Skip to main content

Oxidative Stress-Induced Cell Damage in the CNS

A Proposal for a Final Common Pathway

  • Chapter
Metals and Oxidative Damage in Neurological Disorders

Abstract

The previous chapters in this book have reviewed the involvement of transition metals in diseases of the central nervous system. While each of the diseases described was unique in its symptoms, one common feature is present: Transition metals contribute to the pathological process by facilitating generation of reactive oxygen species (ROS). This concluding chapter will examine the cells and organelles at risk for oxidative damage and propose a final common pathway in neural pathogenesis of oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Albakri, Q., and Stuehr, D., 1996, Intracellular assembly of inducible NO synthase is limited by NO mediated changes in heme insertion and availability, J. Biol. Chem. 271:5414–5421.

    Article  PubMed  CAS  Google Scholar 

  • Ballatori, N., 1994, Glutathione mercaptides as transport forms of metals, Adv. Pharmacol. 27:271–298.

    Article  PubMed  CAS  Google Scholar 

  • Benkovic, S. A., and Connor, J. R., 1993, Ferritin, transferrin, and iron in selected regions of the adult and aged rat brain, J. Comp. Neurol. 338:97–113.

    Article  PubMed  CAS  Google Scholar 

  • Bolanos, J. P., Peuchen, S., Heales, S. J., Land, J. M., and Clark, J. B., 1994, Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes, J. Neurochem. 63:910–916.

    Article  PubMed  CAS  Google Scholar 

  • Bowern, N., Ramshaw, I. A., Clark, I. A., and Doherty, P. C., 1984, Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent, J. Exper. Med. 160:1532–1543.

    Article  CAS  Google Scholar 

  • Brown, G. C., 1995, Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase, FEBS Lett. 369:136–139.

    Article  PubMed  CAS  Google Scholar 

  • Brown, G. C., Bolanos, J. P., Heales, S. J., and Clark, J. B., 1995, Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration, Neurosci. Lett. 193:201–204.

    Article  PubMed  CAS  Google Scholar 

  • Coyle, J. T., and Puttfarcken, P., 1993, Oxidative stress, glutamate, and neurodegenerative disorders, Science 262:689–695.

    Article  PubMed  CAS  Google Scholar 

  • Devesa, A., O’Connor, J. E., Garcia, C., Puertes, I. R., and Vina, J. R., 1993, Glutathione metabolism in primary astrocyte cultures: Flow cytometric evidence of heterogeneous distribution of GSH content, Brain Res. 618:181–189.

    Article  PubMed  CAS  Google Scholar 

  • Dumuis, A., Sebben, M., Haynes, L., Pin, J. P., and Bockaert, J., 1988, NMDA receptors activate the arachidonic acid cascade system in striatal neurons, Nature 336:68–70.

    Article  PubMed  CAS  Google Scholar 

  • Flatmark, T., and Romslo, I., 1975, Energy-dependent accumulation of iron by isolated rat liver mitochondria. Requirement of reducing equivalents and evidence for a unidirectional flux of Fe(II) across the inner membrane, J. Biol. Chem. 250:6433–6438.

    PubMed  CAS  Google Scholar 

  • Freedman, J. H., Ciriolo, M. R., and Peisach, J., 1989, The role of glutathione in copper metabolism and toxicity, J. Biol. Chem. 264:5598–5605.

    PubMed  CAS  Google Scholar 

  • Gelman, B. B., Rodriguez-Wolf, M. G., Wen, J., Kumar, S., Campbell, G. R., and Herzog, N., 1992, Siderotic cerebral macrophages in the acquired immunodeficiency syndrome, Arch. Pathol. Lab. Med. 116:509–516.

    PubMed  CAS  Google Scholar 

  • Gotz, M. E., Kunig, G., Riederer, P., and Youdim, M. B., 1994, Oxidative stress: Free radical production in neural degeneration, Pharmacol. Therap. 63:37–122.

    Article  CAS  Google Scholar 

  • Halliwell, B., and Gutteridge, J., 1989, Free Radicals in Biology and Medicine, Clarendon Press, Oxford.

    Google Scholar 

  • Halliwell, B., Gutteridge, J. M., and Cross, C. E., 1992, Free radicals, antioxidants, and human disease: where are we now?, J. Lab. Clin. Med. 119:598–620.

    PubMed  CAS  Google Scholar 

  • Hartung, H. P., Schafer, B., Heininger, K., and Toyka, K. V., 1988, Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase, Ann. Neurol. 23:453–460.

    Article  PubMed  CAS  Google Scholar 

  • Kehrer, J. P., and Lund, L. G., 1994, Cellular reducing equivalents and oxidative stress, Free Rad. Biol. Med. 17:65–75.

    Article  PubMed  CAS  Google Scholar 

  • Kerper, L. E., Ballatori, N., and Clarkson, T. W., 1992, Methylmercury transport across the blood-brain barrier by an amino acid carrier, Am. J. Physiol. 262:R761–765.

    Google Scholar 

  • Kim, Y. S., and Kim, S. U., 1991, Oligodendroglial cell death induced by oxygen radicals and its protection by catalase, J. Neurosci. Res. 29:100–106.

    Article  PubMed  CAS  Google Scholar 

  • Lehninger, A. L., Vercesi, A., and Bababunmi, E. A., 1978, Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides, Proc. Natl. Acad. Sci. USA 75:1690–1694.

    Article  PubMed  CAS  Google Scholar 

  • Mantyh, P. W., Ghilardi, J. R., Rogers, S., DeMaster, E., Allen, C. J., Stimson, E. R., and Maggio, J. E., 1993, Aluminum, iron and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide, J. Neurochem. 61:1171–1174.

    Article  PubMed  CAS  Google Scholar 

  • Masini, A., Trenti, T., Ceccarelli, D., and Muscatello, U. 1987, The effect of a ferric iron complex on isolated rat-liver mitochondria. III. Mechanistic aspects of iron-induced calcium efflux, Biochim. Biophys. Acta 891:150–156.

    Article  PubMed  CAS  Google Scholar 

  • McKenna, O., Arnold, G., and Holtzman, E., 1976, Microperoxisome distribution in the central nervous system of the rat, Brain Res. 117:181–94.

    Article  PubMed  CAS  Google Scholar 

  • Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., and Beal, M. F., 1993, Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain, Ann. Neurol. 34(4):609–16.

    Article  PubMed  CAS  Google Scholar 

  • Meister, A., 1991, Glutathione deficiency produced by inhibition of its synthesis, and its reversal: Applications in research and therapy, Pharmacol. Therap. 51:155–194.

    Article  CAS  Google Scholar 

  • Mitrovic, B., Ignarro, L. J., Montestruque, S., Smoll, A., and Merrill, J. E., 1994, Nitric oxide as a potential pathological mechanism in demyelination: its differential effects on primary glial cells in vitro, Neuroscience 61:575–585.

    Article  PubMed  CAS  Google Scholar 

  • Mitrovic, B., Ignarro, L. J., Vinters, H. V., Akers, M. A., Schmid, I., Uittenbogaart, C., and Merrill, J. E., 1995, Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes, Neuroscience 65:531–539.

    Article  PubMed  CAS  Google Scholar 

  • Monteiro, H. P., and Winterbourn, C. C., 1989, 6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation, Biochem. Pharmacol. 38:4177–4182.

    Article  PubMed  CAS  Google Scholar 

  • Naveilhan, P., Neveu, I., Jehan, F., Baudet, C., Wion, D., and Brachet, P., 1994, Reactive oxygen species influence nerve growth factor synthesis in primary rat astrocytes, J. Neurochem. 62:2178–2186.

    Article  PubMed  CAS  Google Scholar 

  • Noble, P. G., Antel, J. P., and Yong, V. W., 1994, Astrocytes and catalase prevent the toxicity of catecholamines to oligodendrocytes, Brain Res. 633:83–90.

    Article  PubMed  CAS  Google Scholar 

  • O’Connor, E., Devesa, A., Garcia, C., Puertes, I. R., Pellin, A., and Vina, J. R., 1995, Biosynthesis and maintenance of GSH in primary astrocyte cultures: role of L-cystine and ascorbate, Brain Res. 680:157–163.

    Article  PubMed  Google Scholar 

  • Oka, A., Beliveau, M. J., Rosenberg, P. A., and Volpe, J. J., 1993, Vulnerability of Oligodendroglia in glutamate: Pharmacology, mechanisms and prevention, J. Neurosci. 13:1441–1453.

    PubMed  CAS  Google Scholar 

  • Oshino, N., and Chance, B., 1977, Properties of glutathione release observed during reduction of organic hydroperoxide, demethylation of aminopyrine and oxidation of some substances in perfused rat liver, and their implications for the physiological function of catalase, Biochem. J. 162:509–25.

    PubMed  CAS  Google Scholar 

  • Packer, M. A., and Murphy, M. P., 1995, Peroxynitrite formed by simultaneous nitric oxide and superoxide generation causes cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation, Eur. J. Biochem. 234:231–239.

    Article  PubMed  CAS  Google Scholar 

  • Pechan, P. A., Chowdhury, K., and Seifert, W., 1992, Free radicals induce gene expression of NGF and bFGF in rat astrocyte culture, Neuroreport 3:469–472.

    Article  PubMed  CAS  Google Scholar 

  • Radi, R., Rodriguez, M., Castro, L., and Telleri, R., 1994, Inhibition of mitochondrial electron transport by peroxynitrite, Arch. Biochem. Biophys. 308:89–95.

    Article  PubMed  CAS  Google Scholar 

  • Raps, S. P., Lai, J. C., Hertz, L., and Cooper, A. J., 1989, Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons, Brain Res. 493:398–401.

    Article  PubMed  CAS  Google Scholar 

  • Ravindranath, V., and Reed, D. J., 1990, Glutathione depletion and formation of glutathione-protein mixed disulfide following exposure of brain mitochondria to oxidative stress, Biochem. Biophys. Res. Commun. 169:1075–1079.

    Article  PubMed  CAS  Google Scholar 

  • Reif, D. W., and Simmons, R. D., 1990, Nitric oxide mediates iron release from ferritin, Arch. Biochem. Biophys. 283:537–541.

    Article  PubMed  CAS  Google Scholar 

  • Richter, C., and Kass, G. E., 1991, Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis, cell death, proliferation, and differentiation, Chem. Biol. Interact. 77:1–23.

    Article  PubMed  CAS  Google Scholar 

  • Richter, C., Theus, M., and Schlegel, J., 1990, Cyclosporine A inhibits mitochondrial pyridine nucleotide hydrolysis and calcium release, Biochem. Pharmacol. 40:779–782.

    Article  PubMed  CAS  Google Scholar 

  • Samokyszyn, V. M., Reif, D. W., Miller, D. M., and Aust, S. D., 1991, Effects of ceruloplasmin on superoxide-dependent iron release from ferritin and lipid peroxidation, Free Rad. Res. Commun. 12–13:153–159.

    Article  Google Scholar 

  • Satrustegui, J., and Richter, C., 1984, The role of hydroperoxides as calcium release agents in rat brain mitochondria, Arch. Biochem. Biophys. 233:736–740.

    Article  PubMed  CAS  Google Scholar 

  • Steinkuhler, C., Sapora, O., Carri, M. T., Nagel, W., Marcocci, L., Ciriolo, M. R., Weser, V., and Rotilio, G., 1991, Increase of Cu,Zn-superoxide dismutase activity during differentiation of human K562 cells involves activation by copper of a constantly expressed copper-deficient protein, J. Biol. Chem. 266:24580–24587.

    PubMed  CAS  Google Scholar 

  • Takemura, R., and Werb, Z., 1984, Secretory products of macrophages and their physiological functions, Am. J. Physiol. 246:C1–9.

    Google Scholar 

  • Volterra, A., Trotti, D., Tromba, C., Floridi, S., and Racagni, G., 1994, Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes, J. Neurosci. 14:2924–2932.

    PubMed  CAS  Google Scholar 

  • Werner, E. R., Werner-Felmayer, G., and Wachter, H., 1993, Tetrahydrobiopterin and cytokines, Proc. Soc. Exper. Biol. Med. 203:1–12.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Robb-Gaspers, S.J., Connor, J.R. (1997). Oxidative Stress-Induced Cell Damage in the CNS. In: Connor, J.R. (eds) Metals and Oxidative Damage in Neurological Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0197-2_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0197-2_18

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0199-6

  • Online ISBN: 978-1-4899-0197-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics