Detoxification of H(2)S by differentiated colonic epithelial cells: implication of the sulfide oxidizing unit and of the cell respiratory capacity

Antioxid Redox Signal. 2012 Jul 1;17(1):1-10. doi: 10.1089/ars.2011.4186. Epub 2012 Apr 17.

Abstract

Aims: Sulfide is released in the large intestine lumen by the microbiota and is an inhibitor of mitochondrial respiration and a genotoxic agent in colonocytes when present in excess. Deciphering how colonocytes metabolize sulfide is an important issue.

Results: In this study, using the human colonic epithelial HT-29 Glc(-/+) cells, we found that 50 μM sodium hydrogen sulfide represents the threshold of concentration above which respiration is decreased. The capacity of HT-29 Glc(-/+) cells to oxidize lower concentration of sulfide was associated with the expression of transcripts corresponding to the enzymes of the sulfide oxidizing unit (SOU), that is, sulfide quinone reductase (SQR), dioxygenase ethylmalonic encephalopathy, and thiosulfate sulfur transferase (TST). Inhibition of cell O(2) consumption by sulfide was reverted by zinc but not by calcium and iron. When the cells undergo either spontaneous or butyrate-induced differentiation, their capacity to oxidize sulfide was significantly increased. The expression levels of the genes corresponding to the enzymes of the SOU were not increased, whereas increased cellular maximal respiratory capacity and oxygen consumption by the dioxygenase were both measured. In human biopsies recovered from various parts of the large intestine, the three enzymes of the SOU were expressed.

Innovation: SOU and cell respiratory capacity are crucial for sulfide detoxification in colonocytes.

Conclusion: Sulfide oxidative capacity in the colonic mucosa is higher in differentiated than in proliferative epithelial cells. The cell respiratory capacity and SOU activity appear to represent major determinants allowing sulfide detoxification in colonic epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Respiration / drug effects*
  • Colon
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • HT29 Cells
  • Humans
  • Hydrogen Sulfide / metabolism
  • Hydrogen Sulfide / pharmacology*
  • Quinone Reductases / metabolism
  • Sulfides / metabolism*
  • Thiosulfate Sulfurtransferase / metabolism

Substances

  • Sulfides
  • Quinone Reductases
  • sulfide quinone reductase
  • Thiosulfate Sulfurtransferase
  • Hydrogen Sulfide