© 2000 American Heart Association, Inc.
Molecular Medicine |
Activation of RhoA by Thrombin in Endothelial Hyperpermeability
Role of Rho Kinase and Protein Tyrosine Kinases
From the Gaubius Laboratory TNO Health and Prevention (G.P.v.N.A., M.A.V., V.W.M.v.H.), Leiden; Division of Cell Biology (S.v.D., J.G.C.), The Netherlands Cancer Institute, Amsterdam; and Institute for Cardiovascular Research (G.P.v.N.A., V.W.M.v.H.), Vrije Universiteit, Amsterdam, the Netherlands.
Correspondence to Prof Dr V.W.M. van Hinsbergh, Gaubius Laboratory TNO-PG, PO Box 2215, 2301 CE Leiden, the Netherlands. E-mail vwm.vanhinsbergh{at}pg.tno.nl
Abstract—Endothelial cells (ECs) actively regulate the extravasation of blood constituents. On stimulation by vasoactive agents and thrombin, ECs change their cytoskeletal architecture and small gaps are formed between neighboring cells. These changes partly depend on a rise in [Ca2+]i and activation of the Ca2+/calmodulin-dependent myosin light chain kinase. In this study, mechanisms that contribute to the thrombin-enhanced endothelial permeability were further investigated. We provide direct evidence that thrombin induces a rapid and transient activation of RhoA in human umbilical vein ECs. Under the same conditions, the activity of the related protein Rac was not affected. This was accompanied by an increase in myosin light chain phosphorylation, the generation of F-actin stress fibers, and a prolonged increase in endothelial permeability. Inhibition of the RhoA target Rho kinase with the specific inhibitor Y-27632 reduced all of these effects markedly. In the presence of Y-27632, the thrombin-enhanced permeability was additionally reduced by chelation of [Ca2+]i by BAPTA. These data indicate that RhoA/Rho kinase and Ca2+ represent 2 pathways that act on endothelial permeability. In addition, the protein tyrosine kinase inhibitor genistein reduced thrombin-induced endothelial permeability without affecting activation of RhoA by thrombin. Our data support a model of thrombin-induced endothelial permeability that is regulated by 3 cellular signal transduction pathways.
Key Words: human endothelial cells • RhoA • protein tyrosine kinases • calcium • phosphorylation
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|
|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
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|
|
|
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|
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|
|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird Thrombin and Phenotypic Modulation of the Endothelium Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 41 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 S. M. Stamatovic, R. F. Keep, S. L. Kunkel, and A. V. Andjelkovic Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase J. Cell Sci., November 15, 2003; 116(22): 4615 - 4628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
|
|
A. V. SOMLYO, C. PHELPS, C. DIPIERRO, M. ETO, P. READ, M. BARRETT, J. J. GIBSON, M. C. BURNITZ, C. MYERS, and A. P. SOMLYO Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants FASEB J, February 1, 2003; 17(2): 223 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
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A. M. J. Buchan, C.-Y. Lin, J. Choi, and D. L. Barber Somatostatin, Acting at Receptor Subtype 1, Inhibits Rho Activity, the Assembly of Actin Stress Fibers, and Cell Migration J. Biol. Chem., August 2, 2002; 277(32): 28431 - 28438. [Abstract] [Full Text] [PDF]
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I. Carton, D. Trouet, D. Hermans, H. Barth, K. Aktories, G. Droogmans, N. K. Jorgensen, E. K. Hoffmann, B. Nilius, and J. Eggermont RhoA exerts a permissive effect on volume-regulated anion channels in vascular endothelial cells Am J Physiol Cell Physiol, July 1, 2002; 283(1): C115 - C125. [Abstract] [Full Text] [PDF]
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 D. L. Cioffi, T. M. Moore, J. Schaack, J. R. Creighton, D. M.F. Cooper, and T. Stevens Dominant regulation of interendothelial cell gap formation by calcium-inhibited type 6 adenylyl cyclase J. Cell Biol., June 24, 2002; 157(7): 1267 - 1278. [Abstract] [Full Text] [PDF]
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V. Vouret-Craviari, C. Bourcier, E. Boulter, and E. Van Obberghen-Schilling Distinct signals via Rho GTPases and Src drive shape changes by thrombin and sphingosine-1-phosphate in endothelial cells J. Cell Sci., June 15, 2002; 115(12): 2475 - 2484. [Abstract] [Full Text] [PDF]
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 N. Q. Liu, A. S. Lossinsky, W. Popik, X. Li, C. Gujuluva, B. Kriederman, J. Roberts, T. Pushkarsky, M. Bukrinsky, M. Witte, et al. Human Immunodeficiency Virus Type 1 Enters Brain Microvascular Endothelia by Macropinocytosis Dependent on Lipid Rafts and the Mitogen-Activated Protein Kinase Signaling Pathway J. Virol., June 5, 2002; 76(13): 6689 - 6700. [Abstract] [Full Text] [PDF]
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R H Adamson, F E Curry, G Adamson, B Liu, Y Jiang, K Aktories, H Barth, A Daigeler, N Golenhofen, W Ness, et al. Rho and rho kinase modulation of barrier properties: cultured endothelial cells and intact microvessels of rats and mice J. Physiol., February 15, 2002; 539(1): 295 - 308. [Abstract] [Full Text] [PDF]
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 M. Vicente-Manzanares, J. R. Cabrero, M. Rey, M. Perez-Martinez, A. Ursa, K. Itoh, and F. Sanchez-Madrid A Role for the Rho-p160 Rho Coiled-Coil Kinase Axis in the Chemokine Stromal Cell-Derived Factor-1{alpha}-Induced Lymphocyte Actomyosin and Microtubular Organization and Chemotaxis J. Immunol., January 1, 2002; 168(1): 400 - 410. [Abstract] [Full Text] [PDF]
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G. P. van Nieuw Amerongen and V. W.M. van Hinsbergh Cytoskeletal Effects of Rho-Like Small Guanine Nucleotide-Binding Proteins in the Vascular System Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 300 - 311. [Abstract] [Full Text] [PDF]
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 G. P. v. N. Amerongen, M. A. Vermeer, P. Negre-Aminou, J. Lankelma, J. J. Emeis, and V. W. M. van Hinsbergh Simvastatin Improves Disturbed Endothelial Barrier Function Circulation, December 5, 2000; 102(23): 2803 - 2809. [Abstract] [Full Text] [PDF]
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J. S. Alexander Rho, Tyrosine Kinase, Ca2+, and Junctions in Endothelial Hyperpermeability Circ. Res., August 18, 2000; 87(4): 268 - 271. [Full Text] [PDF]
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D. Mehta, A. Rahman, and A. B. Malik Protein Kinase C-alpha Signals Rho-Guanine Nucleotide Dissociation Inhibitor Phosphorylation and Rho Activation and Regulates the Endothelial Cell Barrier Function J. Biol. Chem., June 15, 2001; 276(25): 22614 - 22620. [Abstract] [Full Text] [PDF]
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D. Thuringer, L. Maulon, and C. Frelin Rapid Transactivation of the Vascular Endothelial Growth Factor Receptor KDR/Flk-1 by the Bradykinin B2 Receptor Contributes to Endothelial Nitric-oxide Synthase Activation in Cardiac Capillary Endothelial Cells J. Biol. Chem., January 11, 2002; 277(3): 2028 - 2032. [Abstract] [Full Text] [PDF]
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K. E. Kamm and J. T. Stull Dedicated Myosin Light Chain Kinases with Diverse Cellular Functions J. Biol. Chem., February 9, 2001; 276(7): 4527 - 4530. [Full Text] [PDF]
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