Estrogen decreases TNF-α and oxidized LDL induced apoptosis in endothelial cells

被引:45
作者
Florian, M. [1 ]
Magder, S. [1 ]
机构
[1] McGill Univ Hlth Care, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada
基金
加拿大健康研究院;
关键词
apoptosis; atherosclerosis; endothelial cells; estrogen; oxidized low-density lipoprotein; tumor necrosis factor-alpha;
D O I
10.1016/j.steroids.2007.08.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Apoptosis induced by oxidized low-density lipoproteins (oxLDL) and tumor necrosis factor-alpha (TNF-alpha) is believed to contribute to atherosclerosis and vascular dysfunction. Estrogen treatment reduces apoptosis due to TNF-alpha and we hypothesized that it would also reduce apoptosis due to oxLDL. We also explored the anti-apoptotic mechanisms. We used early passage human umbilical vein endothelial cells (HUVEC) grown in steroid-depleted, red phenol-free medium. Cells were synchronized by starvation for 6 h and then treated with oxLDL (75 mu g/ml) or TNF-alpha (20 ng/ml) in the presence of 17-beta-estradiol (E2) (20 nM). Apoptosis was analyzed by flow cytometry and caspase-3 cleavage. We also assessed expression of Bcl-2 and Bcl-xL and phosphorylation of BAD. At 6 h TNF-alpha induced apoptosis but oxLDL did not; E2 did not affect this TNF-alpha induced apoptosis and there was no change in Bcl-2 or Bcl-xL expression. At 24h both TNF-alpha and oxLDL increased apoptosis and E2 reduced the increase. E2 also increased expression of the anti-apoptotic Bcl-2 and Bcl-xL and increased phosphorylation of proapoptotic BAD which reduces its proapoptotic activity at 1 h. However at 24 h there was also an increase in total BAD so that the proportion of phosphorylation of BAD decreased. oxLDL induced apoptosis occurs later than that of TNF-alpha. E2 decreased this late phase apoptosis and this likely requires the production of anti-apoptotic proteins. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:47 / 58
页数:12
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