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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.title3-Nitropropionic Acid-Induced Mitochondrial Permeability Transition: Comparative Study of Mitochondria From Different Tissues and Brain Regionspt_BR
dc.contributor.authorMirandola, SRpt_BR
dc.contributor.authorMelo, DRpt_BR
dc.contributor.authorSaito, Apt_BR
dc.contributor.authorCastilho, RFpt_BR
unicamp.authorMirandola, Sandra R. Melo, Daniela R. Saito, Angela Castilho, Roger F. Univ Estadual Campinas, Dept Patol Clin, Fac Ciencias Med, BR-13083970 Campinas, SP, Brazilpt_BR
dc.subjectbrain mitochondriapt_BR
dc.subjectHuntington's diseasept_BR
dc.subject.wosNeuronal Cell-deathpt_BR
dc.subject.wosComplex-ii Inhibitionpt_BR
dc.subject.wosOxidative Stresspt_BR
dc.subject.wosStriatal Degenerationpt_BR
dc.subject.wosDecarboxylase Deficiencypt_BR
dc.subject.wosRedox Statept_BR
dc.description.abstractThe adult rat striatum is particularly vulnerable to systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP), which is known to induce degeneration of the caudate-putamen, as occurs in Huntington's disease. The aim of the present study was to compare the susceptibility of isolated mitochondria from different rat brain regions (striatum, cortex, and cerebellum) as well as from the liver, kidney, and heart to mitochondrial permeability transition (MPT) induced by 3NP and Ca(2+). In the presence of micromolar Ca(2+) concentrations, 3NP induces MPT in a dose-dependent manner, as estimated by mitochondrial swelling and a decrease in the transmembrane electrical potential. A 3NP concentration capable of promoting a 10% inhibition of ADP-stimulated, succinate-supported respiration was sufficient to stimulate Ca(2+)-induced MPT. Brain and heart mitochondria were generally more sensitive to 3NP and Ca(2+)-induced MPT than mitochondria from liver and kidney. In addition, a partial inhibition of mitochondrial respiration by 3NP resulted in more pronounced MPT in striatal mitochondria than in cortical or cerebellar organelles. A similar inhibition of succinate dehydrogenase activity was observed in rat tissue homogenates obtained from various brain regions as well as from liver, kidney, and heart 24 hr after a single i.p. 3NP dose. Mitochondria isolated from forebrains of 3NP-treated rats were also more susceptible to Ca(2+)-induced MPT than those of control rats. We propose that the increased susceptibility of the striatum to 3NP-induced neurodegeneration may be partially explained by its susceptibility to MPT, together with the greater vulnerability of this brain region to glutamate receptor-mediated Ca(2+) influx. (C) 2009 Wiley-Liss,
dc.relation.ispartofJournal Of Neuroscience Researchpt_BR
dc.relation.ispartofabbreviationJ. Neurosci. Res.pt_BR
dc.publisherWiley-lisspt_BR 15pt_BR
dc.identifier.citationJournal Of Neuroscience Research. Wiley-liss, v. 88, n. 3, n. 630, n. 639, 2010.pt_BR
dc.sourceWeb of Sciencept_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
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