INVESTIGADORES
RONDA Ana Carolina
congresos y reuniones científicas
Título:
MAP KINASES p38 AND JNK ARE ACTIVATED BY THE STEROID HORMONE 1a25(OH)2D3 IN THE C2C12 MUSCLE CELL LINE
Autor/es:
CLAUDIA BUITRAGO; ANA CAROLINA RONDA; ANA RUSSO DE BOLAND; RICARDO BOLAND
Lugar:
NASHVILLE, TENNESSEE, USA
Reunión:
Congreso; ASBMR 27TH ANNUAL MEETING; 2005
Institución organizadora:
AMERICAN SOCIETY FOR BONE AND MINERAL RESEACH
Resumen:
In chick skeletal muscle cell primary cultures we previously demostrated that 1a,25(OH)2-vitamin D3 [1A,25(OH)2D3], the hormonally active form of vitamin D, increases the phosphorylation and activity of the extracellular signal-regulated mitogen-activated protein (MAP) kinase isoforms ERK1 and ERK2, their subsequent translocation to the nucleus and involvement in DNA synthesis stimulation. In this study we show that other members of the MAP kinase superfamily are also activated by the hormone. Using the muscle cell line C2C12 we found that 1a,25(OH)2D3 within 1 min phosphorylates and increases the activity of p38 MAPK. The immediately upstream kinases MKK3/MKK6 were also phosphorylated by the hormone suggesting their participation in p38 activation. 1a,25(OH)2D3 was able to dephosphorylate/activate the ubiquitous cytosolic tyrosine kinase c-Src in C2C12 cells and studies with specific inhibitors imply that Src participates in hormone induced-p38 activation. Of relevance, 1a,25(OH)2D3 induced in the C2C12 line the stimulation of MAPKAP-kinase 2 and subsequent phosphorylation of HSP27 in a p38 kinase activation dependent manner. Treatment with the p38 inhibitor, SB203580, blocked p38 phosphorylation caused by the hormone and inhibit the phosphorylation of its downstream substrates. 1a,25(OH)2D3 also promotes the phosphorylation of c-jun N-terminal protein kinases (JNK 1/2), the response is fast (0.5-1 min.) and maximal phosphorylation of the enzyme is observed at physiological doses of 1a,25(OH)2D3 (1 nM). The relative contribution of ERK-1/2, p38 and JNK-1/2 and their interrelationships in hormonal regulation of muscle cell proliferation and differentiation remain to be established.