title: Inhibition of long noncoding RNA BDNF-AS rescues cell death and apoptosis in hypoxia/reoxygenation damaged murine cardiomyocyte.
abstract: BACKGROUND
  Hypoxia/reoxygenation (H/R)-induced cardiomyocyte damage in vitro bears many similarities to myocardial infraction in vivo. In this study, we investigated whether long noncoding RNA (lncRNA) BDNF-AS has functional role in rescuing H/R-induced damage in cardiomyocyte in vitro.
  
  
  METHODS
  Murine neonatal cardiomyocytes were cultured in vitro, and treated with either long (Hypoxia (L)) or short (Hypoxia (S)) H/R conditions. Viability and TUNEL assays were conducted to assess cardiomyocyte death or apoptosis. QRT-PCR was used to examine BDNF-AS mRNA expression. Endogenous BDNF-AS was downregulated by siRNA in cardiomyocyte. Its effect on H/R-induced cardiomyocyte damage was then examined. In addition, survival-associated proteins, including BDNF, VEGF and Akt were examined by western blot in siRNA-transfected cardiomyocytes.
  
  
  RESULTS
  Hypoxia (S) induced apoptosis whereas Hypoxia (L) induced cell death in murine neonatal cardiomyocyte in vitro. Under both conditions, endogenous cardiomyocyte BDNF-AS was significantly upregulated. SiRNA-mediated BDNF-AS downregulation rescued cardiomyocyte death under Hypoxia (L) condition, and reduced cardiomyocyte apoptosis under Hypoxia (L) condition. Moreover, BDNF-AS downregulation activated BDNF and VEGF through upregulation, and activated Akt through phosphorylation in H/R-damaged cardiomyocyte.
  
  
  CONCLUSIONS
  Inhibition of lncRNA BDNF-AS may be an efficient way to rescue cardiomyocyte from H/R-induced apoptosis or cell death.
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Soochow University, 213000, Changzhou, China. Electronic address: ellazhao8@aol.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Vascular Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Soochow University, 213000, Changzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Soochow University, 213000, Changzhou, China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Soochow University, 213000, Changzhou, China.
authors.forename: Qunli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Soochow University, 213000, Changzhou, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Soochow University, 213000, Changzhou, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D000860:Hypoxia; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016372:RNA, Antisense / Q000037:antagonists & inhibitors / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
keywords: Apoptosis; BDNF-AS; Cardiomyocyte; Cell death; Hypoxia; Reoxygenation