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Type: Artigo de periódico
Title: Oxidative stress in Ca2+-induced membrane permeability transition in brain mitochondria
Author: Maciel, EN
Vercesi, AE
Castilho, RF
Abstract: Mitochondrial permeability transition (PT) is a non-selective inner membrane permeabilization, typically promoted by the accumulation of excessive quantities of Ca2+ ions in the mitochondrial matrix. This phenomenon may contribute to neuronal cell death under some circumstances, such as following brain trauma and hypoglycemia. In this report, we show that Ca2+-induced brain mitochondrial PT was stimulated by Na+ (10 mm) and totally prevented by the combination of ADP and cyclosporin A. Removal of Ca2+ from the mitochondrial suspension by EGTA or inhibition of Ca2+ uptake by ruthenium red partially reverted the dissipation of the membrane potential associated with PT. Ca2+-induced brain mitochondrial PT was significantly inhibited by the antioxidant catalase, indicating the participation of reactive oxygen species in this process. An increased detection of reactive oxygen species, measured through dichlorodihydrofluorescein oxidation, was observed after mitochondrial Ca2+ uptake. Ca2+-induced dichlorodihydrofluorescein oxidation was enhanced by Na+ and prevented by ADP and cyclosporin A, indicating that PT enhances mitochondrial oxidative stress. This could be at least in part a consequence of the extensive depletion in NAD(P)H that accompanied this Ca2+-induced mitochondrial PT. NADPH is known to maintain the antioxidant function of the glutathione reductase/peroxidase and thioredoxin reductase/peroxidase systems. In addition, the occurrence of mitochondrial PT was associated with membrane lipid peroxidation. We conclude that PT further increases Ca2+-induced oxidative stress in brain mitochondria leading to secondary damage such as lipid peroxidation.
Subject: brain mitochondria
cyclosporin A
free radicals
mitochondrial permeability transition
Country: Inglaterra
Editor: Blackwell Publishing Ltd
Rights: fechado
Identifier DOI: 10.1046/j.1471-4159.2001.00670.x
Date Issue: 2001
Appears in Collections:Unicamp - Artigos e Outros Documentos

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