Hydrogen sulfide mediates athero-protection against oxidative stress via S-sulfhydration

S-sulfhydration is a signalling pathway of hydrogen sulfide (H(2)S), which is suggested as an anti-atherogenic molecule that may protect against atherosclerosis. The identification of S-sulfhydrated proteins by proteomic approach could be a major step towards understanding the mechanisms of H(2)S in response to atherosclerosis. The present study studied targeted S-sulfhydrated proteins using the modified biotin switch method followed by matrix-assisted laser desorption/ionisation time of flight tandem mass spectrometry identification. The results showed that H(2)S can protect against atherosclerosis by reducing body weight gain and alleviating aortic plaque formation. In addition, H(2)S treatment can increase aortic protein S-sulfhydration. Seventy targeted S-sulfhydrated aortic proteins were identified, mainly involved in metabolism, stimulus response and biological regulation, as determined by gene ontology database analysis. H(2)S also induced S-sulfhydration of glutathione peroxidase 1 and further reduced lipid peroxidation and increased antioxidant defence in the aorta by prompting glutathione synthesis. Our data suggest that H(2)S is a cardiovascular-protective molecule that S-sulfhydrates a subset of proteins that are mainly responsible for lipid metabolism and exerts its cytoprotective effects to clear free radicals and inhibit oxidative stress through cysteine S-sulfhydration.