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

Kota V. Ramana, Aruni Bhatnagar, Satish K. Srivastava

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalFEBS Letters
Volume570
Issue number1-3
DOIs
StatePublished - Jul 16 2004

Keywords

  • AP-1
  • Aldose reductase
  • Apoptosis
  • Bcl-2
  • Endothelial cell
  • TNF-α

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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