Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/198711
Type: Artigo de periódico
Title: Mitochondria Generated Nitric Oxide Protects Against Permeability Transition Via Formation Of Membrane Protein S-nitrosothiols.
Author: Leite, Ana Catarina R
Oliveira, Helena C F
Utino, Fabiane L
Garcia, Rafael
Alberici, Luciane C
Fernandes, Mariana P
Castilho, Roger F
Vercesi, Aníbal E
Abstract: Mitochondria generated nitric oxide (NO) regulates several cell functions including energy metabolism, cell cycling, and cell death. Here we report that the NO synthase inhibitors (L-NAME, L-NNA and L-NMMA) administered either in vitro or in vivo induce Ca2+-dependent mitochondrial permeability transition (MPT) in rat liver mitochondria via a mechanism independent on changes in the energy state of the organelle. MPT was determined by the occurrence of cyclosporin A sensitive mitochondrial membrane potential disruption followed by mitochondrial swelling and Ca2+ release. In in vitro experiments, the effect of NOS inhibitors was dose-dependent (1 to 50 microM). In addition to cyclosporin A, L-NAME-induced MPT was sensitive to Mg2+ plus ATP, EGTA, and to a lower degree, to catalase and dithiothreitol. In contrast to L-NAME, its isomer D-NAME did not induce MPT. L-NAME-induced MPT was associated with a significant decrease in both the rate of NO generation and the content of mitochondrial S-nitrosothiol. Acute and chronic in vivo treatment with L-NAME also promoted MPT and decreased the content of mitochondrial S-nitrosothiol. SNAP (a NO donor) prevented L-NAME mediated MPT and reversed the decrease in the rate of NO generation and in the content of S-nitrosothiol. We propose that S-nitrosylation of critical membrane protein thiols by NO protects against MPT.
Subject: Animals
Enzyme Inhibitors
Female
In Vitro Techniques
Membrane Potential, Mitochondrial
Mitochondria, Liver
Mitochondrial Membrane Transport Proteins
Mitochondrial Swelling
Ng-nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Donors
Nitric Oxide Synthase
Rats
Rats, Wistar
S-nitroso-n-acetylpenicillamine
S-nitrosothiols
Rights: fechado
Identifier DOI: 10.1016/j.bbabio.2010.01.034
Address: http://www.ncbi.nlm.nih.gov/pubmed/20138021
Date Issue: -1-Uns- -1
Appears in Collections:Unicamp - Artigos e Outros Documentos

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