INVESTIGADORES
BUITRAGO Claudia Graciela
congresos y reuniones científicas
Título:
.Participación de caveolina-1 en la regulación de c-Src, cascadas MAPKS y localización del VDR por 1,25(OH)2-vitamina D3 en células musculares esqueléticas.
Autor/es:
BUITRAGO C; BOLAND R
Lugar:
Buenos Aires
Reunión:
Congreso; XXVI Reunion Annual Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2009
Resumen:
<!--
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-parent:"";
margin:0cm;
margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:12.0pt;
mso-bidi-font-size:10.0pt;
font-family:"Times New Roman";
mso-fareast-font-family:"Times New Roman";
mso-ansi-language:EN-US;
mso-fareast-language:ES;}
p.MsoBodyText, li.MsoBodyText, div.MsoBodyText
{margin:0cm;
margin-bottom:.0001pt;
line-height:150%;
mso-pagination:widow-orphan;
font-size:12.0pt;
mso-bidi-font-size:10.0pt;
font-family:"Times New Roman";
mso-fareast-font-family:"Times New Roman";
mso-ansi-language:EN-US;
mso-fareast-language:ES;
font-weight:bold;
mso-bidi-font-weight:normal;}
@page Section1
{size:612.0pt 792.0pt;
margin:70.85pt 3.0cm 70.85pt 3.0cm;
mso-header-margin:36.0pt;
mso-footer-margin:36.0pt;
mso-paper-source:0;}
div.Section1
{page:Section1;}
-->
Previously, we demonstrated that 1a,25-dihydroxi-vitamin D3 [1a,25(OH)2D3] induces non-transcriptional rapid
responses through activation of MAPKs in the skeletal muscle cell
line C2C12. However, there is no information on the molecular mechanism
underlying the initiation of 1a,25(OH)2D3 signaling through these
pathways.
Lipid
raft components have been involved in steroid non-genomic effects. In this work
we investigated the role of caveolae and caveolin-1 (cav-1) in phosphorylation
of MAPKs and c-Src activation by 1a,25(OH)2D3. When proliferating
C2C12 cells were pre-treated with methyl-beta-cyclodextrin (MbCD), a
caveolae disrupting agent, under conditions in which cell morphology is not
affected and no signs of apoptosis are observed, 1a,25(OH)2D3-dependent
activation of ERK 1/2, p38 MAPK and c-Src was suppressed. Similar results were
obtained by siRNA technology where silencing of cav-1 expression abolished
phosphorylation of MAPKs and c-Src induced by 1a,25(OH)2D3.
Confocal immunocytochemistry and co-immunoprecipitation assays showed that
cav-1 colocalizes with c-Src in the periplasma membrane zone at basal
conditions. Hormone treatment redistributed these proteins into cytoplasm and
nucleus and disrupted their colocalization. Confocal microscopy also revealed that
1a,25(OH)2D3
induces translocation of the VDR to the plasma membrane in C2C12 cells,
and this effect is abolished by MbCD. Preliminary studies suggested a 1a,25(OH)2D3-dependent VDR-c-Src association. Altogether, these
data indicate that intact caveolae participate in an early upstream step in 1a,25(OH)2D3
signal transduction via c-Src-MAPKs and that the VDR and cav-1 are involved in
the rapid events triggered by the hormone in skeletal muscle cells.
