title: RISK pathway is involved in oxytocin postconditioning in isolated rat heart.
abstract: The reperfusion injury salvage kinase (RISK) pathway is a fundamental signal transduction cascade in the cardioprotective mechanism of ischemic postconditioning. In the present study, we examined the cardioprotective role of oxytocin as a postconditioning agent via activation of the RISK pathway (PI3K/Akt and ERK1/2). Animals were randomly divided into 6 groups. The hearts were subjected under 30minutes (min) ischemia and 100min reperfusion. OT was perfused 15min at the early phase of reperfusion. RISK pathway inhibitors (Wortmannin; an Akt inhibitor, PD98059; an ERK1/2 inhibitor) and Atosiban (an OT receptor antagonist) were applied either alone 10min before the onset of the ischemia or in the combination with OT during early reperfusion phase. Myocardial infarct size, hemodynamic factors, ventricular arrhythmia, coronary flow and cardiac biochemical marker were measured at the end of reperfusion. OT postconditioning (OTpost), significantly decreased the infarct size, arrhythmia score, incidence of ventricular fibrillation, Lactate dehydrogenase and it increased coronary flow. The cardioprotective effect of OTpos was abrogated by PI3K/Akt, ERK1/2 inhibitors and Atosiban. Our data have shown that OTpost can activate RISK pathway mostly via the PI3K/Akt and ERK1/2 signaling cascades during the early phase of reperfusion.
authors.affiliation: Student Research Committee, Department of Modern Science and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mirali
authors.initials: M
authors.lastname: Polshekan
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Kadijeh
authors.initials: K
authors.lastname: Jamialahmadi
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: vaph99@yahoo.com.
authors.forename: Vahid
authors.initials: V
authors.lastname: Khori
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.affiliation: Stem cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Saeidi
authors.affiliation: Biochemistry of Nutrition Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.affiliation: Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Jand
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Yazdani
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D057775:Ischemic Postconditioning; D020935:MAP Kinase Signaling System; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D065840:Protective Factors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D010121:Oxytocin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Isolated heart preparation; Myocardial ischemia; Myocardial reperfusion injury; Oxytocin