20-Hydroxyeicosatetraenoic acid induces apoptosis in neonatal rat cardiomyocytes through mitochondrial-dependent pathways.

摘要: OBJECTIVE 20-Hydroxyeicosatetraenoic acid (20-HETE), a [omega]-hydroxylation product of arachidonic catalyzed by cytochrome P450 4A, may play role in the cardiovascular system. It is well known that [omega]-hydroxylase inhibitors markedly reduced cardiac ischemia reperfusion injury. However, direct effect 20-HETE on cardiomyocytes still poorly investigated. Here, we studied cardiomyocyte apoptosis and apoptosis-associated signaling pathways. METHODS AND RESULTS The was measured fluorescein isothiocyanate conjugated annexin V/propidium iodide double staining cytometry, indicating percentage early apoptotic cells increased from 15.6% +/- 2.6% to 25.5% 2.5% control 20-HETE-treated cells, respectively. mitochondrial membrane potential ([DELTA][PSI]m) detecting ratio JC-1 green/red emission intensity. A significant decrease observed after treatment with for 24 hours comparison group, suggesting disruptive [DELTA][PSI]m. In addition, stimulated caspase-3 activity Bax mRNA expression cardiomyocytes. contrast, Bcl-2 levels were significantly decreased treatment. CONCLUSION These results demonstrate induces activation several intrinsic 20-HETE-induced could contribute [omega]-hydroxylase-dependent injure during ischemia-reperfusion.