The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner

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dc.contributor.authorStrauss, Randy E.en
dc.contributor.authorMezache, Louisaen
dc.contributor.authorVeeraraghavan, Rengasayeeen
dc.contributor.authorGourdie, Robert G.en
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentSchool of Medicineen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2021-08-26T18:45:27Zen
dc.date.available2021-08-26T18:45:27Zen
dc.date.issued2021-08-12en
dc.date.updated2021-08-26T13:27:14Zen
dc.description.abstractThe Cx43 carboxyl-terminus (CT) mimetic peptide, αCT1, originally designed to bind to Zonula Occludens 1 (ZO1) and thereby inhibit Cx43/ZO1 interaction, was used as a tool to probe the role of Cx43/ZO1 association in regulation of epithelial/endothelial barrier function. Using both in vitro and ex vivo methods of barrier function measurement, including Electric Cell-Substrate Impedance Sensing (ECIS), a TRITC-dextran Transwell permeability assay, and a FITC-dextran cardiovascular leakage protocol involving Langendorff-perfused mouse hearts, αCT1 was found to protect the endothelium from thrombin-induced breakdown in cell–cell contacts. Barrier protection was accompanied by significant remodeling of the F-actin cytoskeleton, characterized by a redistribution of F-actin away from the cytoplasmic and nuclear regions of the cell, towards the endothelial cell periphery, in association with alterations in cellular chiral orientation distribution. In line with observations of increased cortical F-actin, αCT1 upregulated cell–cell border localization of endothelial VE-cadherin, the tight junction protein Zonula Occludens 1 (ZO1), and the Gap Junction Protein (GJ) Connexin43 (Cx43). A ZO1 binding-incompetent variant of αCT1, αCT1-I, indicated that these effects on barrier function and barrier-associated proteins, were likely associated with Cx43 CT sequences retaining ability to interact with ZO1. These results implicate the Cx43 CT and its interaction with ZO1, in the regulation of endothelial barrier function, while revealing the therapeutic potential of αCT1 in the treatment of vascular edema.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationStrauss, R.E.; Mezache, L.; Veeraraghavan, R.; Gourdie, R.G. The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner. Biomolecules 2021, 11, 1192.en
dc.identifier.doihttps://doi.org/10.3390/biom11081192en
dc.identifier.urihttp://hdl.handle.net/10919/104725en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCx43en
dc.subjectZonula Occludens 1en
dc.subjectbarrier functionen
dc.subjecttight junctionsen
dc.subjectadherens junctionsen
dc.subjectactin cytoskeletonen
dc.subjectendothelial cellsen
dc.titleThe Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manneren
dc.title.serialBiomoleculesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)
Scholarly Works, Biomedical Engineering and Mechanics
Scholarly Works, Fralin Biomedical Research Institute at VTC
Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)