Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF andl -glutamine
| Autor: | Parimal Sheth, Radhakrishna Rao, C. M. Mansbach, Shyamali Basuroy |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Colon Physiology Glutamine Metabolite Detergents Acetaldehyde In Vitro Techniques Biology Cell junction Tight Junctions Adherens junction chemistry.chemical_compound Epidermal growth factor Physiology (medical) Humans Drug Interactions Intestinal Mucosa Phosphorylation Ethanol Epidermal Growth Factor Hepatology Tight junction Gastroenterology Adherens Junctions Cell biology Solubility chemistry Biochemistry Tyrosine Female |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 289:G367-G375 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00464.2004 |
| Popis: | Acetaldehyde, a toxic metabolite of ethanol oxidation, is suggested to play a role in the increased risk for gastrointestinal cancers in alcoholics. In the present study, the effect of acetaldehyde on tyrosine phosphorylation, immmunofluorescence localization, and detergent-insoluble fractions of the tight junction and the adherens junction proteins was determined in the human colonic mucosa. The role of EGF and l-glutamine in prevention of acetaldehyde-induced effects was also evaluated. Acetaldehyde reduced the protein tyrosine phosphatase activity, thereby increasing the tyrosine phosphorylation of occludin, E-cadherin, and β-catenin. The levels of occludin, zonula occludens-1, E-cadherin, and β-catenin in detergent-insoluble fractions were reduced by acetaldehyde, while it increased their levels in detergent-soluble fractions. Pretreatment with EGF or l-glutamine prevented acetaldehyde-induced protein tyrosine phosphorylation, redistribution from intercellular junctions, and reduction in the levels of detergent-insoluble fractions of occludin, zonula occludens-1, E-cadherin, and β-catenin. These results demonstrate that acetaldehyde induces tyrosine phosphorylation and disrupts tight junction and adherens junction in human colonic mucosa, which can be prevented by EGF and glutamine. |
| Databáze: | OpenAIRE |
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