Association between adherens junctions and tight junctions via Rap1 promotes barrier protective effects of oxidized phospholipids.
Other Scholarly Work
Birukova, Anna A, Zebda, Noureddine, Fu, Panfeng et al. (2011). Association between adherens junctions and tight junctions via Rap1 promotes barrier protective effects of oxidized phospholipids.
. JOURNAL OF CELLULAR PHYSIOLOGY, 226(8), 2052-2062. 10.1002/jcp.22543
Birukova, Anna A, Zebda, Noureddine, Fu, Panfeng et al. (2011). Association between adherens junctions and tight junctions via Rap1 promotes barrier protective effects of oxidized phospholipids.
. JOURNAL OF CELLULAR PHYSIOLOGY, 226(8), 2052-2062. 10.1002/jcp.22543
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.
