Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants.
Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta) aggregates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. It was shown that A beta peptides (A beta25-35 and A beta1-40) induce a concentration-dependent accumulation of reactive oxygen species (ROS), decrease the cellular redox activity, and lead to the depletion of ATP levels. The observed inhibition by A beta of mitochondrial function and of glycolysis is blocked by the antioxidants vitamin E, idebenone, and GSH ethyl ester. Taken together, these data suggest that exposure of PC12 cells to A beta results in an impairment of energy metabolism, leading to a deficit in ATP levels and to the compromise of cellular viability. Furthermore, the generation of ROS seems to be a crucial event responsible for the energetic metabolic dysfunction induced by A beta.
Faculty of Medicine, University of Coimbra, Portugal.
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Pereira
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Santos
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Oliveira
D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000502:physiology; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006019:Glycolysis / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014316:Tritium; D014451:Ubiquinone / Q000031:analogs & derivatives; D014810:Vitamin E / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016227:Benzoquinones; D009097:Multienzyme Complexes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D014316:Tritium; D014451:Ubiquinone; D014810:Vitamin E; C077304:glutathione glycylethyl ester; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D005978:Glutathione; C036619:idebenone