Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine

被引:104
作者
Basuroy, S
Sheth, P
Mansbach, CM
Rao, RK [1 ]
机构
[1] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA
[2] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA
[3] Vet Affairs Med Ctr, Memphis, TN USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2005年 / 289卷 / 02期
关键词
alcohol; barrier function; human colon; epidermal growth factor;
D O I
10.1152/ajpgi.00464.2004
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine. Am J Physiol Gastrointest Liver Physiol 289: G367-G375, 2005. First published February 17, 2005; doi:10.1152/ajpgi.00464.2004.-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 detergentsoluble 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.
引用
收藏
页码:G367 / G375
页数:9
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