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

Authors
González Pardo, María Verónica; D'elía, Noelia Laura; Berstuy, Annemieke; Boland, Ricardo Leopoldo; Russo, Ana Josefa
Publication Year
2012
Language
English
Format
article
Status
Published version
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.
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
Subject
NFkB
1α,25(OH)2-Vitamin D3
Endothelial cells
Kaposi Sarcoma
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/62541