Phytoestrogen α-zearalanol inhibits homocysteine-induced endothelin-1 expression and oxidative stress in human umbilical vein endothelial cells
- 作者：Jinhong Duan ; Haishan Xu ; Shunling Dai ; Xiaoming Wang ; Yunqing Wu ; Y ; ong Zhang ; Renyu Sun ; Jun Ren
- 关键词：Phytoestrogen ;
//www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-ZAL ; Homocysteine ; Endothelin-1 ; Oxidative stress ; AP-1
- 刊名：Atherosclerosis
- 出版年：2008
- 期刊代码：28_00219150
- 类别：med
- 出版时间：April 2008
- 卷：197
- 期：2
- 页码：549-555
- 文件大小：524 K
摘要
Although estrogen replacement therapy may improve dampened endothelial function in postmenopausal women, the associated risk of breast and ovarian cancer has limited its long-term use. Identifying effective alternative remedy with less carcinogenicity is in serious demand. This study was designed to examine the effect of the phytoestrogen 
-zearalanol (-ZAL) on homocysteine-induced endothelin-1 (ET-1) induction, reactive oxygen species (ROS) production and transcription pathways in human umbilical vein endothelial cells (HUVECs). ROS was measured by DCF fluorescent microscopy. Homocysteine-induced expression of ET-1 mRNA, ERK, pERK and c-jun/AP-1 protein was measured using RT-PCR and Western blot analysis, respectively. ET-1 secretion was determined by the enzymatic immunoassay. Transcriptional factor AP-1 expression in response to -ZAL, homocysteine or both was evaluated by transient transfection assay. Our data revealed that -ZAL ablated homocysteine-elicited ET-1 secretion, upregulated ET-1 mRNA and homocysteine-induced ROS accumulation without any effects by itself. -ZAL also nullified homocysteine-induced increase in c-Jun/AP-1 expression/activity without eliciting any effect by itself. Collectively, our data indicated that -ZAL may antagonize homocysteine-induced ET-1 gene induction, ROS accumulation, activation of ERK signaling pathway and AP-1 transcriptional factor, all of which may contribute to -ZAL-induced beneficial effect on endothelial function.
-zearalanol (-ZAL) on homocysteine-induced endothelin-1 (ET-1) induction, reactive oxygen species (ROS) production and transcription pathways in human umbilical vein endothelial cells (HUVECs). ROS was measured by DCF fluorescent microscopy. Homocysteine-induced expression of ET-1 mRNA, ERK, pERK and c-jun/AP-1 protein was measured using RT-PCR and Western blot analysis, respectively. ET-1 secretion was determined by the enzymatic immunoassay. Transcriptional factor AP-1 expression in response to -ZAL, homocysteine or both was evaluated by transient transfection assay. Our data revealed that -ZAL ablated homocysteine-elicited ET-1 secretion, upregulated ET-1 mRNA and homocysteine-induced ROS accumulation without any effects by itself. -ZAL also nullified homocysteine-induced increase in c-Jun/AP-1 expression/activity without eliciting any effect by itself. Collectively, our data indicated that -ZAL may antagonize homocysteine-induced ET-1 gene induction, ROS accumulation, activation of ERK signaling pathway and AP-1 transcriptional factor, all of which may contribute to -ZAL-induced beneficial effect on endothelial function.