VDR expression is required in 1?Ñ,25(OH)2-vitamin D3- rapid actions in skeletal muscle cells

BUITRAGO C; BOLAND R

Mendoza

Congreso; SAIB; 2012

1a,25(OH)2-vitamin D3 [1,25D] is a steroid hormone that produces biologic effects via both genomic and nongenomic pathways in skeletal muscle cells. The genomic responses occur through its binding with the vitamin D receptor (VDR). However, there is no information about the molecules involved in the initiation of rapid-nongenomic events. In our laboratory, we have previously demonstrated the stimulation of MAPKs through c-Src by 1,25D in skeletal myoblasts. Moreover, we reported that caveolae components mediate the fast effects of the hormone in the skeletal muscle cell line C2C12. In this work we obtained data indicating that the VDR is required in the non-genomic action of 1,25D. We knocked down (80%) vitamin D receptor expression transfecting C2C12 cells with 2 shRNAs against VDR. In these cells (VDR-) Western blot analysis show that 1,25D-induced Src activation and p38 phosphorylation are suppressed. In addition, ERK1/2 and Akt activation are also dependent on VDR expression in C2C12 skeletal muscle cells. These data evidence for first time that the VDR is involved in rapid events triggered by 1a,25(OH)2D3 in skeletal muscle cells, providing relevant information on the mechanism of initiation of the non-genomic hormone signal.