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

Abstract

BackgroundCurcumin 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 (H2O2)-induced apoptosis in H9c2 cardiomyoblasts and the underlying mechanisms.ResultsThe present study showed that exposure of H9c2 cells to H2O2 caused a significant increase in apoptosis as evaluated by flow cytometry analysis and the pretreatment of curcumin protected against H2O2-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 H2O2-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.ConclusionThese 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.

Partial Inhibition of HO‐1 Attenuates HMP‐Induced Hepatic Regeneration against Liver Injury in Rats

“…No significant differences were found in the percentage of the TUNEL(+) hepatocytes among all groups in vivo and in vitro (Figures 5(a) and 5(b) ). Similarly, the same trend was observed in the mRNA levels of caspase3 and the bcl2/bax ratio, which are indicators of cell apoptosis related to HO-1 [ 14 ] (Figures 5(c) and 5(d) ).…”

“…HO-1 exerts significant beneficial effects on the maintenance of primary liver function due to potent antiapoptotic and proproliferative properties [ 7 , 19 ]. Previous studies have provided evidence that the antiapoptotic and proproliferative effects of HO-1 involve an increased Bcl-2/Bax ratio and decreased caspase 3 [ 14 ] and p27-cell cycle inhibitor expression [ 20 ], respectively. Therefore, we speculate that the HO-1 expression level may be related to these effects.…”

Naturally Derived Heme-Oxygenase 1 Inducers and Their Therapeutic Application to Immune-Mediated Diseases

“…Accordingly, curcumin reduces neuroinflammation in BV-2 microglial cells in an HO-1-dependent way (108). Besides, other studies demonstrated that curcumin could be useful to treat inflammatory diseases, by up-regulating HO-1 through PI3K/Akt signaling (109).…”

Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives

“…In addition, the administration of curcumin can attenuate the cytotoxicity of hemiscorpius lepturus venom, which damages the mitochondrial respiratory chain and results in ATP depletion, death signaling, and consequent cardiomyocytes apoptosis [ 157 ]. Furthermore, curcumin increases the viability of H9c2 cardiomyoblasts exposed to H 2 O 2 by upregulating the HO-1 protein, inhibiting cleaved caspase-3 protein expression, and increasing the Bcl-2/Bax ratio [ 158 ]. Additionally, curcumin prevents cardiomyocytes from high glucose-induced apoptosis via the inhibition of NADPH-mediated oxidative stress by modulating the PI3K/Akt signaling pathway [ 154 ].…”