The proapoptotic protein Bim is up regulated by 1α,25-dihydroxyvitamin D3 and its receptor agonist in endothelial cells and transformed by viral GPCR associated to Kaposi sarcoma
We have previously shown that 1a,25-dihydroxyvitamin D3 [1a,25(OH)2D3] and its less calcemic analogTX 527 induce apoptosis via caspase-3 activation in endothelial cells (SVEC) and endothelial cells transformedby the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work,...
| Autores: | , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2015 |
| País: | Argentina |
| Recursos: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositório: | CONICET Digital (CONICET) |
| Idioma: | inglês |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/6334 |
| Acesso em linha: | http://hdl.handle.net/11336/6334 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Vitamin D Apoptosis Kaposi Sarcoma Endothelial Cells https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Resumo: | We have previously shown that 1a,25-dihydroxyvitamin D3 [1a,25(OH)2D3] and its less calcemic analogTX 527 induce apoptosis via caspase-3 activation in endothelial cells (SVEC) and endothelial cells transformedby the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, westudied whether intrinsic apoptotic pathway could be activated by changing the balance between antiand pro-apoptotic proteins. Time response qRT-PCR analysis demonstrated that the mRNA level ofanti-apoptotic gene Bcl-2 decreased after 12 h and increased after 48 h treatment with 1a,25(OH)2D3or TX 527 in SVEC and vGPCR cells, whereas its protein level remained unchanged through time.mRNA levels of pro-apoptotic gene Bax significantly increased only in SVEC after 24 and 48 h treatmentwith 1a,25(OH)2D3 and TX 527 although its protein levels remained unchanged in both cell lines. BimmRNA and protein levels increased in SVEC and vGPCR cells. Bim protein increase by 1a,25(OH)2D3and TX 527 was abolished when the expression of vitamin D receptor (VDR) was suppressed. On the otherhand, Bortezomib (0.25?1 nM), an inhibitor of NF-jB pathway highly activated in vGPCR cells, increasedBim protein levels and induced caspase-3 cleavage. Altogether, these results indicate that 1a,25(OH)2D3and TX 527 trigger apoptosis by Bim protein increase which turns into the activation of caspase-3 in SVECand vGPCR cells. Moreover, this effect is mediated by VDR and involves NF-jB pathway inhibition invGPCR. |
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