S-Nitrosation of β-Catenin and p120 Catenin A Novel Regulatory Mechanism in Endothelial Hyperpermeability

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dc.contributor.authorMarin, Natalie
dc.contributor.authorZamorano, Patricia
dc.contributor.authorCarrasco, Rodrigo
dc.contributor.authorMujica, Patricio
dc.contributor.authorGonzalez, Francisco G.
dc.contributor.authorQuezada, Claudia
dc.contributor.authorMeininger, Cynthia J.
dc.contributor.authorBoric, Mauricio P.
dc.contributor.authorDuran, Walter N.
dc.contributor.authorSanchez, Fabiola A.
dc.date.accessioned2025-01-20T23:57:05Z
dc.date.available2025-01-20T23:57:05Z
dc.date.issued2012
dc.description.abstractRationale: Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of endothelial nitric oxide synthase (eNOS) to cytosol and stimulation of eNOS-derived nitric oxide signaling cascade. The mechanisms by which nitric oxide signaling regulates permeability at adherens junctions are still incompletely understood.
dc.description.abstractObjective: We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins.
dc.description.abstractMethods and Results: We measured PAF-stimulated SNO of beta-catenin and p120-catenin (p120) in 3 cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein), and postcapillary venular endothelial cells (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of beta-catenin and p120 at the adherens junction and with hyperpermeability. Tumor necrosis factor-alpha increased nitric oxide production and caused similar increase in SNO as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced SNO of beta-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of nitric oxide production and of SNO blocked PAF-induced SNO and hyperpermeability, whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with vascular endothelial-cadherin.
dc.description.abstractConclusions: Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability. (Circ Res. 2012;111:553-563.)
dc.fuente.origenWOS
dc.identifier.doi10.1161/CIRCRESAHA.112.274548
dc.identifier.eissn1524-4571
dc.identifier.issn0009-7330
dc.identifier.urihttps://doi.org/10.1161/CIRCRESAHA.112.274548
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95189
dc.identifier.wosidWOS:000307945600011
dc.issue.numero5
dc.language.isoen
dc.pagina.finalU248
dc.pagina.inicio553
dc.revistaCirculation research
dc.rightsacceso restringido
dc.subjectS-nitrosation
dc.subjectadherens junction
dc.subjectmicrovascular permeability
dc.subjectnitric oxide
dc.subjectp120
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleS-Nitrosation of β-Catenin and p120 Catenin A Novel Regulatory Mechanism in Endothelial Hyperpermeability
dc.typeartículo
dc.volumen111
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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