Upregulation of heme oxygenase-1 expression by curcumin conferring protection from hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblasts

BACKGROUND: Curcumin is a major constituent of rhizomes of Curcuma longa that elicits beneficial effects for oxidative damage. The aim of this study was to investigate whether curcumin could attenuate hydrogen peroxide (H(2)O(2))-induced apoptosis in H9c2 cardiomyoblasts and the underlying mechanisms. RESULTS: The present study showed that exposure of H9c2 cells to H(2)O(2) caused a significant increase in apoptosis as evaluated by flow cytometry analysis and the pretreatment of curcumin protected against H(2)O(2)-induced apoptosis. Exposure of cells with curcumin caused a dose-dependent induction of heme oxygenase-1 (HO-1) protein expression. Curcumin also decreased the cleaved caspase-3 (CC3) protein expression level and increased the Bcl-2/Bax ratio in H(2)O(2)-stimulated H9c2 cells. ZnPP-IX, a HO-1 inhibitor, partly reversed the anti-apoptotic effect of curcumin. Further, LY294002, an inhibitor of PI3K, partially reversed the effect of curcumin on HO-1 protein induction, leading to the attenuation of curcumin-mediated apoptosis resistance. CONCLUSION: These results demonstrated that the anti-apoptotic function of curcumin required the upregulation of HO-1 protein through the PI3K/Akt signaling pathway. Curcumin might be used as a preventive and therapeutic agent for treatment of cardiovascular diseases associated with oxidative stress.