43 引文 斯高帕斯(Scopus)

摘要

It has been well documented previously that 17β-estradiol (E 2) exerts a protective effect on cardiovascular tissue. The possible role of E 2 in the regulation of endothelin (ET)-1 production has been previously reported, although the complex mechanisms by which E 2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 was able to alter strain-induced ET-1 gene expression and also to identify the putative underlying signaling pathways that exist within endothelial cells. For cultured endothelial cells, E 2 (1-100 nM), but not 17α-estradiol, inhibited the level of strain-induced ET-1 gene expression and also peptide secretion. This inhibitory effect elicited by E 2 was able to be prevented by the coincubation of endothelial cells with the estrogen receptor antagonist ICI-182,780 (1 μM). E 2 also inhibited strain-enhanced NADPH oxidase activity and intracellular reactive oxygen species (ROS) generation as measured by the redox-sensitive fluorescent dye 2′,7′-dichlorofluorescin diacetate and the level of extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, the presence of E 2 and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity. In summary, we demonstrated, for the first time, that E 2 inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via the attenuation of strain-induced ROS generation. Thus this study delivers important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.
原文英語
頁(從 - 到)H1254-H1261
期刊American Journal of Physiology - Heart and Circulatory Physiology
287
發行號3 56-3
DOIs
出版狀態已發佈 - 九月 2004

ASJC Scopus subject areas

  • Physiology

指紋 深入研究「17β-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells」主題。共同形成了獨特的指紋。

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