The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor

Autores
González Pardo, María Verónica; D'elía, Noelia Laura; Berstuy, Annemieke; Boland, Ricardo Leopoldo; Russo, Ana Josefa
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have previously demonstrated that 1α,25 dihydroxy-vitamin D3 (1α,25(OH)2D3) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)2D3 exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)2D3, similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)2D3 treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D3 receptor (VDR). 1α,25(OH)2D3-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)2D3 on endothelial cells transformed by vGPCR.
Fil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Katholieke Universiteit Leuven; Bélgica
Fil: D'elía, Noelia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Berstuy, Annemieke. Katholieke Universiteit Leuven; Bélgica
Fil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Russo, Ana Josefa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Materia
Nfkb
1α,25(Oh)2-Vitamin D3
Endothelial Cells
Kaposi Sarcoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/62541
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/62541
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptorGonzález Pardo, María VerónicaD'elía, Noelia LauraBerstuy, AnnemiekeBoland, Ricardo LeopoldoRusso, Ana JosefaNfkb1α,25(Oh)2-Vitamin D3Endothelial CellsKaposi Sarcomahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We have previously demonstrated that 1α,25 dihydroxy-vitamin D3 (1α,25(OH)2D3) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)2D3 exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)2D3, similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)2D3 treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D3 receptor (VDR). 1α,25(OH)2D3-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)2D3 on endothelial cells transformed by vGPCR.Fil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Katholieke Universiteit Leuven; BélgicaFil: D'elía, Noelia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Berstuy, Annemieke. Katholieke Universiteit Leuven; BélgicaFil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Russo, Ana Josefa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaElsevier Science Inc2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/62541González Pardo, María Verónica; D'elía, Noelia Laura; Berstuy, Annemieke; Boland, Ricardo Leopoldo; Russo, Ana Josefa; The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor; Elsevier Science Inc; Steroids; 77; 5-2012; 1025-10320039-128XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0039128X12001808info:eu-repo/semantics/altIdentifier/doi/10.1016/j.steroids.2012.05.006info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:59Zoai:ri.conicet.gov.ar:11336/62541instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:06:59.806CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
title The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
spellingShingle The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
González Pardo, María Verónica
Nfkb
1α,25(Oh)2-Vitamin D3
Endothelial Cells
Kaposi Sarcoma
title_short The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
title_full The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
title_fullStr The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
title_full_unstemmed The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
title_sort The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor
dc.creator.none.fl_str_mv González Pardo, María Verónica
D'elía, Noelia Laura
Berstuy, Annemieke
Boland, Ricardo Leopoldo
Russo, Ana Josefa
author González Pardo, María Verónica
author_facet González Pardo, María Verónica
D'elía, Noelia Laura
Berstuy, Annemieke
Boland, Ricardo Leopoldo
Russo, Ana Josefa
author_role author
author2 D'elía, Noelia Laura
Berstuy, Annemieke
Boland, Ricardo Leopoldo
Russo, Ana Josefa
author2_role author
author
author
author
dc.subject.none.fl_str_mv Nfkb
1α,25(Oh)2-Vitamin D3
Endothelial Cells
Kaposi Sarcoma
topic Nfkb
1α,25(Oh)2-Vitamin D3
Endothelial Cells
Kaposi Sarcoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We have previously demonstrated that 1α,25 dihydroxy-vitamin D3 (1α,25(OH)2D3) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)2D3 exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)2D3, similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)2D3 treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D3 receptor (VDR). 1α,25(OH)2D3-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)2D3 on endothelial cells transformed by vGPCR.
Fil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Katholieke Universiteit Leuven; Bélgica
Fil: D'elía, Noelia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Berstuy, Annemieke. Katholieke Universiteit Leuven; Bélgica
Fil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Russo, Ana Josefa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
description We have previously demonstrated that 1α,25 dihydroxy-vitamin D3 (1α,25(OH)2D3) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)2D3 exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)2D3, similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)2D3 treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D3 receptor (VDR). 1α,25(OH)2D3-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)2D3 on endothelial cells transformed by vGPCR.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/62541
González Pardo, María Verónica; D'elía, Noelia Laura; Berstuy, Annemieke; Boland, Ricardo Leopoldo; Russo, Ana Josefa; The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor; Elsevier Science Inc; Steroids; 77; 5-2012; 1025-1032
0039-128X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/62541
identifier_str_mv González Pardo, María Verónica; D'elía, Noelia Laura; Berstuy, Annemieke; Boland, Ricardo Leopoldo; Russo, Ana Josefa; The NFkB pathway is down-regulated by 1α,25(OH)2-Vitamin D3 in endothelial cells transformed by Kaposi Sarcoma-associated herpes virus G protein coupled receptor; Elsevier Science Inc; Steroids; 77; 5-2012; 1025-1032
0039-128X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0039128X12001808
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.steroids.2012.05.006
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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