title: Globular adiponectin attenuates myocardial ischemia/reperfusion injury by upregulating endoplasmic reticulum Ca²⁺-ATPase activity and inhibiting endoplasmic reticulum stress.
abstract: OBJECTIVE
  The aim of this study was to explore the mechanisms underlying the effects of globular adiponectin (gAd) on myocardial ischemia/reperfusion (I/R) injury.
  
  
  METHODS
  An in vivo myocardial I/R model and an in vitro neonatal rat cardiomyocyte hypoxia/reoxygenation (H/R) model simulating I/R injury in vivo were adopted to investigate whether and how the cardioprotective effects of gAd are mediated by the inhibition of endoplasmic reticulum (ER) stress.
  
  
  RESULTS
  gAd (1 μg/g, intravenously) attenuated the myocardial infarct size, myocardial enzyme activity, and apoptosis in rats with I/R, and similar protection was observed in primary cultures of neonatal rat cardiomyocytes. The protective effects of gAd were associated with the suppression of ER stress, as evidenced by reversing the upregulation of 78-kDa glucose-regulated protein, C/EBP homologous protein, and caspase-12 that were induced by H/R and thapsigargin. In addition, gAd conferred resistance to ER stress and cardiomyocyte injury by modulating ER Ca²⁺-ATPase (SERCA) activity. Moreover, gAd further increased H/R-enhanced Akt phosphorylation. The protective effects of gAd on ER stress and SERCA activity were abolished by preincubation of rat neonatal cardiomyocytes with the PI3K inhibitor LY294002. Consistent with this finding, I/R-induced ER stress and SERCA dysfunction were also significantly ameliorated by gAd. These effects involved PI3K/Akt signaling pathway.
  
  
  CONCLUSIONS
  The protective effects of gAd during I/R are mediated, at least in part, by modulating SERCA activity and consequently suppressing ER stress via the activation of PI3K/Akt signaling.
authors.affiliation: Simulation Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Bian
authors.forename: Rui
authors.initials: R
authors.lastname: Bai
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Minghuan
authors.initials: M
authors.lastname: Fu
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D002316:Cardiotonic Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; C544418:adiponectin (110-244), human; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases