title: Role of VDR in 1α,25-dihydroxyvitamin D3-dependent non-genomic activation of MAPKs, Src and Akt in skeletal muscle cells.
abstract: 1α,25-dihydroxyvitamin D3 [1,25D] is recognized as a steroid hormone that rapidly elicits intracellular signals in various tissues. In skeletal myoblasts, we have previously demonstrated that one of the 1,25D-induced non-genomic effects is the upstream stimulation of MAPKs through Src activation. In this work, the data obtained suggest that the classical receptor of vitamin D (VDR) participates in non-transcriptional actions of 1,25D. We significantly reduced VDR expression by infection of C2C12 murine myoblasts with lentiviral particles containing the pLKO.1 plasmid with information to express a shRNA against mouse VDR. In these cells (C2C12-shVDR), Western blot analyses show that 1,25D-induced p38 MAPK activation and Src tyr416 phosphorylation were abolished. In addition, 1,25D-dependent activity of ERK1/2 was diminished in cells lacking VDR but to a lesser extent (∼-60%). Phosphorylation of Akt by 1,25D, recently demonstrated in C2C12 cells, in the present work also appeared to be partially dependent on VDR expression (∼50% in C2C12-shVDR cells). Our results indicate that VDR is involved in 1,25D-induced rapid events related to survival/proliferation responses in skeletal muscle cells, providing relevant information on the mechanism of initiation of the non-genomic hormone signal. The participation of a VDR-independent non-genomic mechanism of action should also be taken into consideration. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
authors.affiliation: Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, 8000 Bahía Blanca, Argentina. cbuitrag@criba.edu.ar
authors.forename: Claudia
authors.initials: C
authors.lastname: Buitrago
authors.forename: Verónica Gonzalez
authors.initials: VG
authors.lastname: Pardo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Boland
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D002117:Calcitriol