p44/42 ERK1/2 MAPK and PLD activation by PGD2 preserves papillary phosphatidylcholine homeostasis

FERNÁNDEZ-TOME, M; FAVALE, NO; KRAEMER, L; MARQUEZ, MG; SPEZIALE, E; STERIN-SPEZIALE NB

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Elsevier

Año: 2004 vol. 320 p. 1055 - 1062

0006-291X

Previous works from our laboratory demonstrated that PGD2 modulates phosphatidylcholine (PC) biosynthesis in renal papillary tissue. In the present work, we have evaluated the mechanism by which PGD2 exerts this action. PGD2 caused two stimulatory waves in PC synthesis which were reproduced by its full-agonist BW245C. At 1 min stimulation, PGD2 increased PC synthesis by 131%; this increase was blocked by neomycin and ethanol, cheleritrine and U0126, PLD, PKC, and MEK1/2 inhibitors, respectively. A second PC synthesis increase (100%) was observed after 15 min, which was blocked by PLD inhibitors. PGD2 also increased phospho-ERK1/2 MAPK in a biphasic-fashion, which was abolished by PLC and PKC inhibitors but not by ethanol, which overincreased phospho-ERK1/2, suggesting that PGD2-induced ERK1/2 activation requires previous PLC–PKC activation while PLD down-regulates it. Our results indicate that PGD2 stimulatory effect involves both PLD and ERK1/2-MAPK activation, and both pathways operate independently of PC synthesis homeostasis.