β-amyloid peptides are cytotoxic to astrocytes in culture:: A role for oxidative stress

beta-Amyloid is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated the cytotoxicty of beta-amyloid peptides (beta A(25-35) and beta A(1-40)) and generation of hydrogen peroxide on cortical cultured astrocytes. Twenty-four hours after a single addition of either beta A(25-35) or beta A(1-40) there was a concentration-dependent decrease in viability. This toxicity never exceeded 50% of the population independently of exposure time and concentrations. The subpopulation of astrocytes resistant to beta A(25-35) effects were also insensitive to peroxide. Catalase or vitamin E showed no protective effect against beta A(25-35) toxicity. Dithiothreitol (DTT), N-acetylcysteine (NAC), and cyclosporine A significantly prevented the toxic effects of both beta A(25-35) and peroxide. Inhibition of peroxide detoxifying enzymes increased beta A(25-35) and peroxide toxicity. Exposure to beta A(25-35) or beta A(1-40) increased peroxide production at 2 and 24 h, which was prevented by DTT and NAC, but not vitamin E. Despite the inability of added catalase to reduce beta A toxicity, these results suggest that beta A-induced cytotoxicity to astrocytes in culture is, as in neurons, mediated by generation of hydrogen peroxide. (C) 2000 Academic Press.