The effect of hypoxia-inducible factor 1-alpha on hypoxia-induced apoptosis in primary neonatal rat ventricular myocytes

AIM: To study the role of hypoxia-inducible factor 1-alpha (HIF-1α) on hypoxia-induced apoptosis in primary neonatal rat ventricular myocytes. METHODS: Primary neonatal rat ventricular myocytes were exposed to hypoxia for 24 hours. HIF-1α activity was suppressed by treating the cells with 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1). The degree of cell apoptosis was assessed by Hoechst 33258 DNA staining. The levels of HIF-1α and the pro-apoptotic proteins Bnip3, Bax and Bad were measured with western blotting. RESULTS: On exposure to hypoxia, there was an increase in the expression levels of HIF-1α, and the pro-apoptotic protein Bnip3 was upregulated. Suppression of HIF-1α activity by YC-1 treatment was followed by blockade of hypoxia-induced apoptosis and Bnip3 expression; however, the changes in the levels of Bax and Bad expression were unclear. CONCLUSION: Acute hypoxia enhanced primary neonatal rat ventricular myocyte apoptosis through the activation of HIF-1α and a mechanism that perhaps involved Bnip3. Targeting HIF-1α may be a new strategy for reducing the degree of hypoxia-induced apoptosis in ventricular myocytes.