Mucosal protection against sulphide: importance of the enzyme rhodanese

Picton, Rhian

doi:10.1136/gut.50.2.201

Cited by 103 publications

(75 citation statements)

References 19 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31). Sodium sulfide had a %C1/2 value of 368.6 Amol/L, indicating that Na 2 S is a moderate cytotoxic agent when compared with a previously published cytotoxicity library (31,32 (37) or constant cell removal may be the strategy that the intestinal epithelium follows to maintain its integrity. It is also noticeable that the %C1/2 value is much higher than the 50 Amol/L previously reported to inhibit mitachondrial oxidative phosphorylation (38).…”

Section: Resultsmentioning

confidence: 84%

Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Attene‐Ramos¹,

Wagner

Plewa

et al. 2006

Molecular Cancer Research

301

204

View full text Add to dashboard Cite

Hydrogen sulfide (H 2 S) produced by commensal sulfate-reducing bacteria, which are often members of normal colonic microbiota, represents an environmental insult to the intestinal epithelium potentially contributing to chronic intestinal disorders that are dependent on gene-environment interactions. For example, epidemiologic studies reveal either persistent sulfate-reducing bacteria colonization or H 2 S in the gut or feces of patients suffering from ulcerative colitis and colorectal cancer. However, a mechanistic model that explains the connection between H 2 S and ulcerative colitis or colorectal cancer development has not been completely formulated. In this study, we examined the chronic cytotoxicity of sulfide using a microplate assay and genotoxicity using the single-cell gel electrophoresis (SCGE; comet assay) in Chinese hamster ovary (CHO) and HT29-Cl.16E cells. Sulfide showed chronic cytotoxicity in CHO cells with a %C1/2 of 368.57 Mmol/L. Sulfide was not genotoxic in the standard SCGE assay. However, in a modified SCGE assay in which DNA repair was inhibited, a marked genotoxic effect was observed. A sulfide concentration as low as 250 Mmol/L (similar to that found in human colon) caused significant genomic DNA damage. The HT29-Cl.16E colonocyte cell line also exhibited increased genomic DNA damage as a function of Na 2 S concentration when DNA repair was inhibited, although these cells were less sensitive to sulfide than CHO cells. These data indicate that given a predisposing genetic background that compromises DNA repair, H 2 S may lead to genomic instability or the cumulative mutations found in adenomatous polyps leading to colorectal cancer.

show abstract

Section: Resultsmentioning

confidence: 84%

Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Attene‐Ramos¹,

Wagner

Plewa

et al. 2006

Molecular Cancer Research

301

204

View full text Add to dashboard Cite

show abstract

“…Because H 2 S concentrations in excess of 1,000 ppm have been measured in gas samples obtained from the rat cecum (59), and H 2 S can readily cross membrane barriers, a detoxification pathway must exist. Whereas Levitt and colleagues (34) suggested a sulfide oxidase of unknown molecular identity, Picton and colleagues (53) suggested that thiosulfate sulfurtransferase (TST), or rhodanese, was the major enzymatic-degradation pathway. Since its discovery, rhodanese, expressed by the liver, has been known as the enzyme responsible for cyanide detoxification.…”

Section: General Interdisciplinary View Of the Inactivation Of H 2 Smentioning

confidence: 99%

Endogenous Production of H₂S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Linden

Levitt

Farrugia

et al. 2010

Antioxidants & Redox Signaling

102

View full text Add to dashboard Cite

Hydrogen sulfide (H 2 S) has long been associated with the gastrointestinal tract, especially the bacteria-derived H 2 S present in flatus. Along with evidence from other organ systems, the finding that gastrointestinal tissues are capable of endogenous production of H 2 S has led to the hypothesis that H 2 S is an endogenous gaseous signaling molecule. In this review, the criteria of gasotransmitters are reexamined, and evidence from the literature regarding H 2 S as a gaseous signaling molecule is discussed. H 2 S is produced enzymatically by gastrointestinal tissues, but evidence is lacking on whether H 2 S production is regulated. H 2 S causes well-defined physiologic effects in gastrointestinal tissues, but evidence for a receptor for H 2 S is lacking. H 2 S is inactivated through enzymatic oxidation, but evidence is lacking on whether manipulating H 2 S oxidation alters endogenous cell signaling. Remaining questions regarding the role of H 2 S as a gaseous signaling molecule in the gastrointestinal tract suggest that H 2 S currently remains a molecule in search of a physiologic function. Antioxid. Redox Signal. 12, 1135-1146.

show abstract

“…We recently showed that colonic mucosal rhodanese can detoxify hydrogen sulfide (15) and thus might protect against mucosal injury. Rhodanese is a mitochondrial enzyme, present in all living organisms from bacteria to humans, and is thought to play a central role in cyanide detoxification (12,28,29).…”

mentioning

confidence: 99%

Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation

Ramasamy¹,

Singh²,

Taniere³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

143

View full text Add to dashboard Cite

Ramasamy, S., S. Singh, P. Taniere, M. J. S. Langman, and M. C. Eggo. Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation. Am J Physiol Gastrointest Liver Physiol 291: G288 -G296, 2006. First published February 23, 2006 doi:10.1152/ajpgi.00324.2005.-H 2S is highly toxic and selectively inhibits butyrate oxidation in colonocytes. Ineffective detoxification may result in mucosal insult, inflammation, and ultimately in colorectal cancer (CRC). Rhodanese can detoxify H 2S and is comprised of two isoenzymes: thiosulfate sulfurtransferase (TST) and mercaptopyruvate sulfurtransferase (MST). Using specific antisera to discriminate TST from MST, we found that only TST could detoxify H2S. In sections of normal colon, both enzymes were located on the luminal mucosal surface, and they were expressed in the colonocytes but not in the mucin-secreting goblet cells. Expression of both enzymes was focally lost in ulcerative colitis and markedly reduced in advanced colon cancer, the disease progression correlating with the decreased expression of MST and TST. In HT-29 cells, a human colon cancer cell line, TST activity and expression were significantly increased by butyrate and by histone deacetylase inhibition, agents that promote HT-29 cell differentiation. Sulfide (0.1 mM) also increased TST activity, but higher sulfide concentrations (0.3-3 mM) were toxic. Preincubation in butyrate to increase TST expression, decreased sensitivity of the cells to sulfide toxicity. We conclude that decreased expression of TST (or MST) is a tumor marker for CRC. TST expression is increased in colonocyte differentiation. Dysregulation of TST expression and activity resulting in inability to effectively detoxify could be a factor in the cell loss and inflammation that accompany ulcerative colitis and ultimately then in CRC. colorectal cancer; thiosulfate sulfurtransferase; butyrate; HT-29 IN THE HUMAN COLON, anaerobic bacteria produce hydrogen sulfide (H 2 S) (25), which inhibits the oxidation of short-chain fatty acids (SCFA) (18,19). SCFAs are the main energy source (Ͼ70% ) for colonocytes (18) and also contribute 5-10% of the total energy supplies in humans. Inhibition of their oxidation in the colon will result in colonocyte starvation and death, resulting in inflammation. This, the "energy deficiency" hypothesis of Roediger (18), is postulated to lead to ulcerative colitis (UC). Many studies have shown that patients with UC have increased colorectal cancer (CRC) risk, with Prior et al. (16) estimating this as an 11-fold excess. On the basis of these studies, we suggest that the expression of enzymes important in sulfide detoxification is essential to preserve a healthy mucosa and that derangements in expression may accompany UC and CRC.We recently showed that colonic mucosal rhodanese can detoxify hydrogen sulfide (15) and thus might protect against mucosal injury. Rhodanese is a mitochondrial enzyme, present in all living organisms from bacteria to humans, and is thought to play a cen...

show abstract

Mucosal protection against sulphide: importance of the enzyme rhodanese

Cited by 103 publications

References 19 publications

Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Endogenous Production of H₂S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation

Contact Info

Product

Resources

About

Mucosal protection against sulphide: importance of the enzyme rhodanese

Cited by 103 publications

References 19 publications

Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Endogenous Production of H2S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation

Contact Info

Product

Resources

About

Endogenous Production of H₂S in the Gastrointestinal Tract: Still in Search of a Physiologic Function