title: Heme oxygenase 1 induction protects myocardiac cells against hypoxia/reoxygenation-induced apoptosis : The role of JNK/c-Jun/Caspase-3 inhibition and Akt signaling enhancement.
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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China. biolichengqiu@126.com.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Xuan
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China.
authors.forename: C
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, 59 Qianquan Road, 273500, Jining, Shandong, P.R. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
chemical_list: D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: Akt signaling pathway; Apoptosis; Cardiac myocytes; Heme oxygenase-1; Zinc protoporphyrin