Pharmacological attenuation of apoptosis in reoxygenated endothelial cells
Autor: | Y. V. Malyutina, A. E. Kabakov, Peter Csermely, K. R. Budagova, David S. Latchman |
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Rok vydání: | 2004 |
Předmět: |
p38 mitogen-activated protein kinases
HSP27 Heat-Shock Proteins Caspase 3 Apoptosis Pharmacology p38 Mitogen-Activated Protein Kinases Cellular and Molecular Neuroscience Heat Shock Transcription Factors Piperidines Heat shock protein Oxazines medicine Humans Protein Isoforms Molecular Biology Caspase Cells Cultured Heat-Shock Proteins biology Endothelial Cells Cell Biology Hypoxia (medical) Cytoprotection Caspase 9 Cell Hypoxia Neoplasm Proteins DNA-Binding Proteins Enzyme Activation Oxygen Gene Expression Regulation Mitogen-activated protein kinase Caspases Immunology biology.protein Molecular Medicine Quercetin medicine.symptom Oxidation-Reduction Molecular Chaperones Transcription Factors |
Zdroj: | Cellular and molecular life sciences : CMLS. 61(24) |
ISSN: | 1420-682X |
Popis: | 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 microM) 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. |
Databáze: | OpenAIRE |
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