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  • Title: Aldose reductase regulates TNF-alpha-induced cell signaling and apoptosis in vascular endothelial cells.
    Author: Ramana KV, Bhatnagar A, Srivastava SK.
    Journal: FEBS Lett; 2004 Jul 16; 570(1-3):189-94. PubMed ID: 15251463.
    Abstract:
    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.
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