Inhibition of endoplasm reticulum stress by ghrelin protects against ischemia/reperfusion injury in rat heart.
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.
Zhang
Gai-Gai
GG
Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Teng
Xu
X
Liu
Yue
Y
Cai
Yan
Y
Zhou
Ye-Bo
YB
Duan
Xiao-Hui
XH
Song
Jun-Qiu
JQ
Shi
Yi
Y
Tang
Chao-Shu
CS
Yin
Xin-Hua
XH
Qi
Yong-Fen
YF
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
D000091342:Endoplasmic Reticulum Chaperone BiP; D054439:Ghrelin; C000717247:HSPA5 protein, human; D014415:Tunicamycin; D004229:Dithiothreitol