Astrocytes overexpressing Cu,Zn superoxide dismutase have increased resistance to oxidative injury

Overexpression of Cu,Zn SOD (SOD1) can increase survival of neurons under s ome pathological conditions. Prior studies have shown, however, that SOD1 o verexpression can reduce neuronal survival during exposure to superoxide ge nerators by a mechanism involving excess H2O2 accumulation. Since astrocyte s exhibit greater H2O2 catabolism capacity than do neurons, the present stu dy examined the effects of SOD1 overexpression on astrocyte survival under these conditions. Cultures were prepared from transgenic mice that overexpr ess human SOD1 and from nontransgenic littermate controls. Exposure to xant hine oxidase/hypoxanthine (XO/HPX) or menadione caused dose-dependent astro cyte death. In contrast to prior observations with neurons, astrocytes that overexpress SOD1 showed increased resistance to superoxide toxicity. Surpr isingly, increased survival in SOD1 overexpressing cultures remained eviden t even when H2O2 catabolism was inhibited by preincubation with aminotriazo le (to block catalase) and buthionine sulfoximine (to deplete glutathione). These findings suggest differences in superoxide metabolism between neuron s and astrocytes, and that the greater resistance of astrocytes to oxidativ e stress is due at least partly to factors other than greater glutathione p eroxidase and catalase activity in astrocytes. GLIA 33: 343-347, 2001. Publ ished 2001 Wiley-Liss, Inc.(+)