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Maria L. de Ceballos, Begoña Brera, María Paz Fernández-Tomé

?-Amyloid-Induced Cytotoxicity, Peroxide Generation and Blockade of Glutamate Uptake in Cultured Astrocytes

?-Amyloid (?A) is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated ?A-induced cytotoxicity, peroxide generation and glutamate (Glu) uptake in cultured astrocytes. Twenty-four hours after a single addition of either ?A_25–35 or ?A_1–40 there was a concentration-dependentdecrease in viability. Catalase or vitamin E showed no protective effect against ?A_25–35. Dithiothreitol (DTT), N-acetylcysteine (NAC) and cyclosporine A significantly prevented the toxic effects of both ?A_25–35 and peroxide, while inhibition of peroxide detoxifying enzymes enhanced toxicity. Exposure to ?A_25–35 or ?A_1–40 increased peroxides at 2 h and 24 h, which was prevented by DTT and NAC, but not vitamin E. ?A_25–35 inhibited Glu uptake in astrocytes and neurons in culture. Following exposure of neurons to ?A for 24 h there was decreased uptake and increased Glu levels in the culture medium, that resulted in gradual excitotoxicity.

Clinical Chemical Laboratory Medicine, Walter de Gruyter

Print ISSN: 1434-6621
Volume: 39, 04/2001
Pages: 317 - 318

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