title: Ghrelin protected neonatal rat cardiomyocyte against hypoxia/reoxygenation injury by inhibiting apoptosis through Akt-mTOR signal.
abstract: Reducing reperfusion period myocardial cell damage is efficient to reduce myocardial ischemia-reperfusion injury. Ghrelin can increase myocardial contractility, improve heart failure caused by myocardial infarction. This study aimed to investigate the protective effect of Ghrelin on myocardial hypoxia/reoxygenation (H/R) injury of neonatal rat cardiomyocytes (NRCMs) and to explore the mechanisms. We isolated the NRCMs, established myocardial H/R model, blocked growth hormone secretagogue receptor (GHSR) by siRNA technique, examined cell activity by MTT and LDH assay, detected apoptosis by Hoechst 33258 staining and flow cytometry and determined the expression levels of apoptosis related proteins and signaling pathway proteins by western blot. We found that Ghrelin can significantly improve cell activity and decrease apoptosis after H/R, however this effect was abolished by GHSR-siRNA. In addition, we found that Ghrelin can significantly increase the expression of Bcl-2 but inhibit the level of Bax and caspase-3. Further mechanism study found that the phosphorylation level of signaling pathway protein Akt and mTOR in Ghrelin treated group were significantly higher than that in other groups. In conclusion, Ghrelin can reduce the H/R damage on NRCMs and inhibit the apoptosis by activating Akt-mTOR signaling pathway.
authors.affiliation: Department of Cardiology, The Fourth Clinical Hospital of Harbin Medical University, No. 37 Yiyuan Road, Nangang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Fourth Clinical Hospital of Harbin Medical University, No. 37 Yiyuan Road, Nangang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Cardiology, The Fourth Clinical Hospital of Harbin Medical University, No. 37 Yiyuan Road, Nangang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Fourth Clinical Hospital of Harbin Medical University, No. 37 Yiyuan Road, Nangang District, Harbin, 150001, Heilongjiang, China. liulx0330@163.com.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D000860:Hypoxia / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D054439:Ghrelin; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546845:mTOR protein, rat
keywords: Apoptosis; Ghrelin; Hypoxia/reoxygenation injury; Neonatal rat cardiomyocytes