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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
Arai, Roberto J. [1] ; Ogata, Fernando T. [1] ; Batista, Wagner L. [1] ; Masutani, Hiroshi [2] ; Yodoi, Junji [2] ; Debbas, Victor [1] ; Augusto, Ohara [3] ; Stern, Arnold [4] ; Monteiro, Hugo P. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biochem Mol Biol, CINTERGEN, Escola Paulista Med, BR-04044020 Sao Paulo - Brazil
[2] Kyoto Univ, Inst Virus Res, Dept Biol Responses, Kyoto 606 - Japan
[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo - Brazil
[4] NYU, Dept Pharmacol, New York, NY 10003 - USA
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Toxicology and Applied Pharmacology; v. 233, n. 2, p. 227-237, DEC 1 2008.
Citações Web of Science: 23
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. (AU)

Processo FAPESP: 02/10192-0 - Estudo do envolvimento da proteína tiorredoxina no mecanismo de S-nitrosação e seu papel regulador durante a morte celular induzida por óxido nítrico
Beneficiário:Roberto Jun Arai
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 00/12154-2 - Fisiologia molecular da sinalização redox no sistema vascular e modelos de células em cultura
Beneficiário:Francisco Rafael Martins Laurindo
Linha de fomento: Auxílio à Pesquisa - Temático