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Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
Dextran sulfate sodium inhibits alanine synthesis in Caco-2 cells
Zhong Ye1, Darya O Mishchuk, Natasha S Stephens
1Department of Nutrition, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA;
Abstract:
To understand and characterize the pathogenic mechanisms of inflammatory bowel disease, dextran sulfate sodium (DSS) has been used to induce acute and chronic colitis in animal models by causing intestinal epithelium damage. The mechanism of action of DSS in producing this outcome is not well understood. In an effort to understand how DSS might impact epithelial cell metabolism, we studied the intestinal epithelial cell line Caco-2 incubated with 1% DSS over 56 hours using (1)H NMR spectroscopy. We observed no difference in cell viability as compared to control cultures, and an approximately 1.5-fold increase in IL-6 production upon incubation with 1% DSS. The effect on Caco-2 cell metabolism as measured through changes in the concentration of metabolites in the cell supernatant included a three-fold decrease in the concentration of alanine. Given that the concentrations of other amino acids in the cell culture supernatant were not different between treated and control cultures over 56 hours suggest that DSS inhibits alanine synthesis, specifically alanine aminotransferase, without affecting other key metabolic pathways. The importance of alanine aminotransferase in inflammatory bowel disease is discussed.
Insights
Dextran sulfate sodium (DSS) induces colitis by damaging the intestinal epithelium. This study reveals DSS specifically inhibits alanine synthesis via alanine aminotransferase in Caco-2 cells, impacting inflammatory bowel disease pathogenesis.
Area of Science:
- Gastroenterology
- Cell Biology
- Metabolomics
Background:
- Inflammatory bowel disease (IBD) pathogenesis involves intestinal epithelial damage.
- Dextran sulfate sodium (DSS) is a common inducer of colitis in animal models.
- The precise mechanisms by which DSS affects epithelial cell metabolism remain unclear.
Purpose of the Study:
- To investigate the impact of DSS on the metabolism of intestinal epithelial cells.
- To elucidate the specific metabolic pathways affected by DSS exposure.
Main Methods:
- Utilized the Caco-2 intestinal epithelial cell line.
- Incubated cells with 1% DSS for 56 hours.
- Analyzed cell supernatant metabolites using 1H NMR spectroscopy.
Main Results:
- No significant difference in cell viability was observed between DSS-treated and control groups.
- DSS treatment led to a 1.5-fold increase in IL-6 production.
- A three-fold decrease in alanine concentration was detected in the DSS-treated cell supernatant, while other amino acids remained unchanged.
Conclusions:
- DSS selectively inhibits alanine synthesis, likely by targeting alanine aminotransferase.
- This specific metabolic disruption may contribute to the pathogenic mechanisms of DSS-induced colitis.
- Understanding DSS's effect on alanine aminotransferase is crucial for IBD research.
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