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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.)

Ras, Rac1, and phosphatidylinositol-3-kinase (PI3K) signaling in nitric oxide induced endothelial cell migration

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Autor(es):
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Eller-Borges, Roberta [1] ; Batista, Wagner L. [2] ; da Costa, Paulo E. [1] ; Tokikawa, Rita [1] ; Curcio, Marli F. [1] ; Strumillo, Scheilla T. [1] ; Sartori, Adriano [1] ; Moraes, Miriam S. [1] ; de Oliveira, Graciele A. [1] ; Taha, Murched O. [3] ; Fonseca, Fabio V. [4] ; Stern, Arnold [5, 6] ; Monteiro, Hugo P. [1]
Número total de Autores: 13
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Escola Paulista Med, Ctr Cellular & Mol Therapy CTCMOL, Dept Biochem, BR-04044010 Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Surg, Sao Paulo, SP - Brazil
[4] Case Western Univ, Inst Transformat Mol Med, Dept Med, Cleveland, OH - USA
[5] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY - USA
[6] Univ Espiritu Santo, Escuela Med, Guayaquil - Ecuador
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 47, p. 40-51, MAY 1 2015.
Citações Web of Science: 11
Resumo

The small GTP-binding proteins Ras and Rac1 are molecular switches exchanging GDP for GTP and converting external signals in response to a variety of stimuli. Ras and Rac1 play an important role in cell proliferation, cell differentiation, and cell migration. Rac1 is directly involved in the reorganization and changes in the cytoskeleton during cell motility. Nitric oxide (NO) stimulates the Ras - ERK1/2 MAP kinases signaling pathway and is involved in the interaction between Ras and the phosphatidyl-inositol-3 Kinase (PI3K) signaling pathway and cell migration. This study utilizes bradykinin (BK), which promotes endogenous production of NO, in an investigation of the role of NO in the activation of Rac1 in rabbit aortic endothelial cells (RAEC). NO-derived from BK stimulation of RAEC and incubation of the cells with the s-nitrosothiol S-nitrosoglutathione (GSNO) activated Rac1. NO-derived from BK stimulation promoted RAEC migration over a period of 12 h. The use of RAEC permanently transfected with the dominant negative mutant of Ras (Ras(N17)) or with the non-nitrosatable mutant of Ras (Ras(C118S)); and the use of specific inhibitors of: Ras, PI3K, and Rac1 resulted in inhibition of NO-mediated Rac1 activation. BK-stimulated s-nitrosylation of Ras in RAEC mediates Rac1 activation and cell migration. Inhibition of NO-mediated Rac1 activation resulted in inhibition of endothelial cell migration. In conclusion, the NO indirect activation of Rac1 involves the direct participation of Ras and PI3K in the migration of endothelial cells stimulated with BK. (C) 2015 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 10/19013-7 - Participação da proteína tirosina quinase Src e do óxido nítrico nas vias de sinalização celular estimuladas por estrógeno em linhagens de tumores humanos de mama
Beneficiário:Hugo Pequeno Monteiro
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/52730-7 - Estudo do papel do óxido nítrico na ativação da GTPase RAC-1 e seu envolvimento na manutenção e progressão da metástase tumoral em modelo de melanoma murino
Beneficiário:Hugo Pequeno Monteiro
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 11/14392-2 - Avaliação do envolvimento da GTPase Ras de Paracoccidioides brasiliensis no termo-dimorfismo do fungo e durante o estresse oxidativo e nitrosativo
Beneficiário:Wagner Luiz Batista
Linha de fomento: Auxílio à Pesquisa - Regular