Scopus
  80. G. J. Michael, S. Esmailzadeh, L. B. Moran, L. Christian, R. K. Pearce, and M. B. Graeber, “Up-regulation of metallothionein gene expression in Parkinsonian astrocytes,” Neurogenetics, vol. 12, no. 4, pp. 295–305, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. I. Miyazaki, M. Asanuma, H. Hozumi, K. Miyoshi, and N. Sogawa, “Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity,” FEBS Letters, vol. 581, no. 25, pp. 5003–5008, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. I. Miyazaki, C. A. Sogawa, M. Asanuma et al., “Expression of metallothionein-III mRNA and its regulation by levodopa in the basal ganglia of hemi-parkinsonian rats,” Neuroscience Letters, vol. 293, no. 1, pp. 65–68, 2000. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Sharma and M. Ebadi, “Metallothioneins as early and sensitive biomarkers of redox signaling in neurodegenerative disorders,” IIOAB Journal, vol. 2, no. 6, pp. 98–106, 2011. View at Google Scholar
  84. A. Diaz-Ruiz, P. Vacio-Adame, A. Monroy-Noyola et al., “Metallothionein-II inhibits lipid peroxidation and improves functional recovery after transient brain ischemia and reperfusion in rats,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 436429, 7 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  85. U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends in Neuroscience, vol. 22, no. 9, pp. 391–397, 1999. View at Publisher · View at Google Scholar · View at Scopus
  86. J. Y. Koh, S. W. Suh, B. J. Gwag, Y. Y. He, C. Y. Hsu, and D. W. Choi, “The role of zinc in selective neuronal death after transient global cerebral ischemia,” Science, vol. 272, no. 5264, pp. 1013–1016, 1996. View at Publisher · View at Google Scholar
  87. P. T. Akins, P. K. Liu, and C. Y. Hsu, “Immediate early gene expression in response to cerebral ischemia. Friend or foe?” Stroke, vol. 27, no. 9, pp. 1682–1687, 1996. View at Publisher · View at Google Scholar
  88. M. van Lookeren Campagne, H. Thibodeaux, N. van Bruggen et al., “Evidence for a protective role of metallothionein-1 in focal cerebral ischemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 22, pp. 12870–12875, 1999. View at Publisher · View at Google Scholar · View at Scopus
  89. M. van Lookeren Campagne, H. Thibodeaux, N. van Bruggen, B. Cairns, and D. G. Lowe, “Increased binding activity at an antioxidant-responsive element in the metallothionein-1 promoter and rapid induction of metallothionein-1 and -2 in response to cerebral ischemia and reperfusion,” The Journal of Neuroscience, vol. 20, no. 14, pp. 5200–5207, 2000. View at Google Scholar
  90. G. Trendelenburg, K. Prass, J. Priller et al., “Serial analysis of gene expression identifies metallothionein-II as major neuroprotective gene in mouse focal cerebral ischemia,” The Journal of Neuroscience, vol. 22, no. 14, pp. 5879–5888, 2002. View at Google Scholar
  91. S. Yanagitani, H. Miyazaki, Y. Nakahashi et al., “Ischemia induces metallothionein III expression in neurons of rat brain,” Life Sciences, vol. 64, no. 8, pp. 707–715, 1999. View at Publisher · View at Google Scholar · View at Scopus
  92. A. Koumura, J. Hamanaka, M. Shimazawa et al., “Metallothionein-III knockout mice aggravates the neuronal damage after transient focal cerebral ischemia,” Brain Research, vol. 1292, pp. 148–154, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. K. Inoue, H. Takano, A. Shimada, and M. Satoh, “Metallothionein as an anti-inflammatory mediator,” Mediators of Inflammation, vol. 2009, Article ID 101659, 7 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. R. S. Chung, J. C. Vickers, M. I. Chuah, and A. K. West, “Metallothionein-IIA promotes initial neurite elongation and postinjury reactive neurite growth and facilitates healing after focal cortical brain injury,” The Journal of Neuroscience, vol. 23, no. 8, pp. 3336–3342, 2003. View at Google Scholar
  95. A. K. West, J. Y. Leung, and R. S. Chung, “Neuroprotection and regeneration by extracellular metallothionein via lipoprotein-receptor-related proteins,” Journal of Biological Inorganic Chemistry, vol. 16, no. 7, pp. 1115–1122, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. A. Eidizadeh, M. Khajehalichalehshtari, D. Freyer, and G. Trendelenburg, “Assessment of the therapeutic potential of metallothionein-II application in focal cerebral ischemia in vitro and in vivo,” PLoS One, vol. 10, no. 12, article e0144035, 2015. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Eidizadeh and G. Trendelenburg, “Focusing on the protective effects of metallothionein-I/II in cerebral ischemia,” Neural Regeneneration Research, vol. 11, no. 5, pp. 721-722, 2016. View at Publisher · View at Google Scholar · View at Scopus
  98. R. S. Fisher, W. van Emde Boas, W. Blume et al., “Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE),” Epilepsia, vol. 46, no. 4, pp. 470–472, 2005. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Waldbaum and M. Patel, “Mitochondrial oxidative stress in temporal lobe epilepsy,” Epilepsy Research, vol. 88, no. 1, pp. 23–45, 2010. View at Publisher · View at Google Scholar · View at Scopus
  100. Y. C. Chuang, “Mitochondrial dysfunction and oxidative stress in seizure-induced neuronal cell death,” Acta Neurologica Taiwanica, vol. 19, no. 1, pp. 3–15, 2010. View at Google Scholar
  101. D. Juárez-Rebollar, J. Manjarrez, C. Nava-Ruíz et al., “Metallothionein expression in the rat brain following KA and PTZ treatment,” Environmental Toxicology and Pharmacology, vol. 40, no. 2, pp. 530–534, 2015. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Kim, E. H. Kim, C. H. Kim et al., “Differential regulation of metallothionein-I, II, and III mRNA expression in the rat brain following kainic acid treatment,” Neuroreport, vol. 14, no. 5, pp. 679–682, 2003. View at Google Scholar
  103. J. Carrrasco, M. Penkowa, H. Hadberg, A. Molinero, and J. Hidalgo, “Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice,” The European Journal of Neuroscience, vol. 12, no. 7, pp. 2311–2322, 2000. View at Publisher · View at Google Scholar · View at Scopus
  104. M. Penkowa, S. Florit, M. Giralt et al., “Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures,” Journal of Neuroscience Research, vol. 79, no. 4, pp. 522–534, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. T. Anezaki, H. Ishiguro, I. Hozumi et al., “Expression of growth inhibitory factor (GIF) in normal and injured rat brains,” Neurochemistry International, vol. 27, no. 1, pp. 89–94, 1995. View at Publisher · View at Google Scholar · View at Scopus
  106. J. C. Erickson, G. Hollopeter, S. A. Thomas, G. J. Froelick, and R. D. Palmiter, “Disruption of the metallothionein-III gene in mice: analysis of brain zinc, behavior, and neuron vulnerability to metals, aging, and seizures,” The Journal of Neuroscience, vol. 17, no. 4, pp. 1271–1281, 1997. View at Google Scholar
  107. J. E. Peixoto-Santos, O. Y. Galvis-Alonso, T. Rodriguez-Velasco et al., “Increased metallothionein I/II expression in patients with temporal lobe epilepsy,” PLoS One, vol. 11, no. 7, article e0159122, 2016. View at Publisher · View at Google Scholar · View at Scopus
  108. D. Juárez-Rebollar, M. Alonso-Vanegas, C. Nava-Ruíz et al., “Immunohistochemical study of metallothionein in patients with temporal lobe epilepsy,” Journal of Clinical Neuroscience, vol. 39, pp. 87–90, 2017. View at Publisher · View at Google Scholar