Expression of pro and anti apoptotic proteins regulated by vitamin D agonist in endotelial cells

VERONICA GONZALEZ PARDO; ANNEMIEKE VERSTUYF; RICARDO BOLAND; ANA RUSSO DE BOLAND

Buenos Aires

Congreso; SAIB: Molecular mechanisms in cell signaling and gene expression; 2013

SAIB

We have previously shown that 1á,25(OH)2-Vitamin D3 [1á,25(OH)2D3] and its less calcemic analog TX 527 inhibit the proliferation of endothelial cells (SVEC) and transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR) through NFkB inhibition and inducing apoptosis via caspase-3 activation. The intrinsic apoptotic pathway could be activated by mitochondrial disruption changing the balance between pro and antipoptotic proteins. In the present work we study the expression of pro and antiapoptic proteins Bcl-2, Bax and Bim at mRNA and protein levels in SVEC and vGPCR cells stimulated by 1á,25(OH)2D3 and TX 527. Time response qRT-PCR analysis of anti apoptotic protein Bcl-2 demonstrated that mRNA levels decrease at 12 h and then increase at 48 h in 1á,25(OH)2D3 and TX 527-treated SVEC, whereas protein levels remain unchanged through time in both SVEC and vGPCR cells. Anti apoptotic protein Bax remain unchanged whereas Bim mRNA and its protein levels increased in SVEC cells. On the other hand, Bortezomib (0.5 µM), a proteasome inhibitor, similarly to vitamin D agonists, also increases Bim protein levels. Altogether these results suggest that 1á,25(OH)2D3 and TX 527 inhibit the NFkB pathway and trigger apoptosis inducing and increase in Bim protein that could elicit caspase -3 activation through the intrinsic apoptotic pathway in endothelial cells.