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Am J Physiol Gastrointest Liver Physiol (February 17, 2005). doi:10.1152/ajpgi.00464.2004
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Submitted on October 15, 2004
Accepted on February 12, 2005

Acetaldehyde Disrupts Tight Junctions and Adherens Junctions in Human Colonic Mucosa: Protection by EGF and L-Glutamine

S. Basuroy1, P. Sheth1, C. Mansbach1, and R. K. Rao1*

1 Department of Physiology and Medicine, University of Tennessee Health Science Center, Memphis, TN, USA; The Veterans Affairs Medical Center, Memphis, TN, USA

* To whom correspondence should be addressed. E-mail: rkrao{at}physio1.utmem.edu.

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 {beta}-catenin. The levels of occludin, ZO-1, E-cadherin and {beta}-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, ZO-1, E-cadherin and {beta}-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.




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