Mitochondrial function impairment induced by amyloid beta-peptide on PC12 cells.
The aim of the present study was to determine whether amyloid beta-peptide (A beta) induces mitochondrial dysfunction. Mitochondrial function was reported to be affected following A beta exposure, as demonstrated by depolarization of the mitochondrial membrane, decrease of oxygen consumption and by the inhibition of complexes I, III and IV of the mitochondrial respiratory chain. A beta25-35 and A beta1-40 peptides also inhibited MTT reduction in a dose-dependent manner in undifferentiated and differentiated PC12 cells. Several antioxidants prevented this inhibitory response, suggesting that oxidative stress is involved in A beta-induced cytotoxicity. These data suggest that mitochondrial dysfunction contributes to amyloid beta-protein cytotoxicity and may play a major role in the abnormalities of energy metabolism observed in Alzheimer's disease.
Centre for Neuroscience of Coimbra, Faculty of Medicine, University of Coimbra, Portugal.
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Pereira
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Santos
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Oliveira
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016015:Logistic Models; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)