Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/80659
Type: Artigo de periódico
Title: Inhibitory Effects of Adenine Nucleotides on Brain Mitochondrial Permeability Transition
Author: Saito, A
Castilho, RF
Abstract: The adenine nucleotides ADP and ATP are probably the most important endogenous inhibitors of the mitochondrial permeability transition (MPT). We studied the inhibitory effects of adenine nucleotides on brain MPT by measuring mitochondrial swelling and Ca(2+) and cytochrome c release. We observed that in the presence of either ADP or ATP, at 250 mu M, brain mitochondria accumulated more than 1 mu mol Ca(2+) x mg protein(-1). ADP or ATP also prevented Ca(2+)-induced mitochondrial swelling and cytochrome c release. Interestingly, ATP lost most of its inhibitory effects on MPT when the experiments were carried out in the presence of ATP-regenerating systems. These results indicate that MPT inhibition observed in the presence of added ATP could be mainly due to hydrolysis of ATP to ADP. From mitochondrial swelling measurements, half-maximal inhibitory values (K (i)) of 4.5 and 98 mu M were obtained for ADP and ATP, respectively. In addition, a delayed mitochondrial swelling sensitive to higher ADP concentrations was observed. Mitochondrial anoxia/reoxygenation did not interfere with the inhibitory effect of ADP on Ca(2+)-induced MPT, but oxidative phosphorylation markedly decreased this effect. We conclude that ADP is a potent inhibitor of brain MPT whereas ATP is a weaker inhibitor of this phenomenon. Our results suggest that ADP can have an important protective role against MPT-mediated tissue damage under conditions of brain ischemia and hypoglycemia.
Subject: Apoptosis
Brain ischemia
Cell death
Intracellular calcium homeostasis
Mitochondrial permeability transition
Neurodegeneration
Country: EUA
Editor: Springer/plenum Publishers
Rights: fechado
Identifier DOI: 10.1007/s11064-010-0228-x
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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