The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione-induced apoptosis

The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione-induced apoptosis

Author Tsujita, Maristela Autor UNIFESP Google Scholar
Batista, Wagner L. Autor UNIFESP Google Scholar
Ogata, Fernando T. Autor UNIFESP Google Scholar
Stern, Arnold Google Scholar
Monteiro, Hugo P. Autor UNIFESP Google Scholar
Arai, Roberto J. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract p21Ras protein plays a critical role in cellular signaling that induces either cell cycle progression or apoptosis. Nitric oxide (NO) has been consistently reported to activate p21Ras through the redox sensitive cysteine residue (118). in this study, we demonstrated that the p21Ras-ERK pathway regulates THP-1 monocyte/macrophage apoptosis induced by S-nitrosoglutathione (SNOG). This was apparent from studies in THP-1 cells expressing NO-insensitive p21Ras (p21Ras(C118S)) where the pro-apoptotic action of SNOG was almost abrogated. Three major MAP kinase pathways (ERK, JNK, and p38) that are downstream to p21Ras were investigated. It was observed that only the activation of ERK1/2 MAP kinases by SNOG in THP-1 cells was attributable to p21Ras. the inhibition of the ERK pathway by PD98059 markedly attenuated apoptosis in SNOG-treated THP-1 cells, but had a marginal effect on SNOG-treated THP-1 cells expressing NO-inserisitive p21Ras. the inhibition of the JNK and p38 pathways by selective inhibitors had no marked effects on the percentage of apoptosis. the induction of p21Waf1 expression by SNOG was observed in THP-1 cells harboring mutant and wild-type p21Ras, however in cells expressing mutant Ras, the expression of p21Waf1 was significantly attenuated. the treatment of THP-1 cells expressing wild-type p21Ras with PD98059 resulted in significant attenuation of p21Waf1 expression. These results indicate that the redox sensitive p21Ras-ERK pathway plays a critical role in sensing and delivering the pro-apoptotic signaling mediated by SNOG. (C) 2008 Elsevier Inc. All rights reserved.
Keywords p21Ras
Language English
Date 2008-05-16
Published in Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc Elsevier Science, v. 369, n. 4, p. 1001-1006, 2008.
ISSN 0006-291X (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1001-1006
Access rights Closed access
Type Article
Web of Science ID WOS:000254864700003

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