Hydrogen Sulfide and Cell Signaling

Abstract

Hydrogen sulfide (H 2 S) is a gaseous mediator synthesized from cysteine by cystathionine γ lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H 2 S 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 H 2 S 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. H 2 S activates K ATP and transient receptor potential (TRP) channels but usually inhibits big conductance Ca 2+ -sensitive K + (BK Ca ) channels, T-type calcium channels, and M-type calcium channels. H 2 S 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 H 2 S and/or its ability to promote sulfhydration of protein cysteine moieties within the cell.