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

D. R. Linden, J. Furne, G. J. Stoltz, M. S. Abdel-Rehim, M. D. Levitt, J. H. Szurszewski

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

BACKGROUND AND PURPOSE Hydrogen sulphide (H 2S) 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 H 2S involves SQR. EXPERIMENTAL APPROACH H 2S 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 RESULTS In the colonic muscularis externa, H 2 35S was catabolized to [ 35S]-thiosulphate and [ 35S]-sulphate, and stigmatellin reduced both the consumption of H 2 35S and formation of [ 35S]-thiosulphate. Stigmatellin also enhanced H 2S release by the colonic muscularis externa. In the brain, catabolism of H 2 35S to [ 35S]-thiosulphate and [ 35S]-sulphate, which was stigmatellin-insensitive, partially accounted for H 2 35S 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 IMPLICATIONS These data support the concept that termination of endogenous H 2S 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 H 2S signal termination occurs partially through protein sequestration and partially through catabolism not involving SQR. As H 2S has beneficial effects in animal models of human disease, we suggest that selective inhibition of SQR is an attractive target for pharmaceutical development.

Original languageEnglish (US)
Pages (from-to)2178-2190
Number of pages13
JournalBritish Journal of Pharmacology
Volume165
Issue number7
DOIs
StatePublished - Apr 1 2012

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Keywords

  • disulphide oxidoreductase (DiSR)
  • enteric nervous system
  • gas chromatography
  • gasotransmitter
  • hydrogen sulfide (H S)
  • protein sequestration
  • sulphide metabolism
  • sulphide oxidase
  • sulphide quinone reductase
  • thiosulphate

ASJC Scopus subject areas

  • Pharmacology

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