Pharmacological attenuation of apoptosis in reoxygenated endothelial cells |
| |
Authors: | Email author" target="_blank">A?E?KabakovEmail author K?R?Budagova Y?V?Malyutina D?S?Latchman P?Csermely |
| |
Institution: | (1) Medical Radiology Research Center, 4 Korolev Street, Obninsk, 249036, Russia;(2) Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom;(3) Department of Medical Chemistry, Semmelweis University, P. O. Box. 260, 1444 Budapest, Hungary |
| |
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 M) 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.Received 12 May 2004; received after revision 7 September 2004; accepted 24 September 2004 |
| |
Keywords: | Apoptosis heat shock protein ischemia reperfusion MAP kinase |
本文献已被 PubMed SpringerLink 等数据库收录! |
|