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

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 2012

Fingerprint

sulfide quinone reductase
Hydrogen Sulfide
Thiosulfates
Sulfates
Brain
Thiosulfate Sulfurtransferase
Antimycin A
Animal Disease Models
Liver
Transferases
Gas Chromatography

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

Cite this

Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS. / Linden, David R; Furne, J.; Stoltz, G. J.; Abdel-Rehim, M. S.; Levitt, M. D.; Szurszewski, J. H.

In: British Journal of Pharmacology, Vol. 165, No. 7, 04.2012, p. 2178-2190.

Research output: Contribution to journalArticle

Linden, David R ; Furne, J. ; Stoltz, G. J. ; Abdel-Rehim, M. S. ; Levitt, M. D. ; Szurszewski, J. H. / Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS. In: British Journal of Pharmacology. 2012 ; Vol. 165, No. 7. pp. 2178-2190.
@article{0baaa5c166ba4508805c01c2912b5aa2,
title = "Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS",
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.",
keywords = "disulphide oxidoreductase (DiSR), enteric nervous system, gas chromatography, gasotransmitter, hydrogen sulfide (H S), protein sequestration, sulphide metabolism, sulphide oxidase, sulphide quinone reductase, thiosulphate",
author = "Linden, {David R} and J. Furne and Stoltz, {G. J.} and Abdel-Rehim, {M. S.} and Levitt, {M. D.} and Szurszewski, {J. H.}",
year = "2012",
month = "4",
doi = "10.1111/j.1476-5381.2011.01681.x",
language = "English (US)",
volume = "165",
pages = "2178--2190",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS

AU - Linden, David R

AU - Furne, J.

AU - Stoltz, G. J.

AU - Abdel-Rehim, M. S.

AU - Levitt, M. D.

AU - Szurszewski, J. H.

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - disulphide oxidoreductase (DiSR)

KW - enteric nervous system

KW - gas chromatography

KW - gasotransmitter

KW - hydrogen sulfide (H S)

KW - protein sequestration

KW - sulphide metabolism

KW - sulphide oxidase

KW - sulphide quinone reductase

KW - thiosulphate

UR - http://www.scopus.com/inward/record.url?scp=84858195283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858195283&partnerID=8YFLogxK

U2 - 10.1111/j.1476-5381.2011.01681.x

DO - 10.1111/j.1476-5381.2011.01681.x

M3 - Article

VL - 165

SP - 2178

EP - 2190

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 7

ER -