Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells

被引：36

作者：

Ramana, KV

Bhatnagar, A

Srivastava, SK

机构：

[1] Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA

[2] Univ Louisville, Inst Mol Cardiol, Dept Med, Louisville, KY 40202 USA

来源：

FEBS LETTERS | 2004年 / 570卷 / 1-3期

关键词：

aldose reductase; apoptosis; TNF-alpha; Bcl-2; AP-1; endothelial cell;

D O I：

10.1016/j.febslet.2004.06.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this study, we examined the role of aldose reductase (AR) in regulating the cytotoxic effects of TNF-alpha on human umbilical vein endothelial cells. Inhibition of AR by sorbinil or tolrestat prevented TNF-alpha-induced increase in Bax and Bak and the downregulation of Bcl-2. Inhibition of AR abrogated AP-1 DNA binding activity and prevented the activation of caspase-3, JNK, and p38 MAPK in cells stimulated by TNF-alpha. Exposure to TNF-alpha also induced apoptotic cell death, which was attenuated by AR inhibition or antisense ablation. These observations suggest that AR is a critical regulator of TNF-alpha-induced apoptotic signaling in endothelial cells. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：189 / 194

页数：6

共 22 条

[1] ALDOSE REDUCTASE - CONGENIAL AND INJURIOUS PROFILES OF AN ENIGMATIC ENZYME [J].