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Journal of Toxicology
Volume 2012 (2012), Article ID 373678, 12 pages
http://dx.doi.org/10.1155/2012/373678
Research Article

Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

Department of Neurosurgery, The Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USA

Received 26 March 2012; Revised 7 May 2012; Accepted 21 May 2012

Academic Editor: Y. James Kang

Copyright © 2012 Martyn A. Sharpe 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. T. Suneja and D. V. Belsito, “Thimerosal in the detection of clinically relevant allergic contact reactions,” Journal of the American Academy of Dermatology, vol. 45, no. 1, pp. 23–27, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. D. D. Clarke and L. Sokoloff, “Circulation and energy metabolism of the brain,” in Basic neurochemistry: molecular, cellular and medical aspects, G. J. Siegel, Ed., pp. 637–669, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 1999. View at Google Scholar
  3. S. S. Korshunov, V. P. Skulachev, and A. A. Starkov, “High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria,” FEBS Letters, vol. 416, no. 1, pp. 15–18, 1997. View at Publisher · View at Google Scholar · View at Scopus
  4. V. P. Skulachev, “Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms,” Molecular Aspects of Medicine, vol. 20, no. 3, pp. 139–184, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. M. A. Sharpe, S. J. Robb, and J. B. Clark, “Nitric oxide and Fenton/Haber-Weiss chemistry: nitric oxide is a potent antioxidant at physiological concentrations,” Journal of Neurochemistry, vol. 87, no. 2, pp. 386–394, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. V. C. Stewart, M. A. Sharpe, J. B. Clark, and S. J. R. Heales, “Astrocyte-derived nitric oxide causes both reversible and irreversible damage to the neuronal mitochondrial respiratory chain,” Journal of Neurochemistry, vol. 75, no. 2, pp. 694–700, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. J. H. T. Power and P. C. Blumbergs, “Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson's disease and dementia with Lewy bodies,” Acta Neuropathologica, vol. 117, no. 1, pp. 63–73, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Ishida, A. Nagai, S. Kobayashi, and S. U. Kim, “Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase,” Journal of Neuropathology and Experimental Neurology, vol. 65, no. 1, pp. 66–77, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. J. R. Liddell, S. R. Robinson, R. Dringen, and G. M. Bishop, “Astrocytes retain their antioxidant capacity into advanced old age,” Glia, vol. 58, no. 12, pp. 1500–1509, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. V. Calabrese, R. Sultana, G. Scapagnini et al., “Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease,” Antioxidants and Redox Signaling, vol. 8, no. 11-12, pp. 1975–1986, 2006. View at Google Scholar · View at Scopus
  11. J. Mimura, K. Kosaka, A. Maruyama et al., “Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes,” Journal of Biochemistry, vol. 150, no. 2, pp. 209–217, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. T. A. Sarafian, N. Rajper, B. Grigorian, A. Kim, and H. Shau, “Cellular antioxidant properties of human natural killer enhancing factor B,” Free Radical Research, vol. 26, no. 3, pp. 281–289, 1997. View at Google Scholar · View at Scopus
  13. J. E. Holley, J. Newcombe, P. G. Winyard, and N. J. Gutowski, “Peroxiredoxin V in multiple sclerosis lesions: predominant expression by astrocytes,” Multiple Sclerosis, vol. 13, no. 8, pp. 955–961, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Desagher, J. Glowinski, and J. Premont, “Astrocytes protect neurons from hydrogen peroxide toxicity,” Journal of Neuroscience, vol. 16, no. 8, pp. 2553–2562, 1996. View at Google Scholar · View at Scopus
  15. V. C. Stewart, R. Stone, M. E. Gegg et al., “Presyervation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase,” Journal of Neurochemistry, vol. 83, no. 4, pp. 984–991, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. E. Röhrdanz, G. Schmuck, S. Ohler, and R. Kahl, “The influence of oxidative stress on catalase and MnSOD gene transcription in astrocytes,” Brain Research, vol. 900, no. 1, pp. 128–136, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. J. L. Franco, T. Posser, P. R. Dunkley et al., “Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase,” Free Radical Biology and Medicine, vol. 47, no. 4, pp. 449–457, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. V. Branco, J. Canário, J. Lu, A. Holmgren, and C. Carvalho, “Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase,” Free Radical Biology and Medicine, vol. 52, no. 4, pp. 781–793, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. L. Barregard, D. Rekić, M. Horvat, L. Elmberg, T. Lundh, and O. Zachrisson, “Toxicokinetics of mercury after long-term repeated exposure to thimerosal-containing vaccine,” Toxicological Sciences, vol. 120, no. 2, pp. 499–506, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Bragadin, D. Marton, S. Manente, M. Grasso, and A. Toninello, “Methylmercury induces the opening of the permeability transition pore in rat liver mitochondria,” Journal of Inorganic Biochemistry, vol. 89, no. 1-2, pp. 159–162, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. A. J. Canty, P. W. Moors, and G. B. Deacon, “Octanol/water partition coefficients as a model system for assessing antidotes for methylmercury(II) poisoning, and for studying mercurials with medicinal applications,” Journal of Inorganic Biochemistry, vol. 22, no. 1, pp. 65–72, 1984. View at Publisher · View at Google Scholar · View at Scopus
  22. Z. Yin, E. Lee, M. Ni et al., “Methylmercury-induced alterations in astrocyte functions are attenuated by ebselen,” NeuroToxicology, vol. 32, no. 3, pp. 291–299, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. R. P. Mason, J. R. Reinfelder, and F. M. M. Morel, “Uptake, toxicity, and trophic transfer of mercury in a coastal diatom,” Environmental Science and Technology, vol. 30, no. 6, pp. 1835–1845, 1996. View at Publisher · View at Google Scholar · View at Scopus
  24. P. R. Rich, “A perspective on Peter Mitchell and the chemiosmotic theory,” Journal of Bioenergetics and Biomembranes, vol. 40, no. 5, pp. 407–410, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. R. Clayton, J. B. Clark, and M. Sharpe, “Cytochrome c release from rat brain mitochondria is proportional to the mitochondrial functional deficit: implications for apoptosis and neurodegenerative disease,” Journal of Neurochemistry, vol. 92, no. 4, pp. 840–849, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Y. Abramov, T. K. Smulders-Srinivasan, D. M. Kirby et al., “Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations,” Brain, vol. 133, pp. 797–807, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. R. K. Dagda, S. J. Cherra, S. M. Kulich, A. Tandon, D. Park, and C. T. Chu, “Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission,” Journal of Biological Chemistry, vol. 284, no. 20, pp. 13843–13855, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Lossi, S. Alasia, C. Salio, and A. Merighi, “Cell death and proliferation in acute slices and organotypic cultures of mammalian CNS,” Progress in Neurobiology, vol. 88, no. 4, pp. 221–245, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. N. Mori, A. Yasutake, and K. Hirayama, “Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity,” Archives of Toxicology, vol. 81, no. 11, pp. 769–776, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. G. Shanker, T. Syversen, J. L. Aschner, and M. Aschner, “Modulatory effect of glutathione status and antioxidants on methylmercury-induced free radical formation in primary cultures of cerebral astrocytes,” Molecular Brain Research, vol. 137, no. 1-2, pp. 11–22, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Whiteman, Y. Dogra, P. G. Winyard, and J. S. Armstrong, “Detection and measurement of reactive oxygen intermediates in mitochondria and cells,” Methods in Molecular Biology, vol. 476, pp. 28–49, 2009. View at Google Scholar · View at Scopus
  32. K. I. Setsukinai, Y. Urano, K. Kakinuma, H. J. Majima, and T. Nagano, “Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species,” Journal of Biological Chemistry, vol. 278, no. 5, pp. 3170–3175, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. K. Hensley, “Detection of protein carbonyls by means of biotin hydrazide-streptavidin affinity methods,” Methods in Molecular Biology, vol. 536, pp. 457–462, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. C. W. Scott, C. Sobotka-Briner, D. E. Wilkins et al., “Novel small molecule inhibitors of caspase-3 block cellular and biochemical features of apoptosis,” Journal of Pharmacology and Experimental Therapeutics, vol. 304, no. 1, pp. 433–440, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. D. S. Baskin, M. A. Widmayer, and M. A. Sharpe, “Quantification of DNase type I ends, DNase type II ends, and modified bases using fluorescently labeled ddUTP, terminal deoxynucleotidyl transferase, and formamidopyrimidine-DNA glycosylase,” BioTechniques, vol. 49, no. 1, pp. 505–512, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. D. S. Baskin, M. A. Widmayer, and M. A. Sharpe, “Quantification and calibration of images in fluorescence microscopy,” Analytical Biochemistry, vol. 404, no. 2, pp. 118–126, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. C. P. LeBel, S. F. Ali, and S. C. Bondy, “Deferoxamine inhibits methyl mercury-induced increases in reactive oxygen species formation in rat brain,” Toxicology and Applied Pharmacology, vol. 112, no. 1, pp. 161–165, 1992. View at Publisher · View at Google Scholar · View at Scopus
  38. M. E. Fitch, C. M. Chang, and T. G. Parslow, “The BH3 domain is required for caspase-independent cell death induced by Bax and oligomycin,” Cell Death and Differentiation, vol. 7, no. 4, pp. 338–349, 2000. View at Google Scholar · View at Scopus
  39. A. Naganuma, K. Miura, T. Tanaka-Kagawa et al., “Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity in hela cells,” Life Sciences, vol. 62, no. 12, pp. PL157–PL161, 1998. View at Publisher · View at Google Scholar · View at Scopus
  40. J. St-Pierre, J. A. Buckingham, S. J. Roebuck, and M. D. Brand, “Topology of superoxide production from different sites in the mitochondrial electron transport chain,” Journal of Biological Chemistry, vol. 277, no. 47, pp. 44784–44790, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. B. White, M. R. Smyth, J. D. Stuart, and J. F. Rusling, “Oscillating formation of 8-oxoguanine during DNA oxidation,” Journal of the American Chemical Society, vol. 125, no. 22, pp. 6604–6605, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. N. Krishnamurthy, J. G. Muller, C. J. Burrows, and S. S. David, “Unusual structural features of hydantoin lesions translate into efficient recognition by Escherichia coli Fpg,” Biochemistry, vol. 46, no. 33, pp. 9355–9365, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Arakawa, R. D. Bach, and T. Kimura, “Kinetic study of the interaction of methylmercury with the Fe2S2(SR)4 cluster of adrenodoxin,” Journal of the American Chemical Society, vol. 102, no. 22, pp. 6847–6849, 1980. View at Google Scholar · View at Scopus
  44. V. Glaser, E. M. Nazari, Y. M. R. Müller et al., “Effects of inorganic selenium administration in methylmercury-induced neurotoxicity in mouse cerebral cortex,” International Journal of Developmental Neuroscience, vol. 28, no. 7, pp. 631–637, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. T. E. King, “Stoichiometry of labile sulfide, nonheme iron and flavin in reconstitutively active succinate dehydrogenase from heart mitochondria,” Biochemical and Biophysical Research Communications, vol. 16, no. 6, pp. 511–515, 1964. View at Google Scholar · View at Scopus
  46. H. Girouard, A. D. Bonev, R. M. Hannah, A. Meredith, R. W. Aldrich, and M. T. Nelson, “Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 8, pp. 3811–3816, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. D. Harman, “Aging: a theory based on free radical and radiation chemistry,” Journal of Gerontology, vol. 11, no. 3, pp. 298–300, 1956. View at Google Scholar · View at Scopus
  48. D. Harman, “The biologic clock: the mitochondria?” Journal of the American Geriatrics Society, vol. 20, no. 4, pp. 145–147, 1972. View at Google Scholar · View at Scopus