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In human umbilical vein endothelial cells (HUVECs) the PTP inhibitors phenylarsine oxide (PAO) and pervanadate induced proteolysis of the tight junction protein occludin. Occludin proteolysis was inhibited by the metalloproteinase inhibitor 1,10-phenanthroline (PHEN), but not by inhibitors against other types of proteases. The junctional proteins ZO-1, cadherin and \u03b2-catenin were not cleaved. Under conditions of occludin proteolysis, PAO treatment elevated permeability for FITC-dextran. Simultaneous incubation of HUVECs with PAO and PHEN inhibited the rise in permeability by more than 60%. PAO treatment lead to progressive disappearance of occludin from the cell periphery. In contrast, ZO-1, cadherin and \u03b2-catenin retained their positions at the sites of intercellular contact. Simultaneous administration of PAO and PHEN greatly prevented the redistribution of occludin. These results demonstrate a selective cleavage of occludin by a metalloproteinase and suggest that this process can contribute to the control of paracellular permeability in endothelial cells.<\/jats:p>","DOI":"10.1242\/jcs.112.23.4347","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:29:48Z","timestamp":1619371788000},"page":"4347-4356","source":"Crossref","is-referenced-by-count":141,"title":["Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition"],"prefix":"10.1242","volume":"112","author":[{"given":"Marco","family":"Wachtel","sequence":"first","affiliation":[{"name":"1 Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Zentrum, CH-8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Frei","sequence":"additional","affiliation":[{"name":"University Hospital Zurich 2 Department of Neurosurgery , , CH-8001 Zurich, Switzerl"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Ehler","sequence":"additional","affiliation":[{"name":"3 Institute of Cell Biology, Swiss Federal Institute of Technology, ETH H\u00f6nggerberg, CH-8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Fontana","sequence":"additional","affiliation":[{"name":"University Hospital Zurich 4 Section of Clinical Immunology, Department of Internal Medicine , , CH-8001 Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaspar","family":"Winterhalter","sequence":"additional","affiliation":[{"name":"1 Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Zentrum, CH-8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio M.","family":"Gloor","sequence":"additional","affiliation":[{"name":"1 Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Zentrum, CH-8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,12,1]]},"reference":[{"key":"2024071016365686300_JOCES_112_23_4347C1","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1006\/dbio.1996.0336","article-title":"Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure-remodeling of the neuroepithelium prior to neurogenesis","volume":"180","author":"Aaku-Sarraste","year":"1996","journal-title":"Dev. 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