BACKGROUND AND PURPOSEHydrogen sulphide (H2S) is gaining acceptance as a gaseous signal molecule. However, mechanisms regarding signal termination are not understood. We used stigmatellin and antimycin A, inhibitors of sulphide quinone reductase (SQR), to test the hypothesis that the catabolism of H2S involves SQR.
EXPERIMENTAL APPROACHH2S production and consumption were determined in living and intact mouse brain, liver and colonic muscularis externa using gas chromatography and HPLC. Expressions of SQR, ethylmalonic encephalopathy 1 (Ethe1) and thiosulphate transferase (TST; rhodanese) were determined by RT-PCR and immunohistochemistry.
KEY RESULTSIn the colonic muscularis externa, H2 S that was probably bound to proteins. Levels of mRNA encoding SQR were higher in the colonic muscularis externa and the liver than in the brain.
CONCLUSIONS AND IMPLICATIONSThese data support the concept that termination of endogenous H2S signalling in the colonic muscularis externa occurs via catabolism to thiosulphate and sulphate partially via a mechanism involving SQR. In the brain, it appears that H2S signal termination occurs partially through protein sequestration and partially through catabolism not involving SQR. As H2S has beneficial effects in animal models of human disease, we suggest that selective inhibition of SQR is an attractive target for pharmaceutical development.
AbbreviationsDiSR, disulphide oxidoreductase flavoprotein; DTT, dithiothreitol; Ethe1, ethylmalonic encephalopathy 1; FCCP, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; GOI, gene of interest; HKG, housekeeping genes; SQR, sulphide quinone reductase; Sqrdl, sulphide quinone reductase domain-like; TRP, transient receptor potential; TST, thiosulphate sulphur transferase BJP British Journal of Pharmacology
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.