beta-Amyloid-induced cytotoxicity, peroxide generation and blockade of glutamate uptake in cultured astrocytes.
beta-Amyloid (betaA) is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated betaA-induced cytotoxicity, peroxide generation and glutamate (Glu) uptake in cultured astrocytes. Twenty-four hours after a single addition of either betaA25-35 or betaA1-40there was a concentration-dependent decrease in viability. Catalase or vitamin E showed no protective effect against betaA25-35 Dithiothreitol (DTT), N-acetylcysteine (NAC) and cyclosporine A significantly prevented the toxic effects of both betaA25-35 and peroxide, while inhibition of peroxide detoxifying enzymes enhanced toxicity. Exposure to betaA25-35 or betaA1-40 increased peroxides at 2 h and 24 h, which was prevented by DTT and NAC, but not vitamin E. betaA25-35 inhibited Glu uptake in astrocytes and neurons in culture. Following exposure of neurons to betaA for 24 h there was decreased uptake and increased Glu levels in the culture medium, that resulted in gradual excitotoxicity.
de Ceballos
M L
ML
Cajal Institute, CSIC, Madrid, Spain. mceballos@cajal.csic.es
Brera
B
B
Fernández-Tomé
M P
MP
D000111:Acetylcysteine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism*; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D010446:Peptide Fragments; D010545:Peroxides; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D014810:Vitamin E; D018698:Glutamic Acid; D002374:Catalase; D004229:Dithiothreitol; D000111:Acetylcysteine