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Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability

Endothelial 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...

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Autores principales: Siddiqui, M. Rizwan, Komarova, Yulia A., Vogel, Stephen M., Gao, Xiaopei, Bonini, Marcelo G., Rajasingh, Johnson, Zhao, You-Yang, Brovkovych, Viktor, Malik, Asrar B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105546/
https://www.ncbi.nlm.nih.gov/pubmed/21624953
http://dx.doi.org/10.1083/jcb.201012129
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author Siddiqui, M. Rizwan
Komarova, Yulia A.
Vogel, Stephen M.
Gao, Xiaopei
Bonini, Marcelo G.
Rajasingh, Johnson
Zhao, You-Yang
Brovkovych, Viktor
Malik, Asrar B.
author_facet Siddiqui, M. Rizwan
Komarova, Yulia A.
Vogel, Stephen M.
Gao, Xiaopei
Bonini, Marcelo G.
Rajasingh, Johnson
Zhao, You-Yang
Brovkovych, Viktor
Malik, Asrar B.
author_sort Siddiqui, M. Rizwan
collection PubMed
description Endothelial 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.
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spelling pubmed-31055462011-11-30 Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability Siddiqui, M. Rizwan Komarova, Yulia A. Vogel, Stephen M. Gao, Xiaopei Bonini, Marcelo G. Rajasingh, Johnson Zhao, You-Yang Brovkovych, Viktor Malik, Asrar B. J Cell Biol Research Articles Endothelial 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. The Rockefeller University Press 2011-05-30 /pmc/articles/PMC3105546/ /pubmed/21624953 http://dx.doi.org/10.1083/jcb.201012129 Text en © 2011 Siddiqui et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Siddiqui, M. Rizwan
Komarova, Yulia A.
Vogel, Stephen M.
Gao, Xiaopei
Bonini, Marcelo G.
Rajasingh, Johnson
Zhao, You-Yang
Brovkovych, Viktor
Malik, Asrar B.
Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability
title Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability
title_full Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability
title_fullStr Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability
title_full_unstemmed Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability
title_short Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability
title_sort caveolin-1–enos signaling promotes p190rhogap-a nitration and endothelial permeability
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105546/
https://www.ncbi.nlm.nih.gov/pubmed/21624953
http://dx.doi.org/10.1083/jcb.201012129
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