Heme oxygenase 1 induction protects myocardiac cells against hypoxia/reoxygenation-induced apoptosis

Background Although recent studies have found that heme oxygenase (HO)-1 plays an important role in myocardiac cell survival, the precise mechanisms occurring during hypoxia/reoxygenation (H/R) injury remain unclear. Therefore, the aim of this study was to investigate the cytoprotective mechanisms of HO-1 against H/R-induced myocardiac cell apoptosis and to explore whether the Akt signaling pathway contributed to the protection provided by HO-1. Methods Cobalt protoporphyrin (CoPP, a pharmacologic inducer of HO-1) was employed to induce the over-expression of HO-1 before H/R in H9c2 cells. Hoechst staining and flow cytometry were used to examine the extent of apoptosis. Furthermore, the effect of HO-1 on Akt, JNK, and the expression of apoptosis-related proteins (c-JUN and Caspase-3) was determined by Western blotting. Results The results showed that over-expressed HO-1 could significantly protect myocardiac cells against H/R-induced apoptosis in H9c2 cells. Furthermore, the protein expression of p‑Akt increased and of p‑JNK decreased in the H/R injury H9c2 cells when treated with CoPP. The apoptosis-related proteins c‑Jun and caspase-3 were both inhibited by over-expression of HO-1. At the same time, retreatment with zinc protoporphyrin (ZnPP, a specific inhibitor of HO-1 enzymatic activity) or LY294002 (an inhibitor of Akt1) reversed the HO-1-induced changes. Conclusion In summary, our results suggest that HO-1 can decrease H/R-induced myocardiac cell apoptosis; the mechanism may be related to the activation of the Akt signaling pathway and, furthermore, to the inhibition of the JNK/c-Jun/caspase-3 signaling pathway.