Hydrogen Sulfide and Cell Signaling

Abstract

Hydrogen sulfide (H2S) is a gaseous mediator synthesized from cysteine by cystathionine γ lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H2S donors and genetic experiments using CSE knockout mice suggest important roles for this vasodilator gas in the regulation of blood vessel caliber, cardiac response to ischemia/reperfusion injury, and inflammation. That H2S inhibits cytochrome c oxidase and reduces cell energy production has been known for many decades, but more recently, a number of additional pharmacological targets for this gas have been identified. H2S activates KATP and transient receptor potential (TRP) channels but usually inhibits big conductance Ca2+-sensitive K+ (BKCa) channels, T-type calcium channels, and M-type calcium channels. H2S may inhibit or activate NF-κB nuclear translocation while affecting the activity of numerous kinases including p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and Akt. These disparate effects may be secondary to the well-known reducing activity of H2S and/or its ability to promote sulfhydration of protein cysteine moieties within the cell.