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NADPH oxidase is involved in polychlorinated biphenyl‐mediated alterations of tight junction proteins in cells of the gastrointestinal tract
Author(s) -
Choi Yean Jung,
Eum Sung Yong,
Son Heejeong,
Hennig Bernhard,
Toborek Michal
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.570.7
Subject(s) - tight junction , occludin , paracellular transport , microbiology and biotechnology , nadph oxidase , caco 2 , chemistry , cell junction , claudin , epithelium , biochemistry , in vitro , biology , permeability (electromagnetism) , cell , reactive oxygen species , membrane , genetics
Exposure to polychlorinated biphenyls (PCBs) can contribute to numerous disease states. The main route of exposure to PCBs is through the gastrointestinal tract; however, little is known about the effects of PCBs on intestinal epithelial barrier functions. In the present study, we evaluated the effects of several highly‐chlorinated PCBs using human intestinal Caco‐2 cell line as an in vitro epithelial model system. Epithelial cells are comprised of tight junction (TJ) proteins that form an intricate assembly of membrane, cytoplasmic and accessory proteins linked to an actin cytoskeleton and which contribute to limited paracellular diffusion between adjacent epithelium. We demonstrated that exposure to PCBs increased permeability of FITC‐labeled dextran (4 kDa) across Caco‐2 monolayers. Consistent with permeability results, PCB disrupted expression of TJ proteins occludin and ZO‐1. These effects were associated with upregulation of the expressions of NADPH oxidase subunits as detected by immunoblotting. In addition, inhibition of NAPDH oxidase by apocynin significantly blocked PCB‐mediated increase in epithelial permeability and alterations of TJ protein expression. Similar effects were exerted by pretreatment with Rho kinase and Ras inhibitors suggesting that PCBs can disrupt epithelial barrier integrity through induction of redox‐regulated mechanisms. Supported by NIH/NIEHS (P42 ES 07380).