Inhibition of long noncoding RNA BDNF-AS rescues cell death and apoptosis in hypoxia/reoxygenation damaged murine cardiomyocyte

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 (IncRNA) BDNF-AS has functional role in rescuing H/R-induced damage in cardiomyocyte in vitro. Method: 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. Conclusion: Inhibition of IncRNA BDNF-AS may be an efficient way to rescue cardiomyocyte from H/R-induced apoptosis or cell death. (c) 2017 Published by Elsevier B.V.