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

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.