title: Spermine inhibits Endoplasmic Reticulum Stress-induced Apoptosis: a New Strategy to Prevent Cardiomyocyte Apoptosis.
abstract: OBJECTIVE
  Endoplasmic reticulum stress (ERS) plays an important role in the progression of acute myocardial infarction (AMI), in part by mediating apoptosis. Polyamines, including putrescine, spermidine, and spermine, are polycations with anti-oxidative, anti-aging, and cell growth-promoting activities. This study aimed to determine the mechanisms by which spermine protects against ERS-induced apoptosis in rats following AMI.
  
  
  RESULTS
  AMI was established by ligation of the left anterior descending coronary artery (LAD) in rats, and exogenous spermine was administered by intraperitoneal injection (2.5 mg/ml daily for 7 days pre-AMI). Spermine treatment limited infarct size, attenuated cardiac troponin I and creatinine kinase-MB release, improved cardiac function, and decreased ERS and apoptosis related protein expression. Isolated cardiomyocytes subjected to hypoxia showed significant increase in reactive oxygen species (ROS) and the expression of apoptosis and ERS related proteins; these effects occurred through PERK and eIF2α phosphorylation. The addition of spermine attenuated cardiomyocyte apoptosis, suppressed the production of ROS, and inhibited ERS related pathways.
  
  
  CONCLUSIONS
  Spermine was an effective pre-treatment strategy to attenuate cardiac ERS injury in rats, and the cardioprotective mechanism occurring through inhibition of ROS production and down regulation of the PERK-eIF2α pathway. These findings provide a novel target for the prevention of apoptosis in the setting of AMI.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wei
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.forename: Meixiu
authors.initials: M
authors.lastname: Li
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Li
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Lu
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Shao
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013096:Spermine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019210:Troponin I / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019210:Troponin I; D013096:Spermine