Journal of Cell Science, Vol 112, Issue 23 4347-4356, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition

M Wachtel, K Frei, E Ehler, A Fontana, K Winterhalter and SM Gloor
Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Zentrum, CH-8092 Zurich, Switzerland.

Regulation of epithelial and endothelial permeability is essential for proper function of compartmentalized organisms, and tyrosine phosphorylation plays an important role in this process. We analyzed the impact of protein tyrosine phosphatase (PTP) inhibition on the structure of endothelial junctional proteins. In human umbilical vein endothelial cells (HUVECs) the PTP inhibitors phenylarsine oxide (PAO) and pervanadate induced proteolysis of the tight junction protein occludin. Occludin proteolysis was inhibited by the metalloproteinase inhibitor 1,10-phenanthroline (PHEN), but not by inhibitors against other types of proteases. The junctional proteins ZO-1, cadherin and beta-catenin were not cleaved. Under conditions of occludin proteolysis, PAO treatment elevated permeability for FITC-dextran. Simultaneous incubation of HUVECs with PAO and PHEN inhibited the rise in permeability by more than 60%. PAO treatment lead to progressive disappearance of occludin from the cell periphery. In contrast, ZO-1, cadherin and beta-catenin retained their positions at the sites of intercellular contact. Simultaneous administration of PAO and PHEN greatly prevented the redistribution of occludin. These results demonstrate a selective cleavage of occludin by a metalloproteinase and suggest that this process can contribute to the control of paracellular permeability in endothelial cells.

This article has been cited by other articles:

				J. D. Kawedia, M. Jiang, A. Kulkarni, H. E. Waechter, K. S. Matlin, G. M. Pauletti, and A. G. Menon The Protein Kinase A Pathway Contributes to Hg2+-Induced Alterations in Phosphorylation and Subcellular Distribution of Occludin Associated with Increased Tight Junction Permeability of Salivary Epithelial Cell Monolayers J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 829 - 837. [Abstract] [Full Text] [PDF]

				D. Navaratna, G. Menicucci, J. Maestas, R. Srinivasan, P. McGuire, and A. Das A peptide inhibitor of the urokinase/urokinase receptor system inhibits alteration of the blood-retinal barrier in diabetes FASEB J, September 1, 2008; 22(9): 3310 - 3317. [Abstract] [Full Text] [PDF]

				R. Amstutz, M. Wachtel, H. Troxler, P. Kleinert, M. Ebauer, T. Haneke, C. Oehler-Janne, D. Fabbro, F. K. Niggli, and B. W. Schafer Phosphorylation Regulates Transcriptional Activity of PAX3/FKHR and Reveals Novel Therapeutic Possibilities Cancer Res., May 15, 2008; 68(10): 3767 - 3776. [Abstract] [Full Text] [PDF]

				M. Yamamoto, S. H. Ramirez, S. Sato, T. Kiyota, R. L. Cerny, K. Kaibuchi, Y. Persidsky, and T. Ikezu Phosphorylation of Claudin-5 and Occludin by Rho Kinase in Brain Endothelial Cells Am. J. Pathol., February 1, 2008; 172(2): 521 - 533. [Abstract] [Full Text] [PDF]

				K. Wosik, R. Cayrol, A. Dodelet-Devillers, F. Berthelet, M. Bernard, R. Moumdjian, A. Bouthillier, T. L. Reudelhuber, and A. Prat Angiotensin II Controls Occludin Function and Is Required for Blood Brain Barrier Maintenance: Relevance to Multiple Sclerosis J. Neurosci., August 22, 2007; 27(34): 9032 - 9042. [Abstract] [Full Text] [PDF]

				A. Reijerkerk, G. Kooij, S. M. A. van der Pol, S. Khazen, C. D. Dijkstra, and H. E. de Vries Diapedesis of monocytes is associated with MMP-mediated occludin disappearance in brain endothelial cells FASEB J, December 1, 2006; 20(14): 2550 - 2552. [Abstract] [Full Text] [PDF]

				L. DeMaio, M. Rouhanizadeh, S. Reddy, A. Sevanian, J. Hwang, and T. K. Hsiai Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H674 - H683. [Abstract] [Full Text] [PDF]

				N. T. Collins, P. M. Cummins, O. C. Colgan, G. Ferguson, Y. A. Birney, R. P. Murphy, G. Meade, and P. A. Cahill Cyclic Strain-Mediated Regulation of Vascular Endothelial Occludin and ZO-1: Influence on Intercellular Tight Junction Assembly and Function Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 62 - 68. [Abstract] [Full Text] [PDF]

				B. T. Hawkins and T. P. Davis The Blood-Brain Barrier/Neurovascular Unit in Health and Disease Pharmacol. Rev., June 1, 2005; 57(2): 173 - 185. [Abstract] [Full Text] [PDF]

				S. C. Pflugfelder, W. Farley, L. Luo, L. Z. Chen, C. S. de Paiva, L. C. Olmos, D.-Q. Li, and M. E. Fini Matrix Metalloproteinase-9 Knockout Confers Resistance to Corneal Epithelial Barrier Disruption in Experimental Dry Eye Am. J. Pathol., January 1, 2005; 166(1): 61 - 71. [Abstract] [Full Text] [PDF]

				C. Bojarski, J. Weiske, T. Schoneberg, W. Schroder, J. Mankertz, J.-D. Schulzke, P. Florian, M. Fromm, R. Tauber, and O. Huber The specific fates of tight junction proteins in apoptotic epithelial cells J. Cell Sci., April 15, 2004; 117(10): 2097 - 2107. [Abstract] [Full Text] [PDF]

				K. A. Witt, K. S. Mark, S. Hom, and T. P. Davis Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2820 - H2831. [Abstract] [Full Text] [PDF]

				S. H. M. Chen, M. F. Stins, S.-H. Huang, Y. H. Chen, K. J. Kwon-Chung, Y. Chang, K. S. Kim, K. Suzuki, and A. Y. Jong Cryptococcus neoformans induces alterations in the cytoskeleton of human brain microvascular endothelial cells J. Med. Microbiol., November 1, 2003; 52(11): 961 - 970. [Abstract] [Full Text] [PDF]

				R. H. Adamson, M. Zeng, G. N. Adamson, J. F. Lenz, and F. E. Curry PAF- and bradykinin-induced hyperpermeability of rat venules is independent of actin-myosin contraction Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H406 - H417. [Abstract] [Full Text] [PDF]

				J. D. Huber, V. S. Hau, L. Borg, C. R. Campos, R. D. Egleton, and T. P. Davis Blood-brain barrier tight junctions are altered during a 72-h exposure to lambda -carrageenan-induced inflammatory pain Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1531 - H1537. [Abstract] [Full Text] [PDF]

				M. Asahi, X. Wang, T. Mori, T. Sumii, J.-C. Jung, M. A. Moskowitz, M. E. Fini, and E. H. Lo Effects of Matrix Metalloproteinase-9 Gene Knock-Out on the Proteolysis of Blood-Brain Barrier and White Matter Components after Cerebral Ischemia J. Neurosci., October 1, 2001; 21(19): 7724 - 7732. [Abstract] [Full Text] [PDF]

				H. Lum and K. A. Roebuck Oxidant stress and endothelial cell dysfunction Am J Physiol Cell Physiol, April 1, 2001; 280(4): C719 - C741. [Abstract] [Full Text] [PDF]

				J. D. Huber, K. A. Witt, S. Hom, R. D. Egleton, K. S. Mark, and T. P. Davis Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1241 - H1248. [Abstract] [Full Text] [PDF]

				J. Longin, P. Guillaumot, M.-A. Chauvin, A.-M. Morera, and B. Le Magueresse-Battistoni MT1-MMP in rat testicular development and the control of Sertoli cell proMMP-2 activation J. Cell Sci., January 6, 2001; 114(11): 2125 - 2134. [Abstract] [Full Text] [PDF]