Pharmacological attenuation of apoptosis in reoxygenated endothelial cells

A. E. Kabakov, K. R. Budagova, Y. V. Malyutina, D. S. Latchman, P. Csermely

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

BRX-235 (Iroxanadine), a novel drug developed by Biorex (Hungary), was previously characterized as a vasculoprotector against atherosclerosis, an activator of p38 kinase, and an enhancer of stress-responsive heat shock protein (Hsp) expression. The present data demonstrate that BRX-235 may improve survival of vascular endothelial cells (ECs) following ischemia/ reperfusion stress. ECs cultured from human umbilical veins were exposed to hypoxia/reoxygenation to mimic ischemia/reperfusion. Caspase activation and apoptosis were monitored in the reoxygenated cells. Addition of BRX-235 (0.1-1 μM) to culture medium prior to hypoxia or at start of reoxygenation significantly reduced the caspase-dependent apoptosis. The cytoprotection conferred by the pre-hypoxic drug administration was sensitive to quercetin and seems to be based on enhanced Hsp accumulation in stressed ECs. In the case of post-hypoxic drug administration, the cytoprotection was strongly inhibited by SB202190 and SB203580 and appears to be associated with enhanced p38 kinase activation in reoxygenated ECs.

Original languageEnglish
Pages (from-to)3076-3086
Number of pages11
JournalCellular and Molecular Life Sciences
Volume61
Issue number24
DOIs
Publication statusPublished - Dec 1 2004

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Keywords

  • Apoptosis
  • Heat shock protein
  • Ischemia
  • MAP kinase
  • Reperfusion

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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