Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis
| Autor: | Arnold Stern, Taysa Paschoalin, Marli F. Curcio, Wagner L. Batista, Fabio V. Fonseca, Roberta Eller Borges, Paulo E da Costa, Miriam S. Moraes, Murched Omar Taha, Hugo P. Monteiro |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Angiogenesis
Biophysics Neovascularization Physiologic Bradykinin Nitric Oxide Biochemistry Receptor tyrosine kinase Proto-Oncogene Proteins p21(ras) chemistry.chemical_compound Human Umbilical Vein Endothelial Cells Animals Humans Phosphorylation Molecular Biology Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 S-Nitrosothiols Neovascularization Pathologic biology Protein Tyrosine Phosphatase Non-Receptor Type 6 Tyrosine phosphorylation Cell biology ErbB Receptors Vascular endothelial growth factor Gene Expression Regulation chemistry Cancer research biology.protein Tyrosine Angiogenesis Inducing Agents Rabbits Signal transduction Soluble guanylyl cyclase Tyrosine kinase Signal Transduction |
| Zdroj: | Archives of Biochemistry and Biophysics. 558:14-27 |
| ISSN: | 0003-9861 |
| Popis: | 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®-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect