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

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 生命科學院 > 生物科技學系暨碩士班 > 期刊論文 > Item 310903500/6241

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/6241

题名:	Role of reactive oxygen species–sensitive extracellular signal–regulated kinase pathway in angiotensin II-induced endothelin-1 gene expression in vascular endothelial cells.
作者:	(Hsu YH);(Chen JJ);(Chang NC);(Chen CH);(Liu JC);(Chen TH);(Jeng CJ);(Chao HH);鄭志鴻(CHENG, TZU-HURNG)*
贡献者:	生命科學院生物科技學系
关键词:	Angiotensin II;Endothelin-1;Reactive oxygen species;Extracellular signal-regulated kinase;Endothelial cells
日期:	2004-01
上传时间:	2009-08-25 14:39:14 (UTC+8)
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 vascular growth and hypertension in vivo. Ang II also stimulates the generation of reactive oxygen species (ROS) within vascular endothelial cells. However, whether ROS are involved in Ang II-induced ET-1 gene expression, and the related intracellular mechanisms occurring within vascular endothelial cells remain unclear. Methods: Cultured endothelial cells were stimulated with Ang II, and the thus elicited ET-1 gene expression was examined by Northern blotting and a promoter activity assay. Antioxidant pretreatment of endothelial cells was performed prior to Ang II-induced extracellular signal-regulated kinase (ERK) phosphorylation in order to elucidate the redox-sensitive pathway for ET-1 gene expression. Results: The ET-1 gene was induced with Ang II, which was inhibited with Ang II type 1 receptor antagonist (irbesartan). Ang II-enhanced intracellular ROS levels were inhibited by irbesartan and several antioxidants, and antioxidants also suppressed Ang II-induced ET-1 gene expression. Further, Ang II-activated ERK phosphorylation was also significantly inhibited by certain antioxidants. An ERK inhibitor, U0126, inhibited Ang II-induced ET-1 expression completely. Cotransfection of the dominant negative mutant of Ras, Raf and MEK1 (ERK kinase) attenuated the Ang II-enhanced ET-1 promoter activity, suggesting that the Ras/Raf/ERK pathway is required for Ang II-induced ET-1 gene expression. Ang II-induced activator protein-1 (AP-1) reporter activities were inhibited by antioxidants. Moreover, mutational analysis of the ET-1 gene promoter showed that the AP-1 binding site was an important cis element in Ang II-induced ET-1 gene expression. Conclusions: Our data suggest that ROS are involved in Ang II-induced ET-1 gene expression within endothelial cells. The redox-sensitive ERK-mediated AP-1 transcriptional pathway plays an important role in Ang II-induced ET-1 gene expression.
關聯:	JOURNAL OF VASCULAR RESEARCH 41(1)64 ~74
显示于类别:	[生物科技學系暨碩士班] 期刊論文

文件中的档案:

档案	大小	格式	浏览次数
	58Kb	Unknown	373	检视/开启

在CMUR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....