Disruption of epithelial barrier function by H2O2: distinct responses of Caco-2 and Madin-Darby canine kidney (MDCK) strains.
Modulation of epithelial function by oxidants such as hydrogen peroxide may contribute to a variety of disease processes. The effects of hydrogen peroxide (H2O2) on epithelial barrier function and tight junction protein distribution were compared in three distinct types of polarised epithelial cell, each of which was found to respond differently to H2O2. Of the cell-lines examined, Madin-Darby canine kidney (MDCK) stain II was the most susceptible to H2O2 and Caco-2 the least H2O2 induced a decrease in transepithelial electrical resistance in all three epithelial cell-lines which was accompanied by redistribution of the tight junction protein occludin in Caco-2 and MDCK II but not MDCK I, cell layers. The effects of H2O2 on epithelia displayed marked asymmetry, each cell-line being affected more by basal than apical application of H2O2. Genistein partially prevented the effects of H2O2 on Caco-2 cells suggesting a role for protein tyrosine phosphorylation in H2O2-induced epithelial barrier dysfunction. However, genistein was without effect on the responses of MDCK cells to H2O2. Taken together these data indicate that H2O2 has distinct effects onthe tight junctions of epithelial cells from different origins and suggest that enhanced tyrosine phosphorylation is a contributory factor inthe enhanced permeability of some, but possibly not all, epithelial cell-lines.
Jepson
M A
MA
Cell Imaging Facility and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. m.a.jepson@bris.ac.uk
D000818:Animals; D018938:Caco-2 Cells; D004285:Dogs; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D007422:Intestines / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D008565:Membrane Proteins / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D010750:Phosphoproteins / Q000187:drug effects; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D016877:Oxidants; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D006861:Hydrogen Peroxide