期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 289, 期 6, 页码 L999-L1010出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00211.2005
关键词
focal adhesion kinase-related non-kinase; vascular endothelial-cadherin; beta-catenin; hydrogen peroxide; transendothelial electrical resistance
资金
- NHLBI NIH HHS [R01 HL 69909, P01 HL 58064] Funding Source: Medline
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, beta-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, beta-catenin, and VE-cadherin and cell-cell adhesion. Additionally, FRNK prevented H2O2-induced distribution of FAK, paxillin, beta-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.
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