“ACTIVATION OF MAPKs BY CALCITRIOL AND 17b-ESTRADIOL IN SKELETAL MUSCLE CELLS LEADS TO PHOSPHORYLATION OF ELK-1 AND CREB TRANSCRIPTION FACTORS”.

RONDA A C; BUITRAGO C; COLICHEO A; RUSSO DE BOLAND A; BOLAND R

Victoria British Columbia, Canadá

Workshop; 13th Vitamin D Workshop; 2006

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, but the response of these kinases are cellular tissue-dependent. Calcitriol (1a,25-dihydroxy-vitamin D3) and 17b-estradiol are steroid hormones that promote biological responses through activation of MAPK cascades in various cell types. We previously reported 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 separately 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) these hormones, respectively. The specific inhibitors U0126 and SB203580 abolished ERKs and p38 activation 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. The 17b-estradiol- induced c-fos expression was dependent on p38 phosphorylation. These results demonstrate that the MAPKs signalling pathways play an important role in regulating immediate early genes in the skeletal muscle line C2C12.