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Selective modulation of brain antioxidant defense capacity by genetic or metabolic manipulations

  • Chapter
Oxidative Stress, Cell Activation and Viral Infection

Part of the book series: Molecular and Cell Biology Updates ((MCBU))

Summary

Oxidative stress may play an important role in the pathogenesis of brain injuries associated with aging and neurodegenerative disorders such as Down’s syndrome, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Brain contain several antioxidant enzymes, most importantly, superoxide dismutases (MnSOD and CuZnSOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and catalase. The tripeptide reduced glutathione (GSH) serves as one of the major endogenous antioxidants in protecting mammalian cells against oxidative stress. GSH has a role not only as a substrate for GSH-Px to break down hydrogen peroxide and lipid peroxides but also as free radical scavenger. The individual contribution of these antioxidants in neuronal protection remains unknown and requires elucidation. A first approach to this question was to establish a comprehensive profile of the brain antioxidant defense potential during aging in control mice. A second approach was to use genetic manipulations to construct transgenic mice that overexpress CuZnSOD. These constructed transgenic mice which exhibit increased CuZnSOD activity in the brain would provide a suitable model to further investigate the role of an increased CuZnSOD activity in neuronal aging and Alzheimer-like neuropathology in Down syndrome. A third strategy in assessing the role of a particular antioxidant in brain fonction was to use metabolic manipulations to deplete brain GSH levels with electrophiles that conjugate with GSH in the presence of glutathione S-transferases, such as diethylmaleate (DEM), and to correlate this depletion with brain injury or susceptibility to oxidative stress. Obtention of such a variation of a particular antioxidant in the brain and neurobiological consequences will be evaluated and discussed.

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References

  • Abraham, E.C., Taylor, J.F., Lang, C.A. (1978) Influence of mouse age and erythrocyte age on glutathione metabolism. J. Biochem. 174: 819–825

    CAS  Google Scholar 

  • Anderson, M.E. (1985) Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol. 113: 548–555.

    Article  PubMed  CAS  Google Scholar 

  • Anneren, G. and Epstein, C.J. (1987) Lipid peroxidation and superoxide dismutase-1 and glutathione peroxidase activities in trisomy 16 fetal mice and human trisomy 21 fibroblasts. Pediat. Res. 21: 88–92.

    Article  PubMed  CAS  Google Scholar 

  • Avraham, K.B., Schickler, M., Sapoznikov, D, Yarom, R., Groner, Y. (1988) Down’s syndrome: abnormal neuromuscular junction in tongue of transgenic mice with elevated levels of human CuZn superoxide dismutase. Cell 54: 823–829.

    Article  PubMed  CAS  Google Scholar 

  • Bandy, B. and Davison, A.J. (1990) Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Rad. Biol. Med. 8: 523–539

    Article  PubMed  CAS  Google Scholar 

  • Barja de Quiroga, G., Perez-Campo, R., Lopez-Torrez, M. (1990) Anti-oxidant defenses and peroxidation in liver and brain of aged rats. Biochem J. 272: 247–250.

    Google Scholar 

  • Benzi, G., Pastoris, O., Marzatico, F. and Villa, R.F. (1989a) Age-related effect induced by oxidative stress on the cerebral glutathione system. Neurochem. Res. 14: 473–481.

    Article  PubMed  CAS  Google Scholar 

  • Benzi, G., Marzatico, F., Pastoris, O., Villa, R.F. (1989b) Relationship between aging, drug treatment and the cerebral enzymatic antioxidant system. Exp. Gerontol. 24: 137–148.

    Article  PubMed  CAS  Google Scholar 

  • Berr, C., Nicole, A., Godin, J., Ceballos-Picot, I., Thevenin, M., Dartigues, JF., Alperovitch, A. (1993) Relationships between plasma selenium, erythrocyte selenium, oxygen metabolizing enzyme concentrations and age in elderly community residents: a pilot epidemiologic study. J. Am. Geriatr. Soc. 41: 143–148.

    PubMed  CAS  Google Scholar 

  • Blass, J.P. and Gibson, G.E. (1991) The role of oxidative abnormalities in the pathophysiology of Alzheimer’s disease. Rev. Neurol. 147: 513–525.

    PubMed  CAS  Google Scholar 

  • Bracco, F., Burlina, A.P., Malesani, R., Rigo, A., Battistin, L. (1986) Free-radical related enzymes in the aging brain. In: A. Bès et al. (Eds), Senile dementia, early detection, John Libbey Eurotext, pp. 293–297

    Google Scholar 

  • Brooksbank, B.W.L., Balazs, R. (1984) Superoxide dismutase, glutathione peroxidase and lipoperoxidation in Down syndrome fetal brain. Dey. Brain Res.16: 37–44.

    Google Scholar 

  • Cammer, W., Tansey, F., Abramovitz, M., Ishigaki, S., Listowsky, I. (1989) Differential localization of glutathione-S-transferase Yp and Yb subunits in oligodendrocytes of rat brain. J. Neurochem. 52: 876–883.

    Article  PubMed  CAS  Google Scholar 

  • Cand, F., Verdetti, J. (1989) Superoxide dismutase, glutathione peroxidase, catalase and lipid peroxidation in the major organs of the aging rats. Free Rad. Biol. Med. 7: 59–63.

    Article  PubMed  CAS  Google Scholar 

  • Cao Danh, H., Strolin Benedetti, M., Dostert, P. (1983) Differential changes in superoxide dismutase activity in brain and liver of old rats and mice J. Neurochem.40: 1003–1007.

    Google Scholar 

  • Carney, J.M., Starke-Reed P.E., Oliver, C.N., Landum, R.W., Cheng, M.S., Wu, J.F., Floyd, R.A. (1991) Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin trapping compound N-tert-butyl-a-phenylnitrone. Proc. Natl. Acad. Sci. 88: 3633–3636.

    Article  PubMed  CAS  Google Scholar 

  • Ceballos, I., Delabar, J.M., Nicole, A., Lynch, R.E., Hallewell, R.A., Kamoun, P., Sinet P.M. (1988) Expression of transfected human CuZnSOD in mouse L cells and NS2OY neurobastoma cells induces enhancement of glutathione peroxidase activity. Biochim. Biophys. Acta 949: 58–64.

    PubMed  CAS  Google Scholar 

  • Ceballos, I., Javoy-Agid, F., Hirsch, E.C., Dumas, S., Kamoun, P., Sinet, P.M., Agid, Y. (1989) Localization of copper-zinc superoxide dismutase mRNA in human hippocampus by in situ hybridization. Neurosci. Lett. 105: 41–46.

    Article  PubMed  CAS  Google Scholar 

  • Ceballos, I., Lafon, M., Javoy-Agid, F., Hirsch, E., Nicole, A., Sinet, P.M., Agid, Y. (1990a) Superoxide dismutase and Parkinson’s disease. The Lancet 335: 1035–1036.

    Article  CAS  Google Scholar 

  • Ceballos, I., Javoy-Agid, F., Delacourte, A., Defossez, A., Nicole, A., Sinet, P.M. (1990b) Parkinson’s disease and Alzheimer’s disease: neurodegenerative disorders due to brain antioxidant system deficiency? In: Emerit et al (Eds): Antioxidants in Therapy and Preventive Medicine, Plenum Press, New York, pp. 493–498.

    Chapter  Google Scholar 

  • Ceballos, I., Javoy-Agid, F., Delacourte, A., Defossez, A., Lafon, M., Hirsch, E., Nicole, A., Sinet, P.M., Agid, Y. (1991a) Neuronal localization of copper-zinc superoxide dismutase protein and mRNA within the human hippocampus from control and Alzheimer’s disease brains. Free Rad. Res. Comms. 12–13: 571–580.

    Article  Google Scholar 

  • Ceballos-Picot, I., Nicole, A., Briand, P., Grimber, G., Delacourte, A., Defossez, A., JavoyAgid, F., Lafon, M., Blouin J.L., Sinet, P.M. (1991b) Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice: animal model of gene dosage effect in Down’s syndrome. Brain Res. 552: 198–214.

    Article  PubMed  CAS  Google Scholar 

  • Ceballos, I., Nicole, A., Briand, P., Grimber, G., Delacourte, A., Flament, S., Thevenin, J.M., Kamoun, P., Sinet, P.M. (1991c) Expression of human CuZn superoxide dismutase gene in transgenic mice: model for gene dosage effect in Down’s syndrome. Free Rad. Res. Comms. 12–13: 581–589.

    Article  Google Scholar 

  • Ceballos-Picot, I., Nicole, A., Sinet,PM. (1992a) Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase: model for the study of free radicals metabolism and aging. Free Radicals and Aging.In: Emerit I., Chance B.(Eds) Birkhaüser Verlag, pp. 89–98.

    Google Scholar 

  • Ceballos-Picot, I., Nicole, A., Sinet, P.M. (1992b) Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase. Mut. Res. 275: 281–293.

    CAS  Google Scholar 

  • Ceballos-Picot, I., Trivier, J.M., Nicole, A., Sinet, P.M. and Thevenin, M. (1992c) Age-correlated modifications of copper-zinc superoxide dismutase and glutathione-related enzyme activities in human erythrocytes. Clin. Chem. 38: 66–70.

    PubMed  CAS  Google Scholar 

  • Chance, B., Sies, H., Boveris, A. (1979) Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59: 527–533.

    PubMed  CAS  Google Scholar 

  • Chen, C.J., Warshaw, J.B., Sanadi, D.R. (1972) Regulation of mitochondrial respiration in senescence. J. Cell Physiol. 80: 141–148.

    Article  PubMed  CAS  Google Scholar 

  • Chen, T.S., Richie, J.P. and Lang, C.A. (1989) The effect of aging on glutathione and cysteine levels in different rgions of the mouse brain. Soc. Biol. Med. 190: 399–402

    CAS  Google Scholar 

  • Connor, J.R., Menzies, S.L., Martin, S.M., Mufson, E.J. (1990) Cellular distribution of Transferrin, Ferritin, and Iron in Normal and Aged Human Brains. J. Neurosci. Res. 27: 595611.

    Google Scholar 

  • Delacourte, A., Defossez, A., Ceballos, I., Nicole, A., Sinet, P.M. (1988) Preferential expression of copper-zinc superoxide dismutase in the vulnerable cortical neurons in Alzheimer’s disease. Neurosci. Lett. 92: 247–253.

    Article  PubMed  CAS  Google Scholar 

  • Di Monte, D.A., Chan, P., Sandy, M.S. (1992) Glutathione in Parkinson’s disease: a link between oxidative stress and mitochondrial damage. Ann. Neurol. 32: S111 - S115.

    Article  PubMed  Google Scholar 

  • Dowson, J.H. (1982) Neuronal Lipofuscin Accumulation in ageing and Alzheimer dementia: a pathogenic mechanism. Brit. J. Psychiat. 140: 142–148.

    Article  PubMed  CAS  Google Scholar 

  • Elroy-Stein, O., Bernstein, Y., Groner, Y. (1986) Overproduction of human CuZn superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation. EMBO J. 5: 615–622.

    PubMed  CAS  Google Scholar 

  • Elroy-Stein, O., Groner, Y. (1988) Impaired neurotransmitter uptake in PC12 cells overexpressing human Cu-Zn superoxide dismutase implications for gene dosage effect in Down’s syndrome. Cell 52: 259–267.

    Article  PubMed  CAS  Google Scholar 

  • Epstein, C.J., Avraham, K.B., Lovett, M., Smith, S., Elroy-Stein, 0., Rotman, G., Bry, C.,Groner Y. (1987) Transgenic mice with increase Cu/Zn-superoxide dismutase activity: animal model of gene dosage effects in Down syndrome. Proc. Natl. Acad. Sci. 84: 8044–8048.

    CAS  Google Scholar 

  • Evans, P.H., Klinowski, J., Yano, E., Urano, N. (1989) Alzheimer’s disease: a pathogenic role for aluminosilicate-induced phagocytic free radicals. Free Rad. Res. Comets, 6: 317–321.

    Article  CAS  Google Scholar 

  • Farooqui, M.Y.H, Day, W.W., Zamorano D.M (1987) Glutathione and lipid peroxidation in the aging rat. Comp. Biochem. Physiol. 88B: 177–180

    CAS  Google Scholar 

  • Freeman, B.A. and Crapo, J.D. (1982) Biology of disease: free radicals and tissue injury. Lab. Invest. 47: 412–427.

    PubMed  CAS  Google Scholar 

  • Fucci, L., Oliver, C.N., Coon, M.J., Stadtman, E.R. (1983) Inactivation of key metabolic enzymes by mixed function oxidation reactions: possible implication in protein turnover and ageing. Proc. Natl. Acad. Sci.80: 1521–1525.

    Google Scholar 

  • Gerard-Monnier, D., Fougeat, S. and Chaudiere, J. (1992) Glutathione and cysteine depletion in rats and mice following acute intoxication with Diethylmaleate. Biochem. Pharmacol., 43: 451–456.

    Article  PubMed  CAS  Google Scholar 

  • Geremia, E., Baratta, D., Zafarana, S., Giordano, R., Pinizotto, M.R., La Rosa, M.G., Garozzo A. (1990) Antioxidant enzymatic systems in neuronal and glial cell-enriched fractions of rat brain during aging. Neurochem. Res. 15: 719–772.

    Article  PubMed  CAS  Google Scholar 

  • Graham, D.G. (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol. Pharmacol. 14: 633–634.

    PubMed  CAS  Google Scholar 

  • Griffith, O., and Meister, A. (1979) Glutathione: interorgan translocation, turnover and metabolism. Proc. Natl. Acad. Sci. 76: 5605–5610

    Google Scholar 

  • Griffith, O. (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal. Biochem. 106: 207–212.

    Article  PubMed  CAS  Google Scholar 

  • Harman, D. (1981) The aging process. Proc. Natl. Acad. Sci. USA 78: 7124–7128.

    Article  PubMed  CAS  Google Scholar 

  • Hazelton, G.A., and Lang C.A. (1980) Glutathione content of tissues in the aging mouse. J. Biochem. 188: 25–30

    CAS  Google Scholar 

  • Hazelton, G.A. and Lang, C.A. (1985) Glutathione peroxidase and reductase activities in the aging mouse. Mech. Ageing Dey. 29: 71–78.

    Article  CAS  Google Scholar 

  • Hothersall, J.S., El-Hassan, A., McLean, P., Greenbaum, A.L. (1981) Age-related changes in enzymes of rat brain. 2. Redox system linked to NADPH and glutathione. Enzyme 26: 271276.

    Google Scholar 

  • Jain, A., Martensson, J., Stole, E., Auld, P.A.M., Meister, A. (1991) Glutathione deficiency leads to mitochondrial damage in brain. Proc. Natl. Acad. Sci., 88: 1913–1917

    Article  PubMed  CAS  Google Scholar 

  • Kellogg, E.W., Fridovich, I. (1976) Superoxide dismutase in the rat and mouse as a function of age and longevity. J. Gerontol. 31: 405–408.

    PubMed  CAS  Google Scholar 

  • Ledig, M., Fried, R., Ziessel, M., Mandel, P. (1982) Regional distribution of superoxide dismutase in rat brain during postnatal development. Dey. Brain Res. 4: 333–337.

    Article  CAS  Google Scholar 

  • Marklund, S.L., Adolfsson, R., Gottfries, C.G., Winblad, B. (1985) Superoxide dismutase isoenzymes in normal brains and in brains from patients whith dementia of Alzheimer type J. Neurol. Sci. 67: 319–325.

    Article  PubMed  CAS  Google Scholar 

  • Martensson, J., Jain, A., Stole, E., Frayer, W., Auld, P.A.M., Meister, A. (1991) Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress. Proc. Natl. Aced. Sci., 88: 9360–9364.

    Article  CAS  Google Scholar 

  • Marttila, R.J., Lorentz, H., Rinne, U.K (1988) Oxygen toxicity protecting enzymes in Parkinson’s disease. Increase of superoxide dismutase-lie activity in the substantia nigra and basal nucleus. J. Neurol. Sci. 86: 321–331.

    Article  PubMed  CAS  Google Scholar 

  • Massie, H.R., Aiello, V.R., Iodice, A.A. (1979) Changes with age in copper and superoxide dismutase levels in brains of C57BL/6J mice. Mech. Ageing Dev.10: 93–99.

    Google Scholar 

  • Meister, A. and Anderson, M.E. (1983) Glutathione. Ann. Rev. Biochem. 52: 711–760

    Article  PubMed  CAS  Google Scholar 

  • Mizuno, Y., Ohta, K. (1986) Regional distribution of thiobarbituric acid-reactive products, activities of enzymes regulating the metabolism of oxygen free radicals and some of the related enzymes in adult and aged rat brain. J. Neurochem. 46: 1344–1352.

    Article  PubMed  CAS  Google Scholar 

  • Naryshkin, S., Miller, L., Lindeman, R. and Lang, C.A. (1981) Blood glutathione: a biochemical index of human aging. Fed. Proc. 40: 3179.

    Google Scholar 

  • Norris, K.H., Hornsby, P.J. (1990) Cytotoxic effects of expression of human superoxide dismutase in bovine adrenocortical cells. Mutation Res. 237: 95–106.

    Article  PubMed  CAS  Google Scholar 

  • Perry, T.L., Godin, D.V., Hansen, S. (1882) Parkinson’s disease: a disorder due to nigral glutathione deficiency. Neurosci. Lett. 33: 305–310.

    Article  Google Scholar 

  • Philbert, M.A., Beiswanger, C.M., Waters, D.K., Reuhl, K.R., Lowdes, H.E. (1991) Cellular and regional distribution of reduced glutathione in the nervous system of the rat: histochemical localization by mercury orange andO-Phtaldialdehyde-induced histofluorescence. Toxicol and Applied Pharmacol. 107: 215–227.

    Article  CAS  Google Scholar 

  • Pileblad, E., and Magnusson, T. (1989) Intracerebroventricular administration of L-buthionine sulfoximine: a method for depleting brain glutathione. J. Neurochem. 53: 1878–1882

    Article  PubMed  CAS  Google Scholar 

  • Przedborski, S., Jockson-Lewis, V., Kostic, V., Carlson, E., Epstein, C.J., Cadet, J.L. (1992) Superoxide dismutase, catalase and glutathione peroxidase activities in copper-zinc superoxide dismutase transgenic mice. J. Neurochem. 58: 1760–1767.

    Article  PubMed  CAS  Google Scholar 

  • Raps, S.P., Lai, J.C.K., Hertz, L., Cooper, A.J.L. (1989) Glutathione is present in high

    Google Scholar 

  • concentration in cultured astrocytes but not in cultured neurons. Brain Res. 493: 498–501

    Google Scholar 

  • Ravindranath, V., Shivakumar, B.R., Anandatheerthavarada, H.K. (1989) Low glutahione levels in brain regions of aged rats. Neurosci. Lett. 101: 187–190.

    Article  PubMed  CAS  Google Scholar 

  • Reiss, U. and Gershon, D. (1976) Comparison of cytoplasmic superoxide dismutase in liver, heart and brain of aging rats and mice. Biochim. Biophys. Res. Commun. 73: 255–262.

    Article  CAS  Google Scholar 

  • Rosen, D.R., Siddique, T., Patterson, D. et al., (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362: 59–62

    Article  PubMed  CAS  Google Scholar 

  • Rumble, B., Tetallack, R., Hilbich, C. (1989) Amyloid A4 protein and its precursor in Down’s syndrome and Alzheimer’s disease. New England J. Med. 22: 1146–1452.

    Google Scholar 

  • Sawada, M., Carlson, J.C. (1987) Changes in superoxide radical and lipid peroxide formation in the brain, heart and liver during the life time of the rat. Mech. Ageing Dev.41: 125–137.

    Google Scholar 

  • Scarpa, M., Rigo, A., Viglino, P., Stevanato, R., Bracco, F., Battistin, L. (1987) Age-dependence of the level of the enzymes involved in the protection against active oxygen species in the rat brain. Proc. Soc. Ex. Med. 185: 129–133.

    CAS  Google Scholar 

  • Schneider, D., Naryshkin, S., Lang, C.A. (1982) Blood glutathione, a biochemical index of aging women. Fed. Proc. 41: 7671

    Google Scholar 

  • Scott, M.D., Meshnick, S.R., Eaton, J.W. (1987) Superoxide dismutase rich bacteria. Paradoxal increase in oxidant toxicity. J. Biol. Chem. 262: 3640–3645.

    PubMed  CAS  Google Scholar 

  • Scott, M.D., Meshnick, S.R., Eaton, J.W. (1989) Superoxide dismutase amplifies organismal sensitivity to ionizing radiation. J. Biol. Chem. 264: 2498–2501.

    PubMed  CAS  Google Scholar 

  • Semsei, I., Govinda, R.,Richardson, A. (1991) Expression of superoxide dismutase and catalase in rat brain as a function of age. Mech. Ageing Dev. 58: 13–19.

    CAS  Google Scholar 

  • Sinet, P.M., Couturier, J., Dutrillaux, A., Jerome, H. (1976) Trisomie 21 et superoxide dismutase-1 (IPO-A). Tentative de localisation sur la sous-bande 21g22.1. Exp. Cell. Res. 97: 47–55

    Article  PubMed  CAS  Google Scholar 

  • Sinet, P.M. (1982) Metabolism of oxygen derivatives in Down’s syndrome. Ann NY. Acad. Sci. 386: 82–94.

    Google Scholar 

  • Sinet, P.M. and Ceballos-Picot, I. (1992) Role of free radicals in Alzheimer’s disease and Down’s syndrome. In: L. Packer, L. Prilipko and Y. Christen (eds.): Free Radicals in the Brain Aging, Neurological and Mental Disorders, Springer-Verlag, Berlin Heidelberg, pp. 91–98.

    Google Scholar 

  • Slivska, A., Mytillineou, C., Cohen, G. (1987) Histochemical evaluation of glutathione in brain. Brain Res., 209: 275–284

    Article  Google Scholar 

  • Slivska, A., Spina, M., Calvin, H., Cohen, G. (1988) Depletion of brain glutathione in preweaning mice by L-buthionine sulfoximine. J. Neurochem. 50: 1391–1393.

    Article  Google Scholar 

  • Smith, C.D., Carney, J.M., Starke-Reed, P.E, Oliver, C.N., Stadtman, E.R, Floyd, R.A., Markesbery, W.R. (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc. Natl. Acad. Sci. 88: 10540–10543.

    Article  PubMed  CAS  Google Scholar 

  • Sohal, R.S., Arnold, L.A., Sohal, B. (1990a) Age-related changes in antioxidant enzymes and prooxidant generation in tissues of the rat with special reference to parameters in two insect species. Free Rad Biol. Med.10: 495–500.

    Google Scholar 

  • Sohal, R.S and Allen, R.G. (1990b) Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis. Experiment. Gerontol. 25: 499–522.

    Article  CAS  Google Scholar 

  • Sohal, R.S. (1991) Hydrogen peroxide production by mitochondria may be a biomarker of aging. Mech. Ageing Dev.60: 189–198.

    Google Scholar 

  • Sommerville, M.J., Percy, M.E., Bergeron, C., Yoong, L.K.K., Grima, E.A. McLachlan, D.R.C. (1991) Localization and quantitation of 68 kda neurofilament and superoxide dismutase-1 mRNA in Alzheimer brain. Molec. Brain Res. 9: 1–8.

    Google Scholar 

  • Svennerholm, L., Bostrom, K., Helander, C.G., Jungbjer, B. (1991) Membrane lipids in the aging human brain. J. Neurochem.56: 2051–2059.

    Google Scholar 

  • Teramoto, S., Fukuchi, Y., Uejima, Y., Ito, H. and Orimo, H. (1992) Age-related changes in GSH content of eyes in mice-a comparison f senescence-accelerated mouse (SAM) and C57BL/J mice. Comp. Biochem. Physiol., 102A: 693–696

    Article  CAS  Google Scholar 

  • Ushikima, K., Miyazaki, H., Morioka, T. (1986) Immunohistochemical localization of glutathione peroxidase in the rat brain. Rescucitation 13: 97–105.

    Article  Google Scholar 

  • Vanella, A., Villa, R.F., Gorini, A., Campisi, A., Giuffrida-Stella, A.M. (1989) Superoxide dismutase and cytochrome oxydase activities in light and heavy synaptic mitochondria from rat cerebral cortex during aging. J. Neurosci. Res. 22: 351–355.

    Article  PubMed  CAS  Google Scholar 

  • Vina, J., Sastre, J., Anton, V., Bruseghini, L., Esteras, A. and Asensi, M. Effect of aging on glutathione metabolism, protection by antioxidants. (1992) In: I. Emerit and Chance B. (eds): Free radicals and Aging, Birhaüser Verlag, pp. 89–98

    Google Scholar 

  • Vitoria, J., Machado, A., Satrustegui, J. (1984) Age-dependent variations in peroxide-utilizing enzymes from rat brain mitochondria and cytoplasm. J. Neurochem. 42: 351–356.

    Google Scholar 

  • Wallace, D.C. (1992) Mitochondrial genetics: a paradigm for aging and degenerative diseases?Science 256: 628–632

    CAS  Google Scholar 

  • Wei Soong, N., Hinton, D.R., Cortopassi, G., Arnheim, N. (1992) Mosaicism for a specificsomatic mitochondrial DNA mutation in adult human brain. Nature Genet. 2: 318–323

    Article  PubMed  CAS  Google Scholar 

  • Wong, G.H.W., and Goeddel, D.V (1988) Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science 242: 941–944

    Article  PubMed  CAS  Google Scholar 

  • Yim, M. B., Chock P. B., Stadtman E.R. (1990) Copper, zinc superoxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide. Proc. Natl. Acad. Sci.87: 5006–5010.

    Google Scholar 

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  1. Laboratoire de Biochimie Génétique, CNRS URA 1335, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France

    M. Merad-Boudia, L. Fideler, A. Nicole, B. Aral, P. M. Sinet, P. Briand & I. Ceballos-Picot

  2. ICGM, 22 rue Méchain, 75014, Paris, France

    P. Briand

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  1. M. Merad-Boudia
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Editors and Affiliations

  1. INSERM U. 294, 16, rue Henri Huchard, F-75018, Paris, France

    C. Pasquier

  2. Dept. SIDA & Rétrovirus, Unité d’Oncologie Virale, 25-28, rue du Dr. Roux, F-75015, Paris, France

    R. Y. Olivier

  3. Institut Gustave Roussy, INSERM U. 140, 39, rue Camille Desmoulins, F-94805, Villejuif Cedex, France

    C. Auclair

  4. Dept. of Molecular and Cell Biology, 251 Life Science Addition, Membrane Bioenergetics Group, 94720, Berkeley, CA, USA

    Lester Packer

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Merad-Boudia, M. et al. (1994). Selective modulation of brain antioxidant defense capacity by genetic or metabolic manipulations. In: Pasquier, C., Olivier, R.Y., Auclair, C., Packer, L. (eds) Oxidative Stress, Cell Activation and Viral Infection. Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7424-3_17

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  • DOI: https://doi.org/10.1007/978-3-0348-7424-3_17

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7426-7

  • Online ISBN: 978-3-0348-7424-3

  • eBook Packages: Springer Book Archive

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