iNOS activation regulates b-catenin association with its partners in endothelial cells

Gonzalez, Deyanira; Rojas, Armando; Herrera, Maria Beatriz; Conlan, R. Steven

Mostrar el registro sencillo de la publicación

dc.contributor.author	Gonzalez, Deyanira
dc.contributor.author	Rojas, Armando
dc.contributor.author	Herrera, Maria Beatriz
dc.contributor.author	Conlan, R. Steven
dc.date.accessioned	2017-11-22T21:00:52Z
dc.date.available	2017-11-22T21:00:52Z
dc.date.issued	2012
dc.identifier.uri	http://repositorio.ucm.cl/handle/ucm/1331
dc.description.abstract	Background: Signals that disrupt b-catenin association to cadherins may influence the translocation of b-catenin to the nucleus to regulate transcription. Post-translational modification of proteins is a signalling event that may lead to changes in structural conformation, association or function of the target proteins. NO and its derivatives induce nitration of proteins during inflammation. It has been described that animals treated with NO donors showed increased permeability due to modulation of VE-cadherin/catenin complex. We, therefore, aim to evaluate the effect of iNOS activation on the expression, nuclear localisation and function of b-catenin in endothelial cells. Methodology/Principal Findings: Expression, nuclear localisation, post-translational modifications and function of bcatenin was analysed by cell fractionation, immunoprecipitation, immunoblots, QRT-PCR and permeability assays in murine endothelial cells (H5V). Influence of macrophage activation on expression of VE-cadherin/p120-catenin/b-catenin complex in co-cultured H5V cells was also assessed. Activation of macrophages to produce NO provoked a decrease in VE-cadherin/ p120-catenin/b-catenin expression in H5V cells. Phosphorylation of b-catenin, p120-catenin and VE-cadherin, and reduction in the barrier properties of the cell monolayer was associated with iNOS induction. Moreover, high NO levels provoked nitration of b-catenin, and induced its translocation to the nucleus. In the nucleus of NOS activated cells, nitration levels of b-catenin influenced its association with TCF4 and p65 proteins. High levels of NO altered b-catenin mediated gene expression of NFkB and Wnt target genes without affecting cell viability. Conclusions: NOS activity modulates b-catenin post-translational modifications, function and its association with different partners to promote endothelial cell survival. Therapeutic manipulation of iNOS levels may remove a critical cytoprotective mechanism of importance in tumour angiogenesis.	es_CL
dc.language.iso	en	es_CL
dc.rights	Atribución-NoComercial-SinDerivadas 3.0 Chile	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/cl/	*
dc.source	PLoS ONE, 7(12), e52964	es_CL
dc.title	iNOS activation regulates b-catenin association with its partners in endothelial cells	es_CL
dc.type	Article	es_CL
dc.ucm.facultad	Facultad de Medicina	es_CL
dc.ucm.indexacion	Scopus	es_CL
dc.ucm.indexacion	Isi	es_CL
dc.ucm.doi	doi.org/10.1371/journal.pone.0052964	es_CL