p44/42(ERK1/2) MAPK and PLD activation by PGD2 preserves papillary phosphatidylcholine homeostasis.
Previous works from our laboratory demonstrated that PGD(2) modulates phosphatidylcholine (PC) biosynthesis in renal papillary tissue. In the present work, we have evaluated the mechanism by which PGD(2) exerts this action. PGD(2) caused two stimulatory waves in PC synthesis which were reproduced by its full-agonist BW245C. At 1min stimulation, PGD(2) 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 15min, which was blocked by PLD inhibitors. PGD(2) 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 PGD(2)-induced ERK1/2 activation requires previous PLC-PKC activation while PLD down-regulates it. Our results indicate that PGD(2) stimulatory effect involves both PLD and ERK1/2-MAPK activation, and both pathways operate independently of PC synthesis homeostasis.
Fernández-Tome
María
M
Faculty of Pharmacy and Biochemistry, Department of Biological Sciences, University of Buenos Aires, IQUIFIB-CONICET Ciudad de Buenos Aires (1113), Argentina.
Favale
Nicolás
N
Kraemer
Leticia
L
Gabriela Márquez
María
M
Speziale
Emir
E
Sterin-Speziale
Norma
N
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D046508:Culture Techniques; D004789:Enzyme Activation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010739:Phospholipase D / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010713:Phosphatidylcholines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010739:Phospholipase D; D015230:Prostaglandin D2