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Review
. 2009 Aug;50(2):638-44.
doi: 10.1002/hep.23009.

Endotoxemia and gut barrier dysfunction in alcoholic liver disease

Radhakrishna Rao  1
Affiliations
Review

Endotoxemia and gut barrier dysfunction in alcoholic liver disease

Radhakrishna Rao. Hepatology. 2009 Aug.
No abstract available

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Figures

Fig. 1:
Fig. 1:
Diagrammatic representation of ethanol-induced intestinal permeability and endotoxemia. Ethanol in colonic lumen is metabolized to acetaldehyde by microflora and mucosa. Acetaldehyde disrupts epithelial barrier function and allows diffusion of bacterial lipopolysaccharide (LPS) into portal circulation. In the liver, LPS activates kupffer cells via LPB/CD14/TLR-4-dependent mechanism
Fig. 2:
Fig. 2:. Diagrammatic model showing acetaldehyde-induced loss of interaction between PTP1B-E-cadherin-β-catenin.
Cadherin-based cell-cell adhesion is mediated by interaction of E-cadherin with β-catenin. PTP1B binds to intracellular domain of E-cadherin and dephosphorylates β-catenin on Tyr residues. Treatment of cell monolayers with acetaldehyde induces inhibition and dissociation of PTP1B from E-cadherin (1), which results in increased Tyr-phosphorylation of β-catenin and E-cadherin (2). Tyr-phosphorylation of β-catenin results in the loss of its interaction with E-cadherin (3), and loss of interaction between E-cadherin and β-catenin leads to a loss of homophilic interaction between extracellular domains of E-cadherin and disruption of adherens junction(4). Disrption fof adherens junctions leads to disruption of tight junctions (5). Ethanol at high doses alters cytoskeletal structure by nitric oxide and MLCK-dependent mechanism (6), which in turn disrupts tight junctions (7).
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