title: S-nitrosylation regulates VE-cadherin phosphorylation and internalization in microvascular permeability.
abstract: The adherens junction complex, composed mainly of vascular endothelial (VE)-cadherin, β-catenin, p120, and γ-catenin, is the main element of the endothelial barrier in postcapillary venules.S-nitrosylation of β-catenin and p120 is an important step in proinflammatory agents-induced hyperpermeability. We investigated in vitro and in vivo whether or not VE-cadherin isS-nitrosylated using platelet-activating factor (PAF) as agonist. We report that PAF-stimulates S-nitrosylation of VE-cadherin, which disrupts its association with β-catenin. In addition, based on inhibition of nitric oxide production, our results strongly suggest that S-nitrosylation is required for VE-cadherin phosphorylation on tyrosine and for its internalization. Our results unveil an important mechanism to regulate phosphorylation of junctional proteins in association with S-nitrosylation.
authors.affiliation: Instituto de Inmunología, Universidad Austral de Chile, Valdivia, Chile;
authors.forename: Anita
authors.initials: A
authors.lastname: Guequén
authors.affiliation: Instituto de Inmunología, Universidad Austral de Chile, Valdivia, Chile;
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carrasco
authors.affiliation: Instituto de Inmunología, Universidad Austral de Chile, Valdivia, Chile;
authors.forename: Patricia
authors.initials: P
authors.lastname: Zamorano
authors.affiliation: Instituto de Inmunología, Universidad Austral de Chile, Valdivia, Chile;
authors.forename: Lorena
authors.initials: L
authors.lastname: Rebolledo
authors.affiliation: Instituto de Inmunología, Universidad Austral de Chile, Valdivia, Chile;
authors.forename: Pia
authors.initials: P
authors.lastname: Burboa
authors.affiliation: Instituto de Fisiología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile;
authors.forename: José
authors.initials: J
authors.lastname: Sarmiento
authors.affiliation: Departamento de Fisiología, P. Universidad Católica de Chile, Santiago, Chile; and.
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Boric
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey.
authors.forename: Adam
authors.initials: A
authors.lastname: Korayem
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey.
authors.forename: Walter N
authors.initials: WN
authors.lastname: Durán
authors.affiliation: Instituto de Inmunología, Universidad Austral de Chile, Valdivia, Chile; fabiolasanchez@uach.cl.
authors.forename: Fabiola A
authors.initials: FA
authors.lastname: Sánchez
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001692:Biological Transport; D015820:Cadherins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D051177:Catenins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D015538:Nitrosation; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D013997:Time Factors; D014443:Tyrosine; D014699:Venules / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D009569:Nitric Oxide; D010972:Platelet Activating Factor; D014443:Tyrosine; D051176:beta Catenin; D000095002:Delta Catenin; D000099152:Cadherin 5; C495270:CTNNB1 protein, human
keywords: S-nitrosylation; VE-cadherin; adherens junction; endothelial permeability; inflammation