CALCITRIOL AND 17b-ESTRADIOL-DEPENDENT ACTIVATION OF MAPKs IN SKELETAL MUSCLE CELLS: ROLE OF Elk-1 AND CREB

RONDA ANA CAROLINA; BUITRAGO CLAUDIA; COLICHEO ANDREA; RUSSO DE BOLAND ANA; BOLAND RICARDO

PINAMAR, BUENOS AIRES, ARGENTINA

Congreso; SAIB XLI REUNIÓN ANUAL; 2005

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR

The mitogen activated protein kinases (MAPKs) have been classified into at least six subfamilies, among which ERK1/2, JNK1/2 and p38 MAPK are the most extensively studied. Whereas ERK1/2 is considered to respond to growth signals, JNK1/2 and p38 are activated by cellular stresses. In various cell types, calcitriol (1a,25-dihydroxy-vitamin D3) and 17b-estradiol promote biological responses through activation of MAPK cascades. We have previously shown that calcitriol stimulates muscle cell proliferation via ERK1/2. In this work, using as experimental model the skeletal muscle cell line C2C12, we demonstrate that calcitriol and 17b-estradiol phosphorylate and activate ERK1/2 and p38 MAPK, in a time-dependent fashion. Maximal effects were seen at 90 and 30 min (ERK1/2) and at 60 and 15 min (p38 MAPK) for calcitriol and 17b-estradiol, respectively. Calcitriol and 17b-estradiol also induced the phosphorylation of CREB and Elk-1 transcription factors in an ERK1/2-dependent manner. Simultaneous addition of both hormones potentiated CREB phosphorylation. Of relevance, Elk-1 phosphorylation dependent on either hormone, was correlated with c-fos oncoprotein expression. These results demonstrate that the ERK1/2 and p38 MAPK signalling pathways play an important role in regulating immediate early genes in the skeletal muscle line C2C12.