1a,25(OH)2- VITAMIN D3 STIMULATES INTESTINAL CELL P38 MAPK ACTIVITY AND IMMEDIATE-EARLY GENE EXPRESION

GONZALEZ PARDO, MARIA VERONICA; RUSSO DE BOLAND, ANA

San Diego

Congreso; Experimental Biology 2005 Annual Meeting; 2005

ASBMB

The stress-activated protein kinase p38 MAPK has been shown to be expressed in intestinal tissues and to play a role in regulating a variety of intestinal processes, including epithelial restitution, cytoskeletal organization and ion transport. In the present study, we have demonstrated that the hormone 1a,25(OH)2-vitaminD3 [1,25(OH)2D3] induces the phosphorylation and activation of p38 MAPK in rat intestinal cells. This effect was dose and time-dependent, with maximal stimulation at 2 min (+3 fold) and 1 nM. Calcium chelation with EGTA or BAPTA-AM, inhibition of the Src-family tyrosine kinase with PP1 or PKA inhibition with  Rp-cAMP, attenuated hormone-dependent p38 phosphorylation. The physiological significance of 1,25(OH)2D3-dependent activation of MAP kinases was addressed by monitoring c-fos expression in intestinal cells. Incubation of the cells with the hormone was followed by rapid induction of c-fos expression (+1 fold, 5 min) which was blocked by the p38 inhibitor SB203580 and partially suppressed by the ERK1/2 inhibitor, PD 98059. Taken together, our results suggest that 1,25(OH)2D3 activates p38 MAPK, involving  Calcium,  c-Src and PKA as upstream regulators and that p38 has a central rol in the hormone-induction of the oncoprotein c-fos in rat intestinal cells.