NOX2 Antisense Attenuates Hypoxia-Induced Oxidative Stress and Apoptosis in Cardiomyocyte

Int J Med Sci. 2016 Jul 27;13(8):646-52. doi: 10.7150/ijms.15177. eCollection 2016.

Abstract

Heart ischemia is a hypoxia related disease. NOX2 and HIF-1α proteins were increased in cardiomyocytes after acute myocardial infarction. However, the relationship of the hypoxia-induced HIF-1α. NOX2-derived oxidative stress and apoptosis in cardiomyocyte remains unclear. In the current study, we use NOX2 antisense strategy to investigate the role of NOX2 in hypoxia-induced oxidative stress and apoptosis in rat cardiomyocytes. Here, we show that transduction of ADV-NOX2-AS induces potent silencing of NOX2 in cardiomyocytes, and resulting in attenuation of hypoxia-induced oxidative stress and apoptosis. This study indicates the potential of antisense-based therapies and validates NOX2 as a potent therapeutic candidate for heart ischemia.

Keywords: Heart infarction; Heart ischemia; NOX2; Oxidative stress; and apoptosis.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Hypoxia / genetics
  • Disease Models, Animal
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics*
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy
  • Myocardial Reperfusion Injury / genetics*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / therapy
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • NADPH Oxidase 2
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / genetics*
  • Oligonucleotides, Antisense / isolation & purification*
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / therapeutic use
  • Oxidative Stress / genetics
  • Rats

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Glycoproteins
  • Oligonucleotides, Antisense
  • Cybb protein, rat
  • NADPH Oxidase 2
  • NADPH Oxidases