Role of reactive oxygen species-sensitive extracellular signal-regulated kinase pathway in angiotensin II-induced endothelin-1 gene expression in vascular endothelial cells.

摘要: Background: Circulating angiotensin II (Ang II) increases vascular endothelin-1 (ET-1) tissue levels, which in turn mediate a major part of Ang II-stimulated growth and hypertension vivo. also stimulates the generation reactive oxygen species (ROS) within endothelial cells. However, whether ROS are involved II-induced ET-1 gene expression, related intracellular mechanisms occurring cells remain unclear. Methods: Cultured were stimulated with II, thus elicited expression was examined by Northern blotting promoter activity assay. Antioxidant pretreatment performed prior to extracellular signal-regulated kinase (ERK) phosphorylation order elucidate redox-sensitive pathway for expression. Results: The induced inhibited type 1 receptor antagonist (irbesartan). II-enhanced levels irbesartan several antioxidants, antioxidants suppressed Further, II-activated ERK significantly certain antioxidants. An inhibitor, U0126, completely. Cotransfection dominant negative mutant Ras, Raf MEK1 (ERK kinase) attenuated activity, suggesting that Ras/Raf/ERK is required activator protein-1 (AP-1) reporter activities Moreover, mutational analysis showed AP-1 binding site an important cis element Conclusions: Our data suggest ERK-mediated transcriptional plays role