Dehydromonocrotaline induces cyclosporine A-insensitive mitochondrial permeability transition/cytochrome c release

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorSantos, Aline Buda dos
dc.creatorDorta, Daniel Junqueira
dc.creatorPestana, Cezar Rangel
dc.creatorMaioli, Marcos Antonio
dc.creatorCurti, Carlos
dc.creatorMingatto, Fábio Erminio
dc.date2014-05-20T15:32:06Z
dc.date2016-10-25T18:08:12Z
dc.date2014-05-20T15:32:06Z
dc.date2016-10-25T18:08:12Z
dc.date2009-07-01
dc.date.accessioned2017-04-06T00:25:52Z
dc.date.available2017-04-06T00:25:52Z
dc.identifierToxicon. Oxford: Pergamon-Elsevier B.V. Ltd, v. 54, n. 1, p. 16-22, 2009.
dc.identifier0041-0101
dc.identifierhttp://hdl.handle.net/11449/41086
dc.identifierhttp://acervodigital.unesp.br/handle/11449/41086
dc.identifier10.1016/j.toxicon.2009.03.004
dc.identifierWOS:000267011600003
dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2009.03.004
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/883810
dc.descriptionMonocrotaline (MCT) is a pyrrolizidine alkaloid present in plants of the genus Crotalaria that causes cytotoxicity and genotoxicity in animals and humans. It is well established that the toxicity of MCT results from its hepatic bioactivation to dehydromonocrotaline (DHM), an alkylating agent, but the exact mechanism of action remains unknown. In a previous study, we demonstrated DHM's inhibition of mitochondrial NADH-dehydrogenase activity at micromolar concentrations, which is an effect associated with a significant reduction in ATP synthesis. As a follow-up study, we have evaluated the ability of DHM to induce mitochondrial permeability transition (MPT) and its associated processes in isolated rat liver mitochondria. In the presence of 10 mu M Ca(2+), DHM (50-250 mu M) elicited MPT in a concentration-dependent, but cyclosporine A-independent manner, as assessed by mitochondrial swelling, which is associated with mitochondrial Ca(2+) efflux and cytochrome c release. DHM (50-250 mu M) did not cause hydrogen peroxide accumulation but did deplete endogenous glutathione and NAD(P)H, while oxidizing protein thiol groups. These results potentially indicate the involvement of mitochondria, via apoptosis, in the well-documented cytotoxicity of monocrotaline. (C) 2009 Elsevier Ltd. All rights reserved.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherPergamon-Elsevier B.V. Ltd
dc.relationToxicon
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectDehydromonocrotaline
dc.subjectProtein thiol oxidation
dc.subjectMitochondrial permeability transition
dc.subjectCytochrome c
dc.subjectApoptosis
dc.titleDehydromonocrotaline induces cyclosporine A-insensitive mitochondrial permeability transition/cytochrome c release
dc.typeOtro


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