PHOSPHATIDYLCHOLINE SYNTHESIS REGULATION BY PGD2 IS MEDIATED BY MAPK ACTIVATION

FERNÁNDEZ-TOME M; FAVALE N; SPEZIALE E; STERIN-SPEZIALE N

Bariloche , Rio Negro, Argentina

Congreso; XXXIX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2003

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Phosphatidylcholine (PC) is a main lipid of biomembranes with important structural and functional roles. In previous works, we have demonstrated that renal papillary PC synthesis is regulated by endogenous-synthesised prostaglandin D2 (PGD2) and that such regulation occurs on PC biosynthetic enzymes. The purpose of the present work was to evaluate the mechanism by which PGD2 exerts its modulatory action on PC synthesis. We first studied which receptor could be activated by PGD2 interaction and found that sulprostone (a PGE2 receptor, EP3 full-agonist) mimicked the effect of PGD2 on PC synthesis. Hence, we studied if MAPK activation, which was reported to be involved in EP3 actions, was mediating PGD2 regulatory action on papillary PC synthesis. Thus, we evaluated renal papillary PC biosynthesis as 32Pi incorporation to PC in the absence or in the presence of PGD2 with or without the addition of U0126, a selective MEK inhibitor. We found that PGD2 induced MAPK-phosphorylation which was prevented by U0126. This inhibitor also blocked the PGD2 effect on PC biosynthesis with the same pattern observed for MAPK activation, thus suggesting the involvement of this pathway in the maintenance of PC synthesis in renal papillary membranes.