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dc.creatorGonzález Pardo, María Verónica-
dc.creatorVerstuyf, A.-
dc.creatorBoland, Ricardo Leopoldo-
dc.creatorRusso, Ana Josefa-
dc.date2017-07-28T21:38:10Z-
dc.date2017-07-28T21:38:10Z-
dc.date2013-08-
dc.date2017-07-28T17:53:25Z-
dc.date.accessioned2019-04-29T15:54:47Z-
dc.date.available2019-04-29T15:54:47Z-
dc.identifierGonzález Pardo, María Verónica; Verstuyf, A.; Boland, Ricardo Leopoldo; Russo, Ana Josefa; Vitamin D analogue TX 527 down-regulates the NF-κB pathway and controls the proliferation of endothelial cells transformed by Kaposi sarcoma herpesvirus; Wiley; British Journal of Pharmacology; 169; 7; 8-2013; 1635-1645-
dc.identifier0007-1188-
dc.identifierhttp://hdl.handle.net/11336/21613-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/305195-
dc.descriptionBACKGROUND AND PURPOSE: The Kaposi sarcoma (KS)-associated herpesvirus GPCR (vGPCR) is a key molecule in the pathogenesis of KS, where it increases NF-κB gene expression and activates the NF-κB pathway. We investigated whether the less calcemic vitamin D analogue TX 527 inhibited the proliferation of endothelial cells transformed by vGPCR by modulation of the NF-κB pathway. EXPERIMENTAL APPROACH: Endothelial cells transformed by vGPCR (SVEC-vGPCR) were treated with TX 527. Proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and cell cycle by flow cytometry. mRNA and protein levels were measured by real-time quantitative reverse transcriptase-PCR (qRT-PCR) and immunoblot analysis respectively. KEY RESULTS: TX 527, similar to bortezomib (0.5 nM), a proteasome inhibitor that inhibits the activation of NF-κB, reduced proliferation and induced G0/G1 cell cycle arrest in SVEC-vGPCR. TX 527 like 1α,25(OH)2D3, biological active form of vitamin D, decreased the activity of NF-κB comparable with the effect of bortezomib. Time-response studies showed that TX 527 significantly decreased NF-κB and increased IκBα mRNA and protein levels. The increase of IκBα was accompanied by a reduction in p65/NF-κB translocation to the nucleus. These responses were abolished when vitamin D receptor (VDR) expression was suppressed by stable transfection of shRNA against VDR. In parallel with NF-κB inhibition, there was a down-regulation of inflammatory genes such as IL-6, CCL2/MCP and CCL20/MIP3α. CONCLUSIONS AND IMPLICATIONS: These results suggest that the anti-proliferative effects of the vitamin D analogue TX 527 in SVEC-vGPCR occur by modulation of the NF-κB pathway and are VDR dependent.-
dc.descriptionFil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Verstuyf, A.. Katholikie Universiteit Leuven; Bélgica-
dc.descriptionFil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Russo, Ana Josefa. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherWiley-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/bph.12219-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/bph.12219/abstract-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectTX 527-
dc.subjectNFKB-
dc.subjectKAPOSI SARCOMA-
dc.subjectVITAMIN D ANALOGS-
dc.subjectBioquímica y Biología Molecular-
dc.subjectCiencias Biológicas-
dc.subjectCIENCIAS NATURALES Y EXACTAS-
dc.titleVitamin D analogue TX 527 down-regulates the NF-κB pathway and controls the proliferation of endothelial cells transformed by Kaposi sarcoma herpesvirus-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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