title: MicroRNA-214 protects against hypoxia/reoxygenation induced cell damage and myocardial ischemia/reperfusion injury via suppression of PTEN and Bim1 expression.
abstract: BACKGROUND
  Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo.
  
  
  RESULTS
  H9C2 cardiomyoblasts were transfected with lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR-control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR-control. The cells were subjected to hypoxia for 4 h followed by reoxygenation for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly increases the levels of Akt phosphorylation, markedly attenuates LDH release, and enhances the viability of the cells subjected to H/R. In vivo transfection of mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac dysfunction and reduces I/R-induced myocardial infarct size. LmiR-214 transfection significantly attenuates I/R-induced myocardial apoptosis and caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by transfection of LmiR-214 suppresses PTEN expression, increases the levels of phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in the myocardium. In addition, in vitro data shows transfection of miR-214 mimics to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to mitochondria and induces Bad phosphorylation.
  
  
  CONCLUSIONS
  Our in vitro and in vivo data suggests that miR-214 protects cells from H/R induced damage and attenuates I/R induced myocardial injury. The mechanisms involve activation of PI3K/Akt signaling by targeting PTEN expression, induction of Bad phosphorylation, and suppression of Bim1 expression, resulting in decreases in I/R-induced myocardial apoptosis.
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Race
authors.initials: R
authors.lastname: Kao
authors.affiliation: Department of Biometry and Medical Computing, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kalbfleisch
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D051025:bcl-Associated Death Protein; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D020169:Caspases; D010100:Oxygen
keywords: Bim1; PTEN; microRNA-214; myocardial apoptosis; myocardial ischemia/reperfusion injury