title: Ghrelin protects H9c2 cardiomyocytes from angiotensin II-induced apoptosis through the endoplasmic reticulum stress pathway.
abstract: Ghrelin, a gastric hormone, exerts cardioprotective function by increasing myocardial contractility and vasodilation. Previous studies have reported that angiotensin II (Ang II) production increased in heart failure, which can induce cardiomyocyte apoptosis. In this study, we investigated the effect of ghrelin on Ang II-induced H9c2 cardiomyocyte apoptosis. The results showed that Ang II inhibited H9c2 cell viability, which was blocked by ghrelin. By annexin V-propidium iodide dual staining and 2'-deoxyuridine 5'-triphosphate nick end-labeling analysis, we found that Ang II induced H9c2 cell apoptosis, whereas coincubation of ghrelin with Ang II significantly reduced H9c2 cell apoptosis induced by Ang II. Simultaneously, the results revealed that ghrelin regulated the Ang II-induced imbalance of Bax and Bcl-2 expression and reduced Ang II-induced caspase-3 expression. Moreover, mRNA expressions of endoplasmic reticulum stress-related molecules GRP78, caspase-12, and C/EBP homologous protein were significantly upregulated by Ang II. However, their expressions were significantly inhibited by ghrelin. In addition, we found that ghrelin markedly inhibited Ang II-induced Ang II type 1 receptor expression. These data suggest that ghrelin may play an antagonistic role in Ang II-induced cardiomyocyte apoptosis via decreasing Ang II type 1 receptor expression and inhibiting the activation of endoplasmic reticulum stress pathway.
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D054439:Ghrelin; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D051028:bcl-2-Associated X Protein; D000804:Angiotensin II; D053148:Caspase 3