“Activation of MAPKs by 1,25(OH)2-vitamin D3 in proliferating skeletal muscle cells involves the participation of caveolin-1”

BUITRAGO C; BOLAND R

Córdoba

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2008

SAIB

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES; mso-fareast-language:ES;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> 1a,25(OH)2D3 is a steroid hormone that regulates intracellular signals in various cell types. The ERK1/2 and p38, members of MAPK family are signaling pathways which mediate rapid responses to extracellular stimuli. There are data of 1a,25(OH)2D3 -modulation of MAPKs in skeletal muscle cells, but the role of caveolae components in the fast effects of the hormone in this tissue have not been investigated. In the present work, using the skeletal muscle cell line C2C12 in proliferative stage, we demonstrate by Western blot that 1a,25(OH)2D3 –dependent ERK1/2 and p38 phosphorylation and c-Src activation are suppressed by disassembling caveolae with methyl-beta cyclodextrin (MbCD). Caveolin-1 (cav-1) is a molecule of caveolae in this cellular type. Therefore, we investigated the relationship between cav-1 and c-Src. Immunocytochemical assays showed a basal cav-1 and c-Src colocalization at plasma membrane. 1a,25(OH)2D3 abolished colocalization of cav-1 and c-Src only in absence of MbCD. Localization of the vitamin D receptor (VDR) in these cells was investigated. Congruent with previous results, translocation of the VDR to the plasma membrane occurs in cells treated with 1a,25(OH)2D3. In cells exposed to MbCD the VDR is present only in the nucleus. These data suggest that caveolae are involved in c-Src–dependent MAPK activation by 1a,25(OH)2D3 through the VDR in skeletal muscle cells.