Nitric oxide attenuates hydrogen peroxide-induced barrier disruption and protein tyrosine phosphorylation in monolayers of intestinal epithelial cell.
The intestinal epithelium provides a barrier to the transport of harmful luminal molecules into the systemic circulation. A dysfunctional epithelial barrier is closely associated with the pathogenesis of a variety of intestinal and systemic disorders. We investigated here the effects of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) on the barrier function of a human intestinal epithelial cell line, Caco-2. When treated with H(2)O(2), Caco-2 cell monolayers grown on permeable supports exhibited several remarkable features of barrier dysfunction as follows: a decrease in transepithelial electrical resistance, an increase in paracellular permeability to dextran, and a disruption of the intercellular junctional localization of the scaffolding protein ZO-1. In addition, an induction of tyrosine phosphorylation of numerous cellular proteins including ZO-1, E-cadherin, and beta-catenin, components of tight and adherens junctions, was observed. On the other hand, combined treatment of Caco-2 monolayers with H(2)O(2) and an NO donor (NOC5 or NOC12) relieved the damage to the barrier function and suppressed the protein tyrosine phosphorylation induced by H(2)O(2) alone. These results suggest that NO protects the barrier function of intestinal epithelia from oxidative stress by modulating some intracellular signaling pathways of protein tyrosine phosphorylation in epithelial cells.
Katsube
Takanori
T
Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba-shi, Chiba 263-8555, Japan. tkatsu@nirs.go.jp
Tsuji
Hideo
H
Onoda
Makoto
M
D022005:Adherens Junctions / Q000378:metabolism* / Q000473:pathology; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007410:Intestinal Diseases / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009603:Nitroso Compounds / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000378:metabolism
C513644:3-(2-hydroxy-1-(1-methylethyl-2-nitrosohydrazino)-1-propanamine); D015820:Cadherins; D006834:Hydrazines; D008565:Membrane Proteins; C118603:NOC 12; D009603:Nitroso Compounds; D016877:Oxidants; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D009569:Nitric Oxide; D014443:Tyrosine; D006861:Hydrogen Peroxide