title: Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS.
abstract: OBJECTIVE
  Hydrogen sulphide (H(2) S) 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(2) S involves SQR.
  
  
  METHODS
  H(2) S 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.
  
  
  RESULTS
  In the colonic muscularis externa, H(2) (35) S was catabolized to [(35) S]-thiosulphate and [(35) S]-sulphate, and stigmatellin reduced both the consumption of H(2) (35) S and formation of [(35) S]-thiosulphate. Stigmatellin also enhanced H(2) S release by the colonic muscularis externa. In the brain, catabolism of H(2) (35) S to [(35) S]-thiosulphate and [(35) S]-sulphate, which was stigmatellin-insensitive, partially accounted for H(2) (35) S consumption, while the remainder was captured as unidentified (35) 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
  These data support the concept that termination of endogenous H(2) S 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(2) S signal termination occurs partially through protein sequestration and partially through catabolism not involving SQR. As H(2) S has beneficial effects in animal models of human disease, we suggest that selective inhibition of SQR is an attractive target for pharmaceutical development.
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA. Linden.David@mayo.edu
authors.forename: D R
authors.initials: DR
authors.lastname: Linden
authors.forename: J
authors.initials: J
authors.lastname: Furne
authors.forename: G J
authors.initials: GJ
authors.lastname: Stoltz
authors.forename: M S
authors.initials: MS
authors.lastname: Abdel-Rehim
authors.forename: M D
authors.initials: MD
authors.lastname: Levitt
authors.forename: J H
authors.initials: JH
authors.lastname: Szurszewski
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology; D011808:Quinone Reductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013431:Sulfates / Q000378:metabolism; D013884:Thiosulfate Sulfurtransferase / Q000235:genetics / Q000378:metabolism; D013885:Thiosulfates / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004791:Enzyme Inhibitors; D024101:Mitochondrial Proteins; D011090:Polyenes; D012333:RNA, Messenger; D013431:Sulfates; D013885:Thiosulfates; D000968:Antimycin A; C041573:stigmatellin; D049308:Dioxygenases; C538757:ETHE1 protein, mouse; D011808:Quinone Reductases; C073412:sulfide quinone reductase; D013884:Thiosulfate Sulfurtransferase; D006862:Hydrogen Sulfide