| Molecular mechanisms regulating dissociation of cell-cell junction of epithelial cells by oxidative stress. | |
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MedLine Citation:
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PMID: 19422420 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidative stress is regarded as a causative factor in aging and various degenerative diseases. Here, we show the mechanism by which oxidative stress induces disruption of cell-cell junctions using retinal pigment epithelial cells. We demonstrated that reactive oxygen species (ROS)-mediated activation of Src kinase increases the tyrosine phosphorylation state of p120-catenin and rapidly triggers translocation of p120-catenin and internalization of N-cadherin from the cell-cell adhesion sites to an early endosomal compartment. Endosomal accumulation of p120-catenin resulted in stress fiber formation and cell-cell dissociation through the activation of Rho/Rho kinase pathway. However, these cytoskeletal remodeling and cell-cell dissociation induced by oxidative stress were transient, due to the activation of nuclear factor-kappaB (NF-kappaB) and the expression of manganese superoxide dismutase (Mn-SOD). Using the NF-kappaB specific inhibitor DHMEQ, we found that NF-kappaB is part of a negative feedback loop to control intracellular ROS levels. Finally, we demonstrated that H(2)O(2) treatment alone does not induce the epithelial mesenchymal transition (EMT) in retinal pigment epithelial cells, which can be induced by TNF-alpha treatment. These findings suggest that oxidative stress is a crucial factor to induce the cell-cell dissociation, an initial step of EMT, but does not provide sufficient signals to establish and to maintain the EMT. |
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Authors:
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Junko Inumaru; Osamu Nagano; Eri Takahashi; Takatsugu Ishimoto; Satoshi Nakamura; Yoshimi Suzuki; Shin-Ichiro Niwa; Kazuo Umezawa; Hidenobu Tanihara; Hideyuki Saya |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-30 |
Journal Detail:
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Title: Genes to cells : devoted to molecular & cellular mechanisms Volume: 14 ISSN: 1365-2443 ISO Abbreviation: Genes Cells Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-09-18 Completed Date: 2009-12-11 Revised Date: 2010-01-29 |
Medline Journal Info:
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Nlm Unique ID: 9607379 Medline TA: Genes Cells Country: England |
Other Details:
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Languages: eng Pagination: 703-16 Citation Subset: IM |
Affiliation:
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Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Adhesion Molecules
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genetics,
metabolism Cell Differentiation Epithelial Cells / cytology, drug effects*, metabolism Humans Hydrogen Peroxide / pharmacology* Intercellular Junctions / drug effects* Mesoderm / cytology, metabolism NF-kappa B / genetics, metabolism Oxidative Stress* Phosphoproteins / genetics, metabolism Reactive Oxygen Species / metabolism, pharmacology Retinal Pigment Epithelium / cytology*, drug effects Superoxide Dismutase / genetics, metabolism rho-Associated Kinases / genetics, metabolism src-Family Kinases / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cell Adhesion Molecules; 0/NF-kappa B; 0/Phosphoproteins; 0/Reactive Oxygen Species; 0/delta catenin; 7722-84-1/Hydrogen Peroxide; EC 1.15.1.1/Superoxide Dismutase; EC 2.7.10.2/src-Family Kinases; EC 2.7.11.1/rho-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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