Wip1 protects hydrogen peroxide-induced colonic epithelial barrier dysfunction |
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Authors: | T Oshima M Sasaki H Kataoka H Miwa T Takeuchi T Joh |
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Institution: | (1) Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan;(2) Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan;(3) Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi 371-8512, Japan |
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Abstract: | Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as
mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains
unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated
protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical
TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and
oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection.
This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal
permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.
Received 14 June 2007; received after revision 8 October 2007; accepted 8 October 2007 |
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Keywords: | Tight junction Wip1 p38 MAP kinase permeability claudin-4 |
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