Small GTP binding protein Ras contributes to norepinephrine-induced mitogenesis of vascular smooth muscle cells.
Prostaglandins Other Lipid Mediat
; 65(1): 33-43, 2001 May.
Article
em En
| MEDLINE
| ID: mdl-11352225
ABSTRACT
Norepinephrine stimulates release of arachidonic acid from tissue lipids. Arachidonic acid metabolites generated through the lipoxygenase and cytochrome P-450 pathways but not cyclooxygenase stimulate mitogen activated protein (MAP) kinase activity and proliferation of vascular smooth muscle cells (VSMC). Moreover, norepinephrine has been shown to activate the Ras/MAP kinase pathway through generation of cytochrome P450 metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE). The purpose of this study was to investigate the contribution of Ras in norepinephrine-induced mitogenesis in aortic VSMC. Farnesylation of Ras by farnesyl transferase is required for its full activation. Norepinephrine-induced DNA synthesis, as measured by [3H]-thymidine incorporation, was attenuated by inhibitors of Ras farnesyl transferase FPT III and BMS-191563. These agents also inhibited 20-HETE-stimulated [3H]-thymidine incorporation. In cells transiently transfected with dominant negative Ras (RasN17), norepinephrine, and 20-HETE-induced proliferation of VSMC was attenuated. Both norepinephrine and 20-HETE increased localization of Ras to plasma membrane and MAP kinase activity; FPT III attenuated these effects. These data suggest that VSMC proliferation induced by norepinephrine and 20-HETE is mediated by Ras/MAP kinase pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Norepinefrina
/
Proteínas ras
/
Mitose
/
Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
Prostaglandins Other Lipid Mediat
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos