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Thrombin induced permeability changes in all EC, and induced significantly elevated rates of monolayer permeability in PKC\u03b1EC. Conversely, the basal level of permeability was significantly blunted in PKC\u03b4EC, resulting in diminished thrombin-induced changes in permeability. PKC inhibitors, G\u00f66976 and rottlerin, reversed the effects of PKC\u03b1 and PKC\u03b4 overexpression on permeability, respectively. Immunoblot analyses demonstrated significantly less \u03b2-catenin associated with the cytoskeletal subcellular fraction in thrombin-treated PKC\u03b1EC, an effect blocked by pretreatment with G\u00f66976. PKC\u03b4EC contained significantly greater numbers of focal contacts per cell. Thrombin enhanced RhoA GTPase activity in all EC; with a 3-fold greater level of activity in PKC\u03b4EC. Rottlerin significantly blunted RhoA GTPase activity in all EC. Overexpression of RhoA dominant-negative cDNA diminished the size and number of focal contacts in EC, and significantly enhanced the basal rate of PKC\u03b4EC monolayer permeability. These findings demonstrate that monolayer permeability changes are differentially regulated by PKC isoenzymes, suggesting that PKC\u03b1 promotes endothelial barrier dysfunction and PKC\u03b4 enhances basal endothelial barrier function.<\/jats:p>","DOI":"10.1165\/rcmb.2002-0085oc","type":"journal-article","created":{"date-parts":[[2003,4,21]],"date-time":"2003-04-21T14:34:15Z","timestamp":1050935655000},"page":"626-636","source":"Crossref","is-referenced-by-count":47,"title":["Role of Protein Kinase C Isoforms in Rat Epididymal Microvascular Endothelial Barrier Function"],"prefix":"10.1093","volume":"28","author":[{"given":"Elizabeth O.","family":"Harrington","sequence":"first","affiliation":[{"name":"Pulmonary Vascular Biology Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi L.","family":"Brunelle","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Biology Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Shannon","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Biology Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Biology Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin","family":"Mennella","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Biology Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Rounds","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Biology Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,5,1]]},"reference":[{"key":"2026030623541250300_BIB1","first-page":"117","volume":"43","year":"1995","journal-title":"J. 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