title: Inhibition of endoplasm reticulum stress by ghrelin protects against ischemia/reperfusion injury in rat heart.
abstract: Ghrelin is a multi-functional polypeptide with cardiovascular protective effects. We aimed to explore whether the cardioprotective effect of ghrelin is mediated by inhibiting myocardial endoplasmic reticulum stress (ERS). A Langendorff model of isolated rat heart was used with ischemia/reperfusion (I/R; 40/120 min). Cardiac function was monitored, and histomorphologic features, degree of myocardial injury, level of ERS markers, and number of apoptotic cardiomyocytes were determined. Compared with control group, the I/R group showed significantly decreased cardiac function, seriously damaged myocardial tissue, increased number of apoptotic cells, and overexpression of mRNA and protein of ERS markers. However, preadministration of ghrelin in vivo (10(-8)mol/kg, intraperitoneal injection, every 12h, twice in all) greatly ameliorated the damaged heart function, attenuated myocardial injury and apoptosis, and decreased the expression of ERS markers: it decreased the mRNA and protein levels of glucose-regulated protein78 (GRP78) and C/EBP homologous protein (CHOP), with reduced caspase-12 protein expression. Furthermore, in vitro, ghrelin directly inhibited the myocardial ERS response induced by tunicamycin or dithiothreitol in rat cardiac tissue. Ghrelin could protect the heart against I/R injury, at least in part, through inhibiting myocardial ERS.
authors.affiliation: Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Gai-Gai
authors.initials: GG
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Teng
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Ye-Bo
authors.initials: YB
authors.lastname: Zhou
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Duan
authors.forename: Jun-Qiu
authors.initials: JQ
authors.lastname: Song
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Yin
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004229:Dithiothreitol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D054439:Ghrelin / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014415:Tunicamycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D054439:Ghrelin; C000717247:HSPA5 protein, human; D014415:Tunicamycin; D004229:Dithiothreitol