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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.)

Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis

Texto completo
Autor(es):
Moraes, Miriam S. [1] ; Costa, Paulo E. [2] ; Batista, Wagner L. [3, 4] ; Paschoalin, Taysa [3] ; Curcio, Marli F. [2, 3] ; Borges, Roberta E. [2] ; Taha, Murched O. [5] ; Fonseca, Fabio V. [6] ; Stern, Arnold [7, 8] ; Monteiro, Hugo P. [2]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Quim, Dept Biochem, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Ctr Cellular & Mol Therapy CTCMol, Dept Biochem, BR-04044010 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, BR-04044010 Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo - Brazil
[5] Univ Fed Sao Paulo, Dept Surg, BR-04044010 Sao Paulo - Brazil
[6] Case Western Univ, Inst Transformat Mol Med, Dept Med, Cleveland, OH - USA
[7] NYU, Sch Med, Dept Pharmacol, New York, NY - USA
[8] Univ Spiritu Santo Ecuador, Sch Med, Guayaquil - Ecuador
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: Archives of Biochemistry and Biophysics; v. 558, p. 14-27, SEP 15 2014.
Citações Web of Science: 28
Resumo

Nitric oxide (NO) is involved in angiogenesis and stimulates the EGF-R signaling pathway. Stimulation of different endothelial cell lines with bradykinin (BK) activates the endothelial NO synthase (eNOS) and promotes EGF-R tyrosine phosphorylation. Increase in NO production correlated with enhanced phosphorylation of tyrosine residues and S-nitrosylation of the EGF-R. NO-mediated stimulatory effects on tyrosine phosphorylation of the EGF-R, where cGMP independent. Inhibition of soluble guanylyl cyclase followed by BK stimulation of human umbilical vein endothelial cells (HUVECs) did not change tyrosine phosphorylation levels of EGF-R. BK-stimulation of HUVEC promoted S-nitrosylation of the phosphatase SHP-1 and of p21Ras. Phosphorylation and activation of the ERK1/2 MAP kinases mediated by BK was dependent on the activation of the B2 receptor, of the EGF-R, and of p21 Ras. Inhibition of BK-stimulated S-nitrosylation prevented the activation of the ERK1/2 MAP kinases. Furthermore, activated ERK1/2 MAP kinases inhibited internalization of EGF-R by phosphorylating specific Thr residues of its cytoplasmic domain. BK-induced proliferation of endothelial cells was partially inhibited by the NOS inhibitor (L-NAME) and by the MEK inhibitor (PD98059). BK stimulated the expression of vascular endothelial growth factor (VEGF). VEGF expression was dependent on the activation of the EGF-R, the B2 receptor, p21Ras, and on NO generation. A Matrigel (R)-based in vitro assay for angiogenesis showed that BK induced the formation of capillary-like structures in HUVEC, but not in those cells expressing a mutant of the EGF-R lacking tyrosine kinase activity. Additionally, pre-treatment of BK-stimulated HUVEC with L-NAME, PD98059, and with SU5416, a specific inhibitor of VEGFR resulted in inhibition of in vitro angiogenesis. Our findings indicate that BK-mediated angiogenesis in endothelial cells involves the induction of the expression of VEGF associated with the activation of the NO/EGF-R/p21Ras/ERK1/2 MAP kinases signaling pathway. (C) 2014 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 12/10470-1 - O papel do óxido nítrico e da enzima óxido nítrico sintase induzível na progressão de tumores humanos de cólon
Beneficiário:Hugo Pequeno Monteiro
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 07/59617-6 - Estudos da compartimentalização celular da proteína G de baixo peso molecular Ras e da proteína antioxidante tiorredoxina sob estímulo de fontes geradoras de óxido nítrico
Beneficiário:Hugo Pequeno Monteiro
Linha de fomento: Auxílio à Pesquisa - Regular
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