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

Publisher Website
Google Scholar
Abstract
In this study, we examined the role of aldose reductase (AR) in regulating the cytotoxic effects of TNF‐α on human umbilical vein endothelial cells. Inhibition of AR by sorbinil or tolrestat prevented TNF‐α‐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‐α. Exposure to TNF‐α 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‐α‐induced apoptotic signaling in endothelial cells.