| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, Johns Hopkins University, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: vnataraj{at}jhmi.edu.
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, 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 permeability changes, BPAECs were transfected with vector or FAK wild type or FAK-related non-kinase (FRNK) plasmids. Overexpression of FRNK reduced FAK expression, 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 towards 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 vascular endothelial barrier function regulated by cell-cell and cell-matrix contacts.
This article has been cited by other articles:
|
|
 |
|
  A. Dossumbekova, E. V. Berdyshev, I. Gorshkova, Z. Shao, C. Li, P. Long, A. Joshi, V. Natarajan, and T. L. Vanden Hoek Akt activates NOS3 and separately restores barrier integrity in H2O2-stressed human cardiac microvascular endothelium Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2417 - H2426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Desai, S. E. Sinclair, K. E. Chapman, A. Hassid, and C. M. Waters High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L769 - L778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Reutershan, R. Stockton, A. Zarbock, G. W. Sullivan, D. Chang, D. Scott, M. A. Schwartz, and K. Ley Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration Am. J. Respir. Crit. Care Med., May 15, 2007; 175(10): 1027 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Moldovan, K. Mythreye, P. J. Goldschmidt-Clermont, and L. L. Satterwhite Reactive oxygen species in vascular endothelial cell motility. Roles of NAD(P)H oxidase and Rac1 Cardiovasc Res, July 15, 2006; 71(2): 236 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Moldobaeva, L. E. Welsh-Servinsky, L. A. Shimoda, R. S. Stephens, A. D. Verin, R. M. Tuder, and D. B. Pearse Role of protein kinase G in barrier-protective effects of cGMP in human pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L919 - L930. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
