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

Abstract β-Amyloid is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated the cytotoxicty of β-amyloid peptides (βA 25–35 and βA 1–40 ) and generation of hydrogen peroxide on cortical cultured astrocytes. Twenty-four hours after a single addition of either βA 25–35 or βA 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 βA 25–35 effects were also insensitive to peroxide. Catalase or vitamin E showed no protective effect against βA 25–35 toxicity. Dithiothreitol (DTT), N -acetylcysteine (NAC), and cyclosporine A significantly prevented the toxic effects of both βA 25–35 and peroxide. Inhibition of peroxide detoxifying enzymes increased βA 25–35 and peroxide toxicity. Exposure to βA 25–35 or βA 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 βA toxicity, these results suggest that βA-induced cytotoxicity to astrocytes in culture is, as in neurons, mediated by generation of hydrogen peroxide.