Hydrogen sulfide protects against apoptosis under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes

Nitric Oxide. 2015 Apr 30;46:204-12. doi: 10.1016/j.niox.2014.11.006. Epub 2014 Nov 25.


Oxidative stress plays a great role in the pathogenesis of heart failure (HF). Oxidative stress results in apoptosis, which can cause the damage of cardiomyocytes. Hydrogen sulfide (H2S), the third gasotransmitter, is a good reactive oxygen species (ROS) scavenger, which has protective effect against HF. Sirtuin-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that plays a critical role in promoting cell survival under oxidative stress. The purpose of this article is to investigate the interaction between H2S and SIRT1 under oxidative stress in H9c2 cardiomyocytes. Oxidative stress was induced by hydrogen peroxide (H2O2). Treatment with NaSH (25-100 µmol/L) dose-dependently increased the cell viability and improved the cell apoptosis induced by H2O2 in H9c2 cardiomyocytes. The protective effect of NaSH against the apoptosis could be attenuated by SIRT1 inhibitor Ex 527 (10 µmol/L). Treatment with NaSH (100 µmol/L) could increase the expression of SIRT1 in time dependent manner, which decreased by different concentration of H2O2. NaSH (100 µmol/L) increased the cellular ATP level and the expression of ATPase. These effects were attenuated by Ex 527 (10 µmol/L). After NaSH (100 µmol/L) treatment, the decrease in ROS production and the enhancement in SOD, GPx and GST expression were observed. Ex 527 (10 µmol/L) reversed these effects. In conclusion, for the first time, this article can identify antioxidative effects of H2S under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes.

Keywords: Hydrogen sulfide; Mitochondrial function; Oxidative stress; Sirtuin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Hydrogen Peroxide
  • Hydrogen Sulfide / pharmacology*
  • Mitochondria
  • Oxidative Stress / drug effects*
  • Rats
  • Sirtuin 1 / metabolism*


  • Hydrogen Peroxide
  • Sirt1 protein, rat
  • Sirtuin 1
  • Hydrogen Sulfide