title: beta-amyloid peptides are cytotoxic to astrocytes in culture: a role for oxidative stress.
abstract: 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 (betaA(25-35) and betaA(1-40)) and generation of hydrogen peroxide on cortical cultured astrocytes. Twenty-four hours after a single addition of either betaA(25-35) or betaA(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 betaA(25-35) effects were also insensitive to peroxide. Catalase or vitamin E showed no protective effect against betaA(25-35) toxicity. Dithiothreitol (DTT), N-acetylcysteine (NAC), and cyclosporine A significantly prevented the toxic effects of both betaA(25-35) and peroxide. Inhibition of peroxide detoxifying enzymes increased betaA(25-35) and peroxide toxicity. Exposure to betaA(25-35) or betaA(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 betaA toxicity, these results suggest that betaA-induced cytotoxicity to astrocytes in culture is, as in neurons, mediated by generation of hydrogen peroxide.
authors.affiliation: Neurodegeneration Group, Cajal Institute, CSIC, Doctor Arce, 37, Madrid, 28002, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Brera
authors.forename: A
authors.initials: A
authors.lastname: Serrano
authors.forename: M L
authors.initials: ML
authors.lastname: de Ceballos
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)