Mechanism of tetrahydroxy-1,4-quinone cytotoxicity: Involvement of Ca2+ and H2O2 in the impairment of DNA replication and mitochondrial function

dc.creatordeSouzaPinto, NC
dc.creatorVercesi, AE
dc.creatorHoffmann, ME
dc.date1996
dc.date2014-12-02T16:29:31Z
dc.date2015-11-26T16:39:35Z
dc.date2014-12-02T16:29:31Z
dc.date2015-11-26T16:39:35Z
dc.date.accessioned2018-03-28T23:23:13Z
dc.date.available2018-03-28T23:23:13Z
dc.identifierFree Radical Biology And Medicine. Elsevier Science Inc, v. 20, n. 5, n. 657, n. 666, 1996.
dc.identifier0891-5849
dc.identifierWOS:A1996UD14400004
dc.identifier10.1016/0891-5849(95)02179-5
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/53517
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/53517
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/53517
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1272521
dc.descriptionIn this work we investigated the toxicity of a polyphenolic p-benzoquinone derivative, the tetrahydroxy-1,4-quinone (THQ) toward V79 Chinese hamster fibroblasts and analyzed the role of H2O2 and Ca2+ in that mechanism. The exposure of exponentially growing cultures to THQ, in the presence of 1.0 mM Ca2+, caused a dose-dependent inhibition of cell growth and DNA synthesis. Complete prevention of those effects by catalase indicated that H2O2-induced damages should underlie both toxic processes. Further detection of a rise in the intracellular free Ca2+ concentration ([Ca2+]i) in cells exposed to THQ plus Ca2+, together with the partial protection conferred by the intracellular Ca2+-chelator fura-2 against cell growth inhibition, indicated that a disruption of Ca2+ homeostasis is a determinant event in THQ cytotoxicity. Furthermore, the intracellular accumulation of rhodizonic acid (RDZ), the primary oxidative product of THQ, indicated that THQ, or its corresponding semiquinone form, was entering the cells and undergoing further autoxidation to RDZ. It was also evidenced that mitochondria represent an important target in the development of THQ toxicity, as shown by the disruption of the transmembrane electrical potential (Delta psi) of isolated rat liver mitochondria, as well as by the Ca2+-release by mitochondria of permeabilized V79 cells. We concluded that disruption of Ca2+ homeostasis and generation of H2O2 are critically involved in THQ-induced impairment of DNA replication and mitochondrial functions, leading ultimately to cell growth inhibition.
dc.description20
dc.description5
dc.description657
dc.description666
dc.languageen
dc.publisherElsevier Science Inc
dc.publisherNew York
dc.publisherEUA
dc.relationFree Radical Biology And Medicine
dc.relationFree Radic. Biol. Med.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjecttetrahydroxy-1,4-quinone
dc.subjectcalcium
dc.subjecthydrogen peroxide
dc.subjectmitochondria
dc.subjectDNA synthesis
dc.subjectcytotoxicity
dc.subjectfree radicals
dc.subjectBrain Mitochondria
dc.subjectHydrogen-peroxide
dc.subjectCa-2+ Transport
dc.subjectHepatocytes
dc.subjectOxidation
dc.subjectToxicity
dc.subjectPhosphorylation
dc.subjectCatecholamines
dc.subjectEnhancement
dc.subjectGeneration
dc.titleMechanism of tetrahydroxy-1,4-quinone cytotoxicity: Involvement of Ca2+ and H2O2 in the impairment of DNA replication and mitochondrial function
dc.typeArtículos de revistas


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