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

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

Autor Arai, Roberto J. Autor UNIFESP Google Scholar
Ogata, Fernando T. Autor UNIFESP Google Scholar
Batista, Wagner L. Autor UNIFESP Google Scholar
Masutani, Hiroshi Google Scholar
Yodoi, Junji Google Scholar
Debbas, Victor Autor UNIFESP Google Scholar
Augusto, Ohara Google Scholar
Stern, Arnold Google Scholar
Monteiro, Hugo P. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Kyoto Univ
Universidade de São Paulo (USP)
NYU
Resumo Accumulating 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.
Palavra-chave Thioredoxin
Nitrosothiol
Nitric oxide
Nitrotyrosine
p21Ras
ERK1/2 MAP kinases
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 00/12154-2
FAPESP: 02/10192-0
CNPq: 420011/2005
Data de publicação 2008-12-01
Publicado em Toxicology and Applied Pharmacology. San Diego: Academic Press Inc Elsevier Science, v. 233, n. 2, p. 227-237, 2008.
ISSN 0041-008X (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 227-237
Fonte http://dx.doi.org/10.1016/j.taap.2008.07.023
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000261477900008
Endereço permanente http://repositorio.unifesp.br/handle/11600/31083

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