Thioredoxin-1 promotes survival in cells exposed to S-nitrosoglutathione: Correlation with reduction of intracellular levels of nitrosothiols and up-regulation of the ERK1/2 MAP Kinases

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dc.contributor.authorArai, Roberto J. [UNIFESP]
dc.contributor.authorOgata, Fernando T. [UNIFESP]
dc.contributor.authorBatista, Wagner L. [UNIFESP]
dc.contributor.authorMasutani, Hiroshi
dc.contributor.authorYodoi, Junji
dc.contributor.authorDebbas, Victor [UNIFESP]
dc.contributor.authorAugusto, Ohara
dc.contributor.authorStern, Arnold
dc.contributor.authorMonteiro, Hugo P. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionKyoto Univ
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionNYU
dc.date.accessioned2016-01-24T13:51:57Z
dc.date.available2016-01-24T13:51:57Z
dc.date.issued2008-12-01
dc.description.abstractAccumulating evidence indicates that post-translational protein modifications by nitric oxide and its derived species are critical effectors of redox signaling in cells. These protein modifications are most likely controlled by intracellular reductants. Among them, the importance of the 12 kDa dithiol protein thioredoxin-1 (TRX-1) has been increasingly recognized. However, the effects of TRX-1 in cells exposed to exogenous nitrosothiols remain little understood. We investigated the levels of intracellular nitrosothiols and survival signaling in HeLa cells over-expressing TRX-1 and exposed to S-nitrosoglutahione (GSNO). A role for TRX-1 expression on GSNO catabolism and cell viability was demonstrated by the concentration-dependent effects of GSNO on decreasing TRX-1 expression, activation of capase-3, and increasing cell death. the over-expressaion of TRX-1 in HeLa cells partially attenuated caspase-3 activation and enhanced cell viability upon GSNO treatment. This was correlated with reduction of intracellular levels of nitrosothiols and increasing levels of nitrite and nitrotyrosine. the involvement of ERK, p38 and JNK pathways were investigated in parental cells treated with GSNO. Activation of ERK1/2 MAP kinases was shown to be critical for survival signaling. lit cells over-expressing TRX-1, basal phosphorylation levels of ERK1/2 MAP kinases were higher and further increased after GSNO treatment. These results indicate that the enhanced cell viability promoted by TRX-1 correlates with its capacity to regulate the levels of intracellular nitiosothiols and to up-regulate the survival signaling pathway mediated by the ERK1/2 MAP kinases.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biochem Mol Biol, CINTERGEN, Escola Paulista Med, BR-04044020 São Paulo, Brazil
dc.description.affiliationKyoto Univ, Inst Virus Res, Dept Biol Responses, Kyoto 606, Japan
dc.description.affiliationUniv São Paulo, Inst Quim, Dept Bioquim, BR-01498 São Paulo, Brazil
dc.description.affiliationNYU, Dept Pharmacol, New York, NY 10003 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biochem Mol Biol, CINTERGEN, Escola Paulista Med, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 00/12154-2
dc.description.sponsorshipIDFAPESP: 02/10192-0
dc.description.sponsorshipIDCNPq: 420011/2005
dc.format.extent227-237
dc.identifierhttp://dx.doi.org/10.1016/j.taap.2008.07.023
dc.identifier.citationToxicology and Applied Pharmacology. San Diego: Academic Press Inc Elsevier Science, v. 233, n. 2, p. 227-237, 2008.
dc.identifier.doi10.1016/j.taap.2008.07.023
dc.identifier.issn0041-008X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31083
dc.identifier.wosWOS:000261477900008
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofToxicology and Applied Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectThioredoxinen
dc.subjectNitrosothiolen
dc.subjectNitric oxideen
dc.subjectNitrotyrosineen
dc.subjectp21Rasen
dc.subjectERK1/2 MAP kinasesen
dc.titleThioredoxin-1 promotes survival in cells exposed to S-nitrosoglutathione: Correlation with reduction of intracellular levels of nitrosothiols and up-regulation of the ERK1/2 MAP Kinasesen
dc.typeinfo:eu-repo/semantics/article
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