title: 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.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Sun
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000201:enzymology*; D013440:Sulfides / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000096:biosynthesis*
chemical_list: D017382:Reactive Oxygen Species; D013440:Sulfides; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; C025451:sodium bisulfide; D006862:Hydrogen Sulfide