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Type: Artigo de periódico
Title: The Redox State Of Endogenous Pyridine Nucleotides Can Determine Both The Degree Of Mitochondrial Oxidative Stress And The Solute Selectivity Of The Permeability Transition Pore.
Author: Zago, E B
Castilho, R F
Vercesi, A E
Abstract: Acetoacetate, an NADH oxidant, stimulated the ruthenium red-insensitive rat liver mitochondrial Ca(2+) efflux without significant release of state-4 respiration, disruption of membrane potential (Deltapsi) or mitochondrial swelling. This process is compatible with the opening of the currently designated low conductance state of the permeability transition pore (PTP) and, under our experimental conditions, was associated with a partial oxidation of the mitochondrial pyridine nucleotides. In contrast, diamide, a thiol oxidant, induced a fast mitochondrial Ca(2+) efflux associated with a release of state-4 respiration, a disruption of Deltapsi and a large amplitude mitochondrial swelling. This is compatible with the opening of the high conductance state of the PTP and was associated with extensive oxidation of pyridine nucleotides. Interestingly, the addition of carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone to the acetoacetate experiment promoted a fast shift from the low to the high conductance state of the PTP. Both acetoacetate and diamide-induced mitochondrial permeabilization were inhibited by exogenous catalase. We propose that the shift from a low to a high conductance state of the PTP can be promoted by the oxidation of NADPH. This impairs the antioxidant function of the glutathione reductase/peroxidase system, strongly strengthening the state of mitochondrial oxidative stress.
Subject: Acetoacetates
Carbonyl Cyanide P-trifluoromethoxyphenylhydrazone
Cell Respiration
Electric Conductivity
Intracellular Membranes
Ion Channels
Membrane Potentials
Membrane Proteins
Mitochondria, Liver
Mitochondrial Membrane Transport Proteins
Mitochondrial Swelling
Oxidative Stress
Rats, Wistar
Reactive Oxygen Species
Substrate Specificity
Sulfhydryl Reagents
Uncoupling Agents
Citation: Febs Letters. v. 478, n. 1-2, p. 29-33, 2000-Jul.
Rights: fechado
Identifier DOI: 
Date Issue: 2000
Appears in Collections:Unicamp - Artigos e Outros Documentos

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