ACTIVATION OF MAPKS BY 1a25(OH)2-VITAMIN D3 AND 17b-ESTRADIOL IN SKELETAL MUSCLE CELLS LEADS TO PHOSPHORYLATION OF ELK-1 AND CREB TRANSCRIPTION FACTORS

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

VICTORIA

Workshop; 13TH WORKSHOP ON VITAMIN D; 2006

WORKSHOP VITAMNI D

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. The steroid hormones 1a,25-dihydroxy-vitamin D3 and 17b-estradiol promote biological responses through activation of MAPK cascades in various cell types. We previously reported that 1a,25(OH)2D3 rapidly (within 1 min) activates p38 MAPK in C2C12 muscle cells. In this work, using the same muscle cell line, we demonstrate that 1a,25(OH)2D3 or 17b-estradiol phosphorylate and activate ERK1/2 and p38 MAPK after longer treatment intervals, maximal effects seen at 90 and 30 min (ERK1/2) and at 60 and 15 min (p38 MAPK) for these hormones, respectively. Hormone-dependent ERK and p38 activation was abolished by MAPK specific inhibitors U0126 and SB203580. 1a,25(OH)2D3 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. 1a,25(OH)2D3 and 17b-estradiol-induced c-fos expression, that was dependent on p38 phosphorylation. The action of 17b-estradiol on c-fos levels was also mediated by ERK1/2. These results suggest that MAPK signalling pathways play an important role in regulating early gene expression through CREB and Elk-1 activation in skeletal muscle cells.