Advertisement

Oxygen Toxicity Induces Apoptotic Neuronal Death in Cultured Rat Hippocampal Neurons

  • Yasushi Enokido
  • Tomoko Yonemasu
  • Takekazu Kubo
  • Masumi Ichikawa
  • Hiroshi Hatanaka
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)

Abstract

Oxygen metabolism is the most important event for the aerobic energy metabolism and the redox-based biosynthesis. This means that cells are constantly exposed to oxidative stress during their life. As a consequence of a normal aerobic metabolism, several oxidants such as O 2 , H2O2 and ·OH are produced by successive additions of electrons to O2. These byproducts cause ubiquitous cell damage and are thought to contribute to aging and to degenerative diseases (Ames, et al., 1993). It is well-known that the brain is one of the most energy consuming organs in mammalian body and exclusively depends on aerobic energy metabolism using oxygen and glucose. Thus, the oxygen molecule is not only an indispensable material for highly organized CNS activities but also a cytotoxic agent which constantly brings oxidative stresses to neurons during their long life without division. In addition, the brain readily undergoes oxidative damage as a result of cerebrovascular injury such as ischemia and this causes neuronal degeneration and death. Since mature neurons can not regenerate, once the survived neurons degenerate, neuronal activity is irreversibly declined. Thus, elucidation of the protection machinery of neuronal cells against oxidative damage is not only an important clue to understand the mechanism(s) of postmitotic neurons to be long-lived but also should provide useful information to design the cure for a number of neurological pathologies.

Keywords

Nerve Growth Factor Hippocampal Neuron Neuronal Death Oxygen Atmosphere Oxygen Toxicity 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ames, B.N., Shigenaga, M.K. and Hogen, T.M., 1993, Oxidants, antioxidants, and the degenerative diseases of aging, Proc. Natl. Acad. Sci. USA. 90: 7915–7922.PubMedCrossRefGoogle Scholar
  2. Dyrks, T., Dyrks, E., Hartmann, T., Masters, C. and Beyreuther, K., 1992, Amyloidogenicity of ßA4 and ßA4-bearing amyloid protein precursor fragments by metal-catalyzed oxidation, J. Biol. Chem. 267: 18210–18217.PubMedGoogle Scholar
  3. Ellis R.E., Yuan J.Y. and Horvitz H.R., 1991, Mechanisms and functions of cell death, Annu. Rev. Cell Biol. 7: 663–698.PubMedCrossRefGoogle Scholar
  4. Enokido, Y. and Hatanaka, H., 1990, High oxygen atmosphere for neuronal cell culture with nerve growth factor. II. Survival and growth of clonal rat pheochromocytoma PC12h cells, Brain Res. 536: 23–29.PubMedCrossRefGoogle Scholar
  5. Enokido, Y., Akaneya, Y., Niinobe, M., Mikoshiba, K. and Hatanaka, H., 1992, Basic fibroblast growth factor rescues CNS neurons from cell death caused by high oxygen atmosphere, Brain Res. 599: 26 1271.Google Scholar
  6. Enokido, Y. and Hatanaka, H., 1993, Apoptotic cell death occurs in hippocampal neurons cultured in a high oxygen atmosphere, Neuroscience, 57: 965–972.PubMedCrossRefGoogle Scholar
  7. Franklin J.L. and Johnson E.M. Jr., 1992, Suppression of programmed neuronal death by sustained elevation of cytoplasmic calcium, Trends Neurosci. 12: 501–508.CrossRefGoogle Scholar
  8. Jackson, G.R., Apffel, L., Werrbach-Perez, K. and Perez-Polo, J.R., 1990, Role of nerve growth factor inGoogle Scholar
  9. oxidant-antioxidant balance and neural injury. I. Stimulation of hydrogen peroxide resistance., J. Neurosci. Res. 25: 360–368.Google Scholar
  10. Ichikawa, M., Muramoto, K., Kobayashi, K., Kawahara, M. and Kuroda Y., 1993, Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study, Neurosci. Res. 16: 95–103.PubMedCrossRefGoogle Scholar
  11. Lafon-Cazal, M., Pietri, S., Culcasi, M. and Bockaert, J., 1993, NMDA-dependent superoxide production and neurotoxicity, Nature 364: 535–537.PubMedCrossRefGoogle Scholar
  12. Lipton, S.A., Choi, Y.-B., Pan, Z.-H., Lei, S.Z., Chen, H.-S. V., Sucher, N.J., Loscalzo, J., Singel, D.I. and Stamler, J.S., 1993, A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds, Nature 364: 626–632.PubMedCrossRefGoogle Scholar
  13. Oppenheim R. W., 1991, Cell death during development of the nervous system, Annu. Rev. Neurosci. 14: 453–501.PubMedCrossRefGoogle Scholar
  14. Orgel, L.E., 1963, The maintenance of the accuracy of protein synthesis and its relevance to aging, Proc. Natl. Acad. Sci. 49: 517–521.PubMedCrossRefGoogle Scholar
  15. Przedborski, S., Kostic, V., Jackson-Lewis, V., Naini, A.B., Simonetti, S., Fahn, S., Carlson, E., Epstein, C.J. and Cadet, J.L., 1992, Transgenic mice with increased Cu/Zn-Superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity., J. Neurosci. 12: 1658–1667.PubMedGoogle Scholar
  16. Rosen, D.R., Siddique, T., Patterson, D., Figlewicz, D.A., Sapp, P., et al., 1993, Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature 362: 5962.CrossRefGoogle Scholar
  17. Spina, M. B., Squinto, S. P., Miller, J., Lindsay, R. M. and Hyman, C., 1992, Brain-derived neurotrophic factor protects dopaminergic neurons against 6-hydroxydopamine and N-methyl-4-phenyl-pyridinium ion toxicity: involvement of the glutathione system, J. Neurochem. 59: 99–106.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Yasushi Enokido
    • 1
  • Tomoko Yonemasu
    • 1
  • Takekazu Kubo
    • 1
  • Masumi Ichikawa
    • 2
  • Hiroshi Hatanaka
    • 1
  1. 1.Division of Protein BiosynthesisInstitute for Protein Research Osaka UniversityOsaka 565Japan
  2. 2.Departments of Anatomy and EmbryologyTokyo Metropolitan Institute for NeuroscienceTokyo 183Japan

Personalised recommendations