Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS

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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, H235S was catabolized to [35S]-thiosulphate and [35S]-sulphate, and stigmatellin reduced both the consumption of H235S and formation of [35S]-thiosulphate. Stigmatellin also enhanced H2S release by the colonic muscularis externa. In the brain, catabolism of H235S to [35S]-thiosulphate and [35S]-sulphate, which was stigmatellin-insensitive, partially accounted for H235S consumption, while the remainder was captured as unidentified 35S 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.

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