C Li1, C Zhang2, T Wang2, J Xuan2, C Su2, Y Wang2. 1. Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China. biolichengqiu@126.com. 2. Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China.
Abstract
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.
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.
Authors: Päivi Lakkisto; Juha-Matti Siren; Ville Kytö; Hanna Forsten; Mika Laine; Kari Pulkki; Ilkka Tikkanen Journal: Exp Biol Med (Maywood) Date: 2011-11-15
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