Phospholipase D2 regulates endothelial permeability through cytoskeleton reorganization and occludin downregulation
| Autor: | Zeiller, Caroline, Mebarek, Saïda, Jaafar, Rami, Pirola, Luciano, Lagarde, Michel, Prigent, Annie-France, Némoz, Georges |
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| Přispěvatelé: | Vericel, Evelyne, Cardiovasculaire, obésité et diabète - Rôles spécifiques des sous-fractions des LDL oxydées et des HDL dans les mécanismes physiopathologiques de l'athérosclérose. acronyme: LiSA, Lipoprotein Subspecies in Atherosclerosis. - - LISA2005 - ANR-05-PCOD-0019 - COD - VALID, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-05-PCOD-0019,LISA,Rôles spécifiques des sous-fractions des LDL oxydées et des HDL dans les mécanismes physiopathologiques de l'athérosclérose. acronyme: LiSA, Lipoprotein Subspecies in Atherosclerosis.(2005) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Signal Transduction
MESH: Membrane Microdomains MESH: Umbilical Veins MESH: Actins MESH: Down-Regulation Raf-1 kinase MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: RNA Small Interfering MESH: Cytoskeleton MESH: Blotting Western MESH: Fluorescent Antibody Technique stress fibres MESH: RNA Messenger lipid rafts MESH: Humans MESH: Phosphatidic Acids phosphatidic acid [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition MAP kinases MESH: Phospholipase D MESH: Proto-Oncogene Proteins c-raf MESH: Endothelium Vascular MESH: Membrane Proteins MESH: Mitogen-Activated Protein Kinase 3 [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition MESH: Cells Cultured MESH: Mitogen-Activated Protein Kinase 1 |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Cell Research Biochimica et Biophysica Acta-Molecular Cell Research, 2009, 1793 (7), pp.1236-49. ⟨10.1016/j.bbamcr.2009.04.001⟩ |
| ISSN: | 0167-4889 |
| Popis: | International audience; Endothelial permeability is controlled by adhesive strengths which connect cells to each other through interendothelial junctions and by contractile forces associated with cytoskeleton reorganization. Phospholipase D (PLD) activation resulting in the generation of phosphatidic acid (PA) is increasingly recognized as a key event in the initiation of various cell responses. In human umbilical vein endothelial cells (HUV-EC), enhancement of intracellular PA by a variety of approaches increased the permeability of endothelial cell monolayers and induced stress fibre formation. Using adenovirus-mediated overexpression and siRNA silencing, we showed that PLD2 but not PLD1 was involved in the enhancement of basal permeability through cytoskeleton reorganization. Furthermore, PLD2 overexpression induced ERK1/2 activation and downregulated the expression of occludin, a major component of tight junctions. A substantial part of PLD2 protein was associated with the low-density caveolin-rich fractions isolated on sucrose gradients. The Raf-1 specific inhibitor GW-5074 drastically reduced hyperpermeability induced by PLD2 overexpression, and inhibited PA-mediated increase of endothelial permeability and ERK1/2 activation. On the whole, the present results demonstrate the selective role of PLD2 isoform in the control of endothelial permeability through a mechanism involving both stress fibre formation and contraction, and occludin downregulation, possibly resulting from PA-mediated activation of Raf-1. |
| Databáze: | OpenAIRE |
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