title: Morphine Postconditioning Protects Against Reperfusion Injury: the Role of Protein Kinase C-Epsilon, Extracellular Signal-Regulated Kinase 1/2 and Mitochondrial Permeability Transition Pores.
abstract: OBJECTIVE
  The purpose of this study was to investigate the implications of protein kinase C-epsilon (PKCε), Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and mitochondrial permeability transition pore (mPTP) in myocardial protection induced by morphine postconditioning (MpostC).
  
  
  METHODS
  The isolated rat hearts were randomly assigned into one of eight groups. Hearts in time control (TC) group were constantly perfused for 105min. Hearts in ischemia-reperfusion (I/R) group were subjected to 45 min of ischemia followed by 1 h of reperfusion. MpostC was induced by 10 min of morphine administration at the onset of reperfusion. εV1-2 (an inhibitor of PKCε) and PD (an inhibitor of ERK1/2) was administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. I/R injury was assessed by functional parameters, creatine kinase-MB (CK-MB) release and infarct size (IS/AAR). Additional hearts were excised at 20 min following reperfusion to detect the membrane-specific translocation of PKCε, ERK1/2 phosphorylation, mitochondrial permeability transition (MPT) and cytochrome C (Cyt-c) release.
  
  
  RESULTS
  MpostC markedly reduced infarct size (IS/AAR), CK-MB release, and improved cardiac function recovery. However, these protective effects were partly abolished in the presence of εV1-2 or PD. Compared to TC group, the membrane translocation of PKCε, ERK1/2 phosphorylation, mPTP opening, and Cyt-c release were significantly increased in I/R hearts. MpostC further increased the membrane translocation of PKCε and ERK1/2 phosphorylation, and significantly inhibited mPTP opening and Cyt-c release. However, those protective effects induced by MpostC were abolished by εV1-2 or PD, which, used alone, showed no influence on reperfusion injury.
  
  
  CONCLUSIONS
  These findings suggest that MpostC protects isolated rat hearts against ischemia-reperfusion injury via activating PKCε-ERK1/2 pathway and inhibiting mPTP opening.
authors: Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors: Zuolei
authors: Z
authors: Chen
authors: Donat R
authors: DR
authors: Spahn
authors: Xuewei
authors: X
authors: Zhang
authors: Yingzhi
authors: Y
authors: Liu
authors: Haichen
authors: H
authors: Chu
authors: Zhongkai
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005786:Gene Expression Regulation; D057775:Ischemic Postconditioning / Q000379:methods; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010446:Peptide Fragments; C448318:epsilonV1-2 peptide; D009020:Morphine; D045304:Cytochromes c; D051744:Protein Kinase C-epsilon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D052279:Creatine Kinase, MB Form