Rhodanese, but not cystathionine-gamma-lyase, is associated with dextran sulfate sodium-evoked colitis in mice: a sign of impaired colonic sulfide detoxification?

Abstract

Clinical studies suggest that colonic luminal hydrogen sulfide (H(2)S), produced by sulfate-reducing bacteria or through other pathways, might be involved in the pathogenesis of inflammatory bowel disease (IBD). Nonetheless, this hypothesis has been poorly investigated by basic studies using laboratory animals. We thus focused on two enzymes, cystathionine-gamma-lyase (CSE) that generates H(2)S from l-cysteine, and rhodanese that directly or indirectly detoxifies H(2)S, particularly in relation to the colitis induced by dextran sulfate sodium (DSS) in mice. CSE was a major H(2)S-forming enzyme in colonic and renal homogenates from mice and rats, and the rhodanese activity was also detectable in both tissues. Colitis-related symptoms including decreased body weight gain, diarrhea, hematochezia and shortening of colon length were observed in the mice drinking DSS. Those symptoms were not or only slightly attenuated by repeated administration of a CSE inhibitor. CSE activity and protein levels in the colonic tissue did not notably change in the mice with colitis. In contrast, the activity and protein/mRNA levels of rhodanese in the colon, but not kidney, significantly decreased nearly in parallel with the development of colitis, followed by elevation of rhodanese activity in red blood cells (RBCs). These data show that rhodanese, but not CSE, is associated with DSS-induced colitis in mice, leading to a hypothesis that impaired detoxification of H(2)S due to down-regulation or suppression of colonic rhodanese is involved in IBD. The delayed enhancement of rhodanese activity in RBCs, a possible compensative event, might be available as a disease marker for IBD.

• Authors: Eiichi Taniguchi, Maho Matsunami, Takeshi Kimura, Daiki Yonezawa, Tsuyoshi Ishiki, Fumiko Sekiguchi, Hiroyuki Nishikawa, Yuma Maeda, Hiroyasu Ishikura, Atsufumi Kawabata
• Journal: Toxicology (Toxicology) Vol. 264 Issue 1-2 Pg. 96-103 (Oct 01 2009) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 19647029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Elsevier Ireland Ltd.

Chemical References

• Sulfides
• RNA
• Dextran Sulfate
• Thiosulfate Sulfurtransferase
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Anemia (blood)
• Animals
• Blotting, Western
• Colitis (chemically induced, enzymology, pathology)
• Colon (metabolism, pathology)
• Cystathionine gamma-Lyase (blood, metabolism)
• Dextran Sulfate (toxicity)
• Erythrocytes (drug effects, enzymology)
• Hydrogen Sulfide (metabolism)
• Inactivation, Metabolic
• Male
• Mice
• RNA (biosynthesis, genetics)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Sulfides (metabolism, toxicity)
• Thiosulfate Sulfurtransferase (blood, metabolism)
• Weight Gain (drug effects)