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 (βA25–35 and βA1–40) and generation of hydrogen peroxide on cortical cultured astrocytes. Twenty-four hours after a single addition of either βA25–35 or βA1–40 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 βA25–35 effects were also insensitive to peroxide. Catalase or vitamin E showed no protective effect against βA25–35 toxicity. Dithiothreitol (DTT), N-acetylcysteine (NAC), and cyclosporine A significantly prevented the toxic effects of both βA25–35 and peroxide. Inhibition of peroxide detoxifying enzymes increased βA25–35 and peroxide toxicity. Exposure to βA25–35 or βA1–40 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.

Keywords

• astrocytes
• β-Amyloid
• Alzheimer's disease
• reactive oxygen species