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dc.contributor.authorSiddiqui, M. Rizwan
dc.contributor.authorKomarova, Yulia A.
dc.contributor.authorVogel, Stephen M.
dc.contributor.authorGao, Xiaopei
dc.contributor.authorBonini, Marcelo G.
dc.contributor.authorRajasingh, Johnson
dc.contributor.authorZhao, You-Yang
dc.contributor.authorBrovkovych, Viktor
dc.contributor.authorMalik, Asrar B.
dc.date.accessioned2012-03-09T19:44:42Z
dc.date.available2012-03-09T19:44:42Z
dc.date.issued2011-05-30
dc.identifier.bibliographicCitationSiddiqui, M. R., Komarova, Y. A., Vogel, S. M., Gao, X., Bonini, M. G., Rajasingh, J., Zhao, Y. Y., Brovkovych, V., & Malik, A. B. 2011. Caveolin-1-eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability. Journal of Cell Biology, 193(5): 841-850. DOI: 10.1083/jcb.201012129en
dc.identifier.issn0021-9525
dc.identifier.otherDOI: 10.1083/jcb.201012129
dc.identifier.urihttp://hdl.handle.net/10027/8183
dc.description© 2011 Siddiqui et al. The original version is available through Rockefeller University Press at DOI: 10.1083/jcb.201012129.en
dc.description.abstractEndothelial barrier function is regulated by adherens junctions (AJs) and caveolae-mediated transcellular pathways. The opening of AJs that is observed in caveolin-1-/- (Cav-1-/-) endothelium suggests that Cav-1 is necessary for AJ assembly or maintenance. Here, using endothelial cells isolated from Cav-1-/-mice, we show that Cav-1 deficiency induced the activation of endothelial nitric oxide synthase (eNOS) and the generation of nitric oxide (NO) and peroxynitrite. We assessed S-nitrosylation and nitration of AJ-associated proteins to identify downstream NO redox signaling targets. We found that the GTPase-activating protein (GAP) p190RhoGAP-A was selectively nitrated at Tyr1105, resulting in impaired GAP activity and RhoA activation. Inhibition of eNOS or RhoA restored AJ integrity and diminished endothelial hyperpermeability in Cav-1-/-mice. Thrombin, a mediator of increased endothelial permeability, also induced nitration of p120-catenin–associated p190RhoGAP-A. Thus, eNOS-dependent nitration of p190RhoGAP-A represents a crucial mechanism for AJ disassembly and resultant increased endothelial permeability.en
dc.description.sponsorshipThis work was supported by National Institutes of Health grants R01 HL 45638 and P01 HL 60678 to A.B. Malik and R01 HL103922 to Y. Komarova.en
dc.language.isoen_USen
dc.publisherRockefeller University Pressen
dc.subjectnitric oxide synthaseen
dc.subjectadherens junctionen
dc.subjectendothelial permeabilityen
dc.titleCaveolin-1–eNOS Signaling Promotes p190RhoGAP-A Nitration and Endothelial Permeabilityen
dc.typeArticleen


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