L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer.
Role of L-glutamine in the protection of intestinal epithelium from acetaldehyde-induced disruption of barrier function was evaluated in Caco-2 cell monolayer. L-Glutamine reduced the acetaldehyde-induced decrease in transepithelilal electrical resistance and increase in permeability to inulin and lipopolysaccharide in a time- and dose-dependent manner; d-glutamine, L-aspargine, L-arginine, L-lysine, or L-alanine produced no significant protection. The glutaminase inhibitor 6-diazo-5-oxo-L-norleucine failed to affect the L-glutamine-mediated protection of barrier function. L-Glutamine reduced the acetaldehyde-induced redistribution of occludin, zonula occludens-1 (ZO-1), E-cadherin, and beta-catenin from the intercellular junctions. Acetaldehyde dissociates occludin, ZO-1, E-cadherin, and beta-catenin from the actin cytoskeleton, and this effect was reduced by L-glutamine. L-Glutamine induced a rapid increase in the tyrosine phosphorylation of EGF receptor, and the protective effect of L-glutamine was prevented by AG1478, the EGF-receptor tyrosine kinase inhibitor. These results indicate that L-glutamine prevents acetaldehyde-induced disruption of the tight junction and increase in the paracellular permeability in Caco-2 cell monolayer by an EGF receptor-dependent mechanism.
Seth
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Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Basuroy
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Sheth
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Rao
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D000079:Acetaldehyde / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000187:drug effects; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010766:Phosphorylation; D011799:Quinazolines; D019108:Tight Junctions / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D000199:Actins; D003598:Cytoskeletal Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D011799:Quinazolines; D020032:Tyrphostins; D005973:Glutamine; C101044:RTKI cpd; D008353:Mannitol; D014443:Tyrosine; D004533:Egtazic Acid; D066246:ErbB Receptors; D000079:Acetaldehyde