Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/5792
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dc.contributor.authorCustódio, José B. A.-
dc.contributor.authorCardoso, Carla M. P.-
dc.contributor.authorAlmeida, Leonor M.-
dc.date.accessioned2008-09-26T17:41:50Z-
dc.date.available2008-09-26T17:41:50Z-
dc.date.issued2002en_US
dc.identifier.citationChemico-Biological Interactions. 140:2 (2002) 169-184en_US
dc.identifier.urihttps://hdl.handle.net/10316/5792-
dc.description.abstractEtoposide (VP-16) is known to promote cell apoptosis either in cancer or in normal cells as a side effect. This fact is preceded by the induction of several mitochondrial events, including increase in Bax/Bcl-2 ratio followed by cytochrome c release and consequent activation of caspase-9 and -3, reduction of ATP levels, depolarization of membrane potential ([Delta][Psi]) and rupture of the outer membrane. These events are apoptotic factors essentially associated with the induction of the mitochondrial permeability transition (MPT). VP-16 has been shown to stimulate the Ca2+-dependent MPT induction similarly to prooxidants and to promote apoptosis by oxidative stress mechanisms, which is prevented by glutathione (GSH) and N-acetylcysteine (NAC). Therefore, the aim of this work was to study the effects of antioxidants and thiol protecting agents on MPT promoted by VP-16, attempting to identify the underlying mechanisms on VP-16-induced apoptosis. The increased sensitivity of isolated mitochondria to Ca2+-induced swelling, Ca2+ release, depolarization of [Delta][Psi] and uncoupling of respiration promoted by VP-16, which are prevented by cyclosporine A proving that VP-16 induces the MPT, are also efficiently prevented by ascorbate, the primary reductant of the phenoxyl radicals produced by VP-16. The thiol reagents GSH, dithiothreitol and N-ethylmaleimide, which have been reported to prevent the MPT induction, also protect this event promoted by VP-16. The inhibition of the VP-16-induced MPT by antioxidants agrees with the prevention of etoposide-induced apoptosis by GSH and NAC and suggests the generation of oxidant species as a potential mechanism underlying the MPT that may trigger the release of mitochondrial apoptogenic factors responsible for apoptotic cascade activation.en_US
dc.description.urihttp://www.sciencedirect.com/science/article/B6T56-45MDTK0-1/1/8c058bbb86c4e2aa262e5705ce08671fen_US
dc.format.mimetypeaplication/PDFen
dc.language.isoengeng
dc.rightsopenAccesseng
dc.subjectEtoposideen_US
dc.subjectAnticanceren_US
dc.subjectApoptosisen_US
dc.subjectMitochondrial permeability transitionen_US
dc.subjectAntioxidantsen_US
dc.subjectOxidative stressen_US
dc.titleThiol protecting agents and antioxidants inhibit the mitochondrial permeability transition promoted by etoposide: implications in the prevention of etoposide-induced apoptosisen_US
dc.typearticleen_US
dc.identifier.doi10.1016/S0009-2797(02)00020-0-
item.fulltextCom Texto completo-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypearticle-
item.cerifentitytypePublications-
crisitem.author.orcid0000-0002-7769-4712-
Appears in Collections:FFUC- Artigos em Revistas Internacionais
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