BUZZI Natalia Sol
congresos y reuniones científicas
Effects of PTH and 1a,25(OH)2-Vitamin D3 on JNK and p38 MAPK in rat Intestinal Cells
BUZZI, NATALIA SOL; GONZALES PARDO, VERÓNICA; RICARDO BOLAND,; RUSSO DE BOLAND, ANA
Congreso; Twenty-Seventh Annual Meeting of the American Society for Bone and Mineral Research; 2005
American Society for Bone and Mineral Research
Natalia Buzzi, Verónica Gonzalez Pardo, Ricardo Boland and Ana Russo de Boland. Depto. Biología, Bioquímica y Farmacia. Universidad Nacional del Sur. 8000 Bahia Blanca, Argentina. We have previously demonstrated that parathyroid hormone (PTH) and the steroid hormone 1,25(OH)2-vitamin D3 [1,25(OH)2D3] activate the cytosolic tyrosine kinase c-Src in rat intestinal cells (enterocytes), which, in turn, participates in the phosphorylation and activation of the MAP kinases ERK1 and ERK2. In the present study we examined whether these hormones are able to stimulate other members of the MAP kinases family. Our results show that, 1a,25(OH)2D3 induces the phosphorylation and activation of p38 MAPK in rat enterocytes. This effect was time and dose-dependent, with maximal stimulation at 2 min (+3 fold) and 1 nM. Opposite to the steroid hormone, PTH decreases, within 15 to 30 min, the basal phosphorylation and activity of p38 MAPK. 1,25(OH)2D3-dependent p38 phosphorylation was suppressed by SB 203580, a selective inhibitor of p38 MAPK. Ca2+ chelation with EGTA, inhibition of c-Src- family tyrosine kinase with PP1 or protein kinase A (PKA) inhibition with Rp-cAMP, attenuated hormone effects. Stimulation of rat enterocytes with 125(OH)2D3 (1 nM) or PTH (10 nM) also resulted in the phosphorylation and activation of c-jun N-terminal protein kinases (JNK 1/2). The effect of either hormone on JNK1/2 was transient, peaking at 1min (+200%) and 2 min (+300%) for 1,25(OH)2D3 and PTH , respectively. Incubation of enterocytes with 125(OH)2D3 was followed by a rapid induction of c-Fos expression (+1 fold, 5 min) which was blocked by SB 203580 and partially suppressed by the ERK1/2 inhibitor, PD 98059, while incubation with PTH did not altered the levels of the oncoprotein. Collectively, these data suggest that PTH and 1a25(OH)2D3 differentially regulate p38 MAPK and JNK1/2 in rat intestinal cells and that p38 MAPK has a central role in 1a25(OH)2D3-induction of the oncoprotein c-Fos.