title: MicroRNA-133b-5p Is Involved in Cardioprotection of Morphine Preconditioning in Rat Cardiomyocytes by Targeting Fas.
abstract: MicroRNAs (miRNAs) have been implicated in ischemia-reperfusion injury and ischemic preconditioning. Opioid pre- and postconditioning have powerful protective effects on the heart, but it is still not known whether miRNAs are involved in opioid-induced cardioprotection. The present study was designed to investigate the role of miRNAs in morphine preconditioning (MPC)-induced cardioprotection.
  
  
  
  MiRNA microarray analysis was performed to examine the differentially expressed miRNAs caused by MPC in adult rat cardiomyocytes. A dual-luciferase reporter assay was performed to confirm the direct regulation of miR-133b-5p on the target gene Fas. MiR-133b-5p mimic or inhibitor was separately transfected into myocardial H9c2 cells to examine the role of miR-133b-5p in morphine-induced cardioprotection.
  
  
  
  MPC protected adult rat cardiomyocytes against hypoxia/reoxygenation (H/R) injury by reducing cell injury and death. MiRNA microarray data showed that a total of 39 miRNAs were differentially expressed after MPC treatment. A Dual-luciferase reporter assay confirmed that miR-133b-5p directly targets the Fas gene. After H/R injury, the decrease in miR-133b-5p and a contemporaneous rise in Fas mRNA and protein levels in adult rat cardiomyocytes were prevented by MPC treatment. In H9c2 cardiomyocytes, overexpression of miR-133b-5p reduced H/R-induced cell injury and apoptosis by inhibiting Fas expression. Knockdown of miR-133b-5p blocked morphine-mediated cardioprotection by reducing miR-133b-5p levels while enhancing the expression of Fas mRNA and protein.
  
  
  
  MPC causes a change in miRNA expression in rat cardiomyocytes. Morphine may protect cardiomyocytes against H/R injury through upregulation of miR-133b-5p by targeting Fas.
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: He
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China; Department of Anaesthesiology, Anhui Women and Child Health Care Hospital, Hefei, China.
authors.forename: Hai-Juan
authors.initials: HJ
authors.lastname: Zhu
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Han
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Shi-Yun
authors.initials: SY
authors.lastname: Jin
authors.affiliation: Department of Anaesthesiology, University of Hong Kong, Hong Kong, China.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.affiliation: Department of Anaesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: zhangye_hassan@aliyun.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D023421:Models, Animal; D009020:Morphine / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; C491898:Fas protein, rat; C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D019014:fas Receptor; D009020:Morphine