Astrocytes overexpressing Cu,Zn superoxide dismutase have increased resistance to oxidative injury.
Overexpression of Cu,Zn SOD (SOD1) can increase survival of neurons under some pathological conditions. Prior studies have shown, however, that SOD1 overexpression can reduce neuronal survival during exposure to superoxide generators by a mechanism involving excess H(2)O(2) accumulation. Since astrocytes exhibit greater H(2)O(2) catabolism capacity than do neurons, the present study examined the effects of SOD1 overexpression on astrocyte survival under these conditions. Cultures were prepared from transgenic mice that overexpress human SOD1 and from nontransgenic littermate controls. Exposure to xanthine oxidase/hypoxanthine (XO/HPX) or menadione caused dose-dependent astrocyte death. In contrast to prior observations with neurons, astrocytes that overexpress SOD1 showed increased resistance to superoxide toxicity. Surprisingly, increased survival in SOD1 overexpressing cultures remained evident even when H(2)O(2) catabolism was inhibited by preincubation with aminotriazole (to block catalase) and buthionine sulfoximine (to deplete glutathione). These findings suggest differences in superoxide metabolism between neurons and astrocytes, and that the greater resistance of astrocytes to oxidative stress is due at least partly to factors other than greater glutathione peroxidase and catalase activity in astrocytes. GLIA 33:343-347, 2001. Published 2001 Wiley-Liss, Inc.
Department of Neurology, University of California and Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
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Chen
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Chan
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Swanson
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D014812:Vitamin K / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014812:Vitamin K; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase