title: Salusins protect myocardium against ischemic injury by alleviating endoplasmic reticulum stress.
abstract: Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-α and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery (LAD), salusin-α or -β was intravenously injected at 5 or 15 nmol kg(-1) 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD occlusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg(-1) salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the activation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP (C/EBP homologous protein), and attenuated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myocardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis.
authors.affiliation: Department of Physiology and Neurobiology, Basic Medical College, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shifu
authors.initials: S
authors.lastname: Shan
authors.forename: Tiantian
authors.initials: T
authors.lastname: Hu
authors.forename: Huyan
authors.initials: H
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Anjing
authors.initials: A
authors.lastname: Ren
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D006360:Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051742:Transcription Factor CHOP; D014415:Tunicamycin; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C528274:salusin-beta, rat