- 作者: Hong-Jye Hong; Ju-Chi Liu; Paul Chan; Shu-Hui Juan; Shih-Hurng Loh; Jaung-Geng Lin; Tzu-Hurng Cheng
- 作者服務機構: School of Chinese Medicine, China Medical University, Taichung, Department of Medicine and Clinical Research Center, Taipei Medical University-Wan Fang Hospital, Department of Pharmacology, National Defense Medical Center, Taipei , and Institute of Chinese Medical Science, China Medical University Taichung, Taiwan, ROC
- 中文摘要: --
- 英文摘要: It is well documented that 17[β-estradiol(E2) exerts a car-diovascular protective effect. A possible role of E2 in theregulation of endothelin-1(ET-1)production has beenreported. However, the complex mechanisms by whichE2 inhibits ET-1 expression are not completely under-stood. The aims of this study were to examine whetherE2 may alter angiotensin II (Ang II)-induced cell prolifera-tion and ET-1 gene expression and to identify the puta-tive underlying signaling pathways in rat aortic smoothmuscle celIs. Cultured rat aortic smooth muscle cellswere preincubated with E2, then stimulated with Ang II,and [3H]thymidine incorporation and ET-1 gene expres-sion were examined. The effect of E2 on Ang-II-inducedextracellular signal-regulated kinase(ERK) phosphoryla-tion was tested to elucidate the intracellular mechanismof E2 in proliferation and ET-1 gene expression.Ang IIincreased DNA synthesis which was inhibited with E2(1-100 nM〉E2, but not 17α-estradiol,inhibited the Ang-II-induced ET-1 gene expression as revealed by Northernblotting and promoter activity assay. This effect was pre-vented by coincubation with the estrogen receptor an-tagonist ICI 182,780(1 um. E2 also inhibited Ang-II-increased intracellular reactive oxygen species(ROS)asmeasured by a redox-sensitive fluorescent dye, 2',7'-dichlorofluorescin diacetate, and ERK phosphorylation.Furthermore, E2 and antioxidants, such as N-acetyl cys-teine and diphenylene iodonium, decreased Ang-II-in-duced cell proliferation, ET-1 promoter activity, ET-1mRNA, ERK phosphorylation, and activator protein-1-mediated reporter activity. In summary, our results sug-gest that E2 inhibits Ang-II-induced cell proliferation andET-1 gene expression,partially by interfering with theERK pathway via attenuation of ROS generation. Thus,this study provides important new insight regarding themolecular pathways that may contribute to the proposedbeneficial effects of estrogen on the cardiovascular sys-tem.
- 中文關鍵字: --
- 英文關鍵字: --