Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine.
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, immunofluorescence 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, zonula occludens-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, zonula occludens-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.
Basuroy
S
S
Dept. of Physiology, University of Tennessee, 894 Union Avenue, Memphis, TN 38163, USA.
Sheth
P
P
Mansbach
C M
CM
Rao
R K
RK
D000079:Acetaldehyde / Q000494:pharmacology*; D022005:Adherens Junctions / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects; D003902:Detergents; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D012995:Solubility; D019108:Tight Junctions / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D003902:Detergents; D005973:Glutamine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D000079:Acetaldehyde