Hydrogen sulfide decreases the levels of ROS by inhibiting mitochondrial complex IV and increasing SOD activities in cardiomyocytes under ischemia/reperfusion

Biochem Biophys Res Commun. 2012 May 4;421(2):164-9. doi: 10.1016/j.bbrc.2012.03.121. Epub 2012 Apr 7.

Abstract

Inhibition of oxidative stress has been reported to be involved in the cardioprotective effects of hydrogen sulfide (H(2)S) during ischemia/reperfusion (I/R). However, the mechanism whereby H(2)S regulates the level of cardiac reactive oxygen species (ROS) during I/R remains unclear. Therefore, we investigated the effects of H(2)S on pathways that generate and scavenge ROS. Our results show that pretreating rat neonatal cardiomyocytes with NaHS, a H(2)S donor, reduced the levels of ROS during the hypoxia/reoxygenation (H/R) condition. We found that H(2)S inhibited mitochondrial complex IV activity and increased the activities of superoxide dismutases (SODs), including Mn-SOD and CuZn-SOD. Further studies indicated that H(2)S up-regulated the expression of Mn-SOD but not CuZn-SOD. Using a cell-free system, we showed that H(2)S activates CuZn-SOD. An isothermal titration calorimetry (ITC) analysis indicated that H(2)S directly interacts with CuZn-SOD. Taken together, H(2)S inhibits mitochondrial complex IV and activates SOD to decrease the levels of ROS in cardiomyocytes during I/R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytoprotection*
  • Electron Transport Complex IV / antagonists & inhibitors*
  • Hydrogen Sulfide / metabolism*
  • Mitochondria / enzymology*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reperfusion Injury / enzymology*
  • Sulfides / pharmacology
  • Superoxide Dismutase / biosynthesis*

Substances

  • Reactive Oxygen Species
  • Sulfides
  • Superoxide Dismutase
  • Electron Transport Complex IV
  • sodium bisulfide
  • Hydrogen Sulfide