Association between adherens junctions and tight junctions via Rap1 promotes barrier protective effects of oxidized phospholipids.

Abstract

Previous studies showed that cyclopenthenone-containing products resulting from oxidation of a natural phospholipid, 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) exhibit potent barrier-protective effects in the in vitro and in vivo models of lung endothelial cell (EC) barrier dysfunction, and these effects are associated with enhancement of peripheral actin cytoskeleton, cell-cell and cell-substrate contacts driven by activation of Rac and Cdc42 GTPases. Rap1 GTPase is another member of small GTPase family involved in control of cell-cell interactions; however, its involvement in EC barrier-protective effects by OxPAPC remains unknown. This study examined a role of Rap1 in regulation of OxPAPC-induced interactions in adherens junctions (AJ) and tight junctions (TJ) as a novel mechanism of EC barrier preservation in vitro and in vivo. Immunofluorescence analysis, subcellular fractionation, and co-immunoprecipitation assays indicate that OxPAPC promoted accumulation of AJ proteins: VE-cadherin, p120-catenin, and β-catenin; and TJ proteins: ZO-1, occludin, and JAM-A in the cell membrane, and induced novel cross-interactions between AJ and TJ protein complexes, that were dependent on OxPAPC-induced Rap1 activation. Inhibition of Rap1 function suppressed OxPAPC-mediated pulmonary EC barrier enhancement and AJ and TJ interactions in vitro, as well as inhibited protective effects of OxPAPC against ventilator-induced lung injury in vivo. These results show for the first time a role of Rap1-mediated association between adherens junctions and tight junction complexes in the OxPAPC-induced pulmonary vascular EC barrier protection.

• Authors: Anna A Birukova, Noureddine Zebda, Panfeng Fu, Valery Poroyko, Ivan Cokic, Konstantin G Birukov
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 226 Issue 8 Pg. 2052-62 (Aug 2011) ISSN: 1097-4652 [Electronic] United States
• PMID: 21520057 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Wiley-Liss, Inc.

Chemical References

• Antigens, CD
• Cadherins
• Catenins
• Cell Adhesion Molecules
• F11R protein, human
• Immunoglobulins
• Membrane Proteins
• OCLN protein, human
• Occludin
• Ocln protein, mouse
• Phosphatidylcholines
• Phosphoproteins
• Receptors, Cell Surface
• Shelterin Complex
• TERF2IP protein, human
• TJP1 protein, human
• Telomere-Binding Proteins
• Tjp1 protein, mouse
• Zonula Occludens-1 Protein
• beta Catenin
• cadherin 5
• oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
• Delta Catenin

Topics

• Adherens Junctions (metabolism)
• Animals
• Antigens, CD (metabolism)
• Cadherins (metabolism)
• Catenins (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cell Line
• Endothelial Cells (metabolism)
• Humans
• Immunoglobulins (metabolism)
• Lung (metabolism)
• Male
• Membrane Proteins (metabolism)
• Mice
• Occludin
• Phosphatidylcholines (metabolism)
• Phosphoproteins (metabolism)
• Pulmonary Artery (metabolism)
• Receptors, Cell Surface
• Shelterin Complex
• Telomere-Binding Proteins (metabolism)
• Tight Junctions (metabolism)
• Ventilator-Induced Lung Injury (metabolism)
• Zonula Occludens-1 Protein
• beta Catenin (metabolism)
• Delta Catenin