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Type: Artigo de periódico
Title: Oxidative Stress In Ca(2+)-induced Membrane Permeability Transition In Brain Mitochondria.
Author: Maciel, E N
Vercesi, A E
Castilho, R F
Abstract: Mitochondrial permeability transition (PT) is a non-selective inner membrane permeabilization, typically promoted by the accumulation of excessive quantities of Ca(2+) 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 Ca(2+)-induced brain mitochondrial PT was stimulated by Na(+) (10 mM) and totally prevented by the combination of ADP and cyclosporin A. Removal of Ca(2+) from the mitochondrial suspension by EGTA or inhibition of Ca(2+) uptake by ruthenium red partially reverted the dissipation of the membrane potential associated with PT. Ca(2+)-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 Ca(2+) uptake. Ca(2+)-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 Ca(2+)-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 Ca(2+)-induced oxidative stress in brain mitochondria leading to secondary damage such as lipid peroxidation.
Subject: Animals
Calcium Signaling
Cell Membrane Permeability
Chelating Agents
Egtazic Acid
Fluorescent Dyes
Free Radicals
Lipid Peroxidation
Membrane Potentials
Oxidative Stress
Rats, Wistar
Reactive Oxygen Species
Citation: Journal Of Neurochemistry. v. 79, n. 6, p. 1237-45, 2001-Dec.
Rights: fechado
Date Issue: 2001
Appears in Collections:Unicamp - Artigos e Outros Documentos

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