© 1997 American Heart Association, Inc.
Articles |
Oxidative Stress–Induced Actin Reorganization Mediated by the p38 Mitogen-Activated Protein Kinase/Heat Shock Protein 27 Pathway in Vascular Endothelial Cells
Centre de recherche en cancerologie de l'Universite Laval, L'Hotel-Dieu de Quebec (Canada).
Correspondence to Dr Jacques Huot, Le Centre de recherche en cancerologie de l'Universite Laval, L'Hotel-Dieu de Quebec, 11 Cote du Palais, Quebec, G1R-2J6, Canada. E-mail Jacques.Huot@phc.ulaval.ca
Vascular endothelial cells are constantly in contact with oxyradicals and must be especially well equipped to resist their toxic effects and generate appropriate physiological responses. Despite the importance of oxyradicals in the physiopathology of the vascular endothelium, the mechanisms regulating the oxidative response of endothelial cells are poorly understood. In the present study, we observed that H2O2 in concentrations that induced severe fragmentation of F-actin in fibroblasts rather induced a reorganization of F-actin in primary cultures of human umbilical vein endothelial cells (HUVECs) that was characterized by the accumulation of stress fibers, the recruitment of vinculin to focal adhesions, and the loss of membrane ruffles. H2O2 also induced in these cells a strong (10- to 14-fold) activation of the p38 mitogen-activated protein (MAP) kinase, which resulted in activation of MAP kinase–activated protein kinase-2/3 and phosphorylation of the F-actin polymerization modulator, heat shock protein 27 (HSP27). The MAP kinases extracellular-regulated kinase, and c-Jun N-terminal kinase/stress-activated protein kinase were only slightly increased by these treatments. Inhibiting p38 activity with the highly specific inhibitor SB203580 blocked the H2O2-induced endothelial microfilament responses. Moreover, fibroblasts acquired an endothelium-like SB203580-sensitive actin response when HSP27 concentration was increased by gene transfection to the same high level as found in HUVECs. The results indicate that activation of p38 MAP kinase in cells such as endothelial cells, which naturally express high level of HSP27, plays a central role in modulating microfilament responses to oxidative stress. Consequently, the p38 MAP kinase pathway may participate in the several oxyradical-activated functions of the endothelium that are associated with reorganization of microfilament network.
Key Words: oxidative stress • endothelial cell • p38 mitogen-activated protein kinase • heat shock protein 27 • F-actin
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Q. Wang and C. M. Doerschuk The p38 Mitogen-Activated Protein Kinase Mediates Cytoskeletal Remodeling in Pulmonary Microvascular Endothelial Cells Upon Intracellular Adhesion Molecule-1 Ligation J. Immunol., June 1, 2001; 166(11): 6877 - 6884. [Abstract] [Full Text] [PDF]
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R. G. Deschesnes, J. Huot, K. Valerie, and J. Landry Involvement of p38 in Apoptosis-associated Membrane Blebbing and Nuclear Condensation Mol. Biol. Cell, June 1, 2001; 12(6): 1569 - 1582. [Abstract] [Full Text] [PDF]
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J. M. Kyriakis and J. Avruch Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation Physiol Rev, April 1, 2001; 81(2): 807 - 869. [Abstract] [Full Text] [PDF]
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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]
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T. Takahashi, F. Hato, T. Yamane, H. Fukumasu, K. Suzuki, S. Ogita, Y. Nishizawa, and S. Kitagawa Activation of Human Neutrophil by Cytokine-Activated Endothelial Cells Circ. Res., March 2, 2001; 88(4): 422 - 429. [Abstract] [Full Text] [PDF]
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S. Sanada, M. Kitakaze, P. J. Papst, K. Hatanaka, H. Asanuma, T. Aki, Y. Shinozaki, H. Ogita, K. Node, S. Takashima, et al. Role of Phasic Dynamism of p38 Mitogen-Activated Protein Kinase Activation in Ischemic Preconditioning of the Canine Heart Circ. Res., February 2, 2001; 88(2): 175 - 180. [Abstract] [Full Text] [PDF]
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 D B. Sanders, D. F Larson, K. Hunter, M. Gorman, and B. Yang Comparison of tumor necrosis factor-effect on the expression of iNOS in macrophage and cardiac myocytes Perfusion, January 1, 2001; 16(1): 67 - 74. [Abstract] [PDF]
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N. Ohashi, A. Matsumori, Y. Furukawa, K. Ono, M. Okada, A. Iwasaki, T. Miyamoto, A. Nakano, and S. Sasayama Role of p38 Mitogen-Activated Protein Kinase in Neointimal Hyperplasia After Vascular Injury Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2521 - 2526. [Abstract] [Full Text] [PDF]
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 S. J. Charette, J. N. Lavoie, H. Lambert, and J. Landry Inhibition of Daxx-Mediated Apoptosis by Heat Shock Protein 27 Mol. Cell. Biol., October 15, 2000; 20(20): 7602 - 7612. [Abstract] [Full Text]
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J. P. Leger, F. M. Smith, and R. W. Currie Confocal Microscopic Localization of Constitutive and Heat Shock-Induced Proteins HSP70 and HSP27 in the Rat Heart Circulation, October 3, 2000; 102(14): 1703 - 1709. [Abstract] [Full Text] [PDF]
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K. K. Griendling, D. Sorescu, B. Lassegue, and M. Ushio-Fukai Modulation of Protein Kinase Activity and Gene Expression by Reactive Oxygen Species and Their Role in Vascular Physiology and Pathophysiology Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2175 - 2183. [Abstract] [Full Text] [PDF]
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S. Meloche, J. Landry, J. Huot, F. Houle, F. Marceau, and E. Giasson p38 MAP kinase pathway regulates angiotensin II-induced contraction of rat vascular smooth muscle Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H741 - H751. [Abstract] [Full Text] [PDF]
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F.-X. Beck, W. Neuhofer, and E. Muller Molecular chaperones in the kidney: distribution, putative roles, and regulation Am J Physiol Renal Physiol, August 1, 2000; 279(2): F203 - F215. [Abstract] [Full Text] [PDF]
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C. G. Kevil, T. Oshima, B. Alexander, L. L. Coe, and J. S. Alexander H2O2-mediated permeability: role of MAPK and occludin Am J Physiol Cell Physiol, July 1, 2000; 279(1): C21 - C30. [Abstract] [Full Text] [PDF]
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D. Talmor, A. Applebaum, A. Rudich, Y. Shapira, and A. Tirosh Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass Circ. Res., May 12, 2000; 86(9): 1004 - 1007. [Abstract] [Full Text] [PDF]
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R. Kacimi, J. Chentoufi, N. Honbo, C. S. Long, and J. S. Karliner Hypoxia differentially regulates stress proteins in cultured cardiomyocytes: Role of the p38 stress-activated kinase signaling cascade, and relation to cytoprotection Cardiovasc Res, April 1, 2000; 46(1): 139 - 150. [Abstract] [Full Text] [PDF]
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S. Rousseau, F. Houle, H. Kotanides, L. Witte, J. Waltenberger, J. Landry, and J. Huot Vascular Endothelial Growth Factor (VEGF)-driven Actin-based Motility Is Mediated by VEGFR2 and Requires Concerted Activation of Stress-activated Protein Kinase 2 (SAPK2/p38) and Geldanamycin-sensitive Phosphorylation of Focal Adhesion Kinase J. Biol. Chem., March 31, 2000; 275(14): 10661 - 10672. [Abstract] [Full Text] [PDF]
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J.-i. Abe, C. P. Baines, and B. C. Berk Role of Mitogen-Activated Protein Kinases in Ischemia and Reperfusion Injury : The Good and the Bad Circ. Res., March 31, 2000; 86(6): 607 - 609. [Full Text] [PDF]
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K. Kujime, S. Hashimoto, Y. Gon, K. Shimizu, and T. Horie p38 Mitogen-Activated Protein Kinase and c-Jun-NH2-Terminal Kinase Regulate RANTES Production by Influenza Virus-Infected Human Bronchial Epithelial Cells J. Immunol., March 15, 2000; 164(6): 3222 - 3228. [Abstract] [Full Text] [PDF]
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K. Breitschopf, J. Haendeler, P. Malchow, A. M. Zeiher, and S. Dimmeler Posttranslational Modification of Bcl-2 Facilitates Its Proteasome-Dependent Degradation: Molecular Characterization of the Involved Signaling Pathway Mol. Cell. Biol., March 1, 2000; 20(5): 1886 - 1896. [Abstract] [Full Text]
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C. Schafer, P. Clapp, M. J. Welsh, R. Benndorf, and J. A. Williams HSP27 expression regulates CCK-induced changes of the actin cytoskeleton in CHO-CCK-A cells Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1032 - C1043. [Abstract] [Full Text] [PDF]
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J. H. Park, N. Okayama, D. Gute, A. Krsmanovic, H. Battarbee, and J. S. Alexander Hypoxia/aglycemia increases endothelial permeability: role of second messengers and cytoskeleton Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1066 - C1074. [Abstract] [Full Text] [PDF]
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M. Wagner, I. Hermanns, F. Bittinger, and C. J. Kirkpatrick Induction of stress proteins in human endothelial cells by heavy metal ions and heat shock Am J Physiol Lung Cell Mol Physiol, November 1, 1999; 277(5): L1026 - L1033. [Abstract] [Full Text] [PDF]
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H. Massaeli, C. Hurtado, J. A. Austria, and G. N. Pierce Oxidized low-density lipoprotein induces cytoskeletal disorganization in smooth muscle cells Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H2017 - H2025. [Abstract] [Full Text] [PDF]
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C. Kunsch and R. M. Medford Oxidative Stress as a Regulator of Gene Expression in the Vasculature Circ. Res., October 15, 1999; 85(8): 753 - 766. [Abstract] [Full Text] [PDF]
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M. Rolli, A. Kotlyarov, K. M. Sakamoto, M. Gaestel, and A. Neininger Stress-induced Stimulation of Early Growth Response Gene-1 by p38/Stress-activated Protein Kinase 2 Is Mediated by a cAMP-responsive Promoter Element in a MAPKAP Kinase 2-independent Manner J. Biol. Chem., July 9, 1999; 274(28): 19559 - 19564. [Abstract] [Full Text] [PDF]
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R. M. A. van Gorp, J. L. V. Broers, C. P. M. Reutelingsperger, N. M. H. J. Bronnenberg, G. Hornstra, M. C. E. van Dam-Mieras, and J. W. M. Heemskerk Peroxide-induced membrane blebbing in endothelial cells associated with glutathione oxidation but not apoptosis Am J Physiol Cell Physiol, July 1, 1999; 277(1): C20 - C28. [Abstract] [Full Text] [PDF]
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S. Vepa, W. M. Scribner, N. L. Parinandi, D. English, J. G. N. Garcia, and V. Natarajan Hydrogen peroxide stimulates tyrosine phosphorylation of focal adhesion kinase in vascular endothelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L150 - L158. [Abstract] [Full Text] [PDF]
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 G. Xi, R. F. Keep, Y. Hua, J. Xiang, J. T. Hoff, and R. L. Macdonald Attenuation of Thrombin-Induced Brain Edema by Cerebral Thrombin Preconditioning • Editorial Comment Stroke, June 1, 1999; 30(6): 1247 - 1255. [Abstract] [Full Text] [PDF]
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T. Matsumoto, K. Yokote, K. Tamura, M. Takemoto, H. Ueno, Y. Saito, and S. Mori Platelet-derived Growth Factor Activates p38 Mitogen-activated Protein Kinase through a Ras-dependent Pathway That Is Important for Actin Reorganization and Cell Migration J. Biol. Chem., May 14, 1999; 274(20): 13954 - 13960. [Abstract] [Full Text] [PDF]
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