MicroRNA-210 alleviates oxidative stress-associated cardiomyocyte apoptosis by regulating BNIP3

Biosci Biotechnol Biochem. 2017 Sep;81(9):1712-1720. doi: 10.1080/09168451.2017.1343118. Epub 2017 Jun 29.

Abstract

Oxidative stress-induced myocardial apoptosis and necrosis are involved in ischemia/reperfusion (I/R) injury. This study was performed to investigate microRNA (miR)-210's role in oxidative stress-related myocardial damage. The expression of miR-210 was upregulated in myocardial tissues of I/R rats, while that of Bcl-2 adenovirus E1B 19kDa-interacting protein 3 (BNIP3) was downregulated. To simulate in vivo oxidative stress, H9c2 cells were treated with H2O2 for 48 h. MiR-210 level was increased upon H2O2 stimulation, peaked at 8 h, and then decreased. An opposite expression pattern of BNIP3 was observed. BNIP3 was demonstrated as a direct target of miR-210 via luciferase reporter assay. H2O2-induced cell apoptosis was attenuated by miR-210 mimics, whereas aggravated by miR-210 inhibitor. MiR-210 knockdown-induced cell apoptosis in presence of H2O2 was attenuated by BNIP3 siRNA. Our work demonstrates that miR-210 plays a protective role in H2O2-induced cardiomyocyte apoptosis at least by regulating the pro-apoptotic BNIP3.

Keywords: Bcl-2 adenovirus E1B 19kDa-interacting protein 3; ischemia/reperfusion; miR-210; myocardial apoptosis; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Line
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Knockdown Techniques
  • Hydrogen Peroxide / pharmacology
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • MicroRNAs / genetics*
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • Rats
  • Rats, Wistar

Substances

  • BNIP3 protein, rat
  • MIRN210 microRNA, rat
  • Membrane Proteins
  • MicroRNAs
  • Mitochondrial Proteins
  • Hydrogen Peroxide