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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/L999    most recent 00211.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Usatyuk, P. V. Articles by Natarajan, V. Search for Related Content PubMed PubMed Citation Articles by Usatyuk, P. V. Articles by Natarajan, V.

Regulation of reactive oxygen species-induced endothelial cell-cell and cell-matrix contacts by focal adhesion kinase and adherens junction proteins

Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois

Submitted 10 May 2005 ; accepted in final form 18 July 2005

Oxidants, generated by activated neutrophils, have been implicated in the pathophysiology of vascular disorders and lung injury; however, mechanisms of oxidant-mediated endothelial barrier dysfunction are unclear. Here, we have investigated the role of focal adhesion kinase (FAK) in regulating hydrogen peroxide (H₂O₂)-mediated tyrosine phosphorylation of intercellular adhesion proteins and barrier function in endothelium. Treatment of bovine pulmonary artery endothelial cells (BPAECs) with H₂O₂ increased tyrosine phosphorylation of FAK, paxillin, -catenin, and vascular endothelial (VE)-cadherin and decreased transendothelial electrical resistance (TER), an index of cell-cell adhesion and/or cell-matrix adhesion. To study the role of FAK in H₂O₂-induced TER changes, BPAECs were transfected with vector or FAK wild-type or FAK-related non-kinase (FRNK) plasmids. Overexpression of FRNK reduced FAK expression and attenuated H₂O₂-mediated tyrosine phosphorylation of FAK, paxillin, -catenin, and VE-cadherin and cell-cell adhesion. Additionally, FRNK prevented H₂O₂-induced distribution of FAK, paxillin, -catenin, or VE-cadherin toward focal adhesions and cell-cell adhesions but not actin stress fiber formation. These results suggest that activation of FAK by H₂O₂ is an important event in oxidant-mediated VE barrier function regulated by cell-cell and cell-matrix contacts.

focal adhesion kinase-related non-kinase; vascular endothelial-cadherin; -catenin; hydrogen peroxide; transendothelial electrical resistance

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