| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224
Thrombin-induced endothelial cell barrier dysfunction is tightly linked to Ca2+-dependent cytoskeletal protein reorganization. In this study, we found that thrombin increased Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) activities in a Ca2+- and time-dependent manner in bovine pulmonary endothelium with maximal activity at 5 min. Pretreatment with KN-93, a specific CaM kinase II inhibitor, attenuated both thrombin-induced increases in monolayer permeability to albumin and decreases in transendothelial electrical resistance (TER). We next explored potential thrombin-induced CaM kinase II cytoskeletal targets and found that thrombin causes translocation and significant phosphorylation of nonmuscle filamin (ABP-280), which was attenuated by KN-93, whereas thrombin-induced myosin light chain phosphorylation was unaffected. Furthermore, a cell-permeable N-myristoylated synthetic filamin peptide (containing the COOH-terminal CaM kinase II phosphorylation site) attenuated both thrombin-induced filamin phosphorylation and decreases in TER. Together, these studies indicate that CaM kinase II activation and filamin phosphorylation may participate in thrombin-induced cytoskeletal reorganization and endothelial barrier dysfunction.
thrombin; filamin; myosin light chain phosphorylation; transendothelial electrical resistance
This article has been cited by other articles:
|
|
 |
|
  S. Sehrawat, X. Cullere, S. Patel, J. Italiano Jr., and T. N. Mayadas Role of Epac1, an Exchange Factor for Rap GTPases, in Endothelial Microtubule Dynamics and Barrier Function Mol. Biol. Cell, March 1, 2008; 19(3): 1261 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cai, D. Liu, and J. G.N. Garcia CaM Kinase II-dependent pathophysiological signalling in endothelial cells Cardiovasc Res, January 1, 2008; 77(1): 30 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Singh, K. L. McCann, and F. Imani MAPK and heat shock protein 27 activation are associated with respiratory syncytial virus induction of human bronchial epithelial monolayer disruption Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L436 - L445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Stahmann, A. Woods, D. Carling, and R. Heller Thrombin Activates AMP-Activated Protein Kinase in Endothelial Cells via a Pathway Involving Ca2+/Calmodulin-Dependent Protein Kinase Kinase {beta}. Mol. Cell. Biol., August 1, 2006; 26(16): 5933 - 5945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Herrmann, C. T. Morita, K. Lee, and D. J. Kusner Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells J. Leukoc. Biol., December 1, 2005; 78(6): 1397 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Goggel and S. Uhlig The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema Eur. Respir. J., May 1, 2005; 25(5): 849 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Clements, F. L. Minnear, H. A. Singer, R. S. Keller, and P. A. Vincent RhoA and Rho-kinase dependent and independent signals mediate TGF-{beta}-induced pulmonary endothelial cytoskeletal reorganization and permeability Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L294 - L306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Borbiev, A. Birukova, F. Liu, S. Nurmukhambetova, W. T. Gerthoffer, J. G. N. Garcia, and A. D. Verin p38 MAP kinase-dependent regulation of endothelial cell permeability Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L911 - L918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Glass and D. O. Bates The role of endothelial cell Ca2+ store release in the regulation of microvascular permeability in vivo Exp Physiol, July 1, 2004; 89(4): 343 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
P. V. Usatyuk, V. P. Fomin, S. Shi, J. G. N. Garcia, K. Schaphorst, and V. Natarajan Role of Ca2+ in diperoxovanadate-induced cytoskeletal remodeling and endothelial cell barrier function Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1006 - L1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Borbiev, A. D. Verin, A. Birukova, F. Liu, M. T. Crow, and J. G. N. Garcia Role of CaM kinase II and ERK activation in thrombin-induced endothelial cell barrier dysfunction Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L43 - L54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sato, Y. Morishima, and Y. Shirasaki 3-[2-[4-(3-Chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole Dihydrochloride 3.5 Hydrate (DY-9760e), a Novel Calmodulin Antagonist, Reduces Brain Edema through the Inhibition of Enhanced Blood-Brain Barrier Permeability after Transient Focal Ischemia J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1042 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. LIU, K. L. SCHAPHORST, A. D. VERIN, K. JACOBS, A. BIRUKOVA, R. M. DAY, N. BOGATCHEVA, D. P. BOTTARO, and J. G. N. GARCIA Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3{beta} FASEB J, July 1, 2002; 16(9): 950 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Dudek and J. G. N. Garcia Cytoskeletal regulation of pulmonary vascular permeability J Appl Physiol, October 1, 2001; 91(4): 1487 - 1500. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
