Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgamma.
15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) has been identified as an endogenous ligand for PPARgamma, inducing adipogenesis in vitro. Additional roles for this molecule in the propagation and resolution of inflammation, ligation of NF-kappaB, and mediation of apoptosis have been proposed. However, quantitative, physiochemical evidence for the formation of 15d-PGJ2 in vivo is lacking. We report that 15d-PGJ2 is detectable using liquid chromatography-mass spectrometry-mass spectrometry at low picomolar concentrations in the medium of 3T3-L1 preadipocytes. However, despite induction of COX-2, production of PGs, including 15d-PGJ2, does not increase during adipocyte differentiation, a process unaltered by COX inhibition. 15d-PGJ2 is detectable as a minor product of COX-2 in human urine. However, its biosynthesis is unaltered during or after COX activation in vivo by LPS. Furthermore, the biosynthesis of 15d-PGJ2 is not augmented in the joint fluid of patients with arthritis, nor is its urinary excretion increased in patients with diabetes or obesity. 15d-PGJ2 is not the endogenous mediator of PPARgamma-dependent adipocyte activation and is unaltered in clinical settings in which PPARgamma activation has been implicated.
Bell-Parikh
L Chastine
LC
Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104-6084, USA. garret@spirit.gcrc.upenn.edu
Ide
Tomomi
T
Lawson
John A
JA
McNamara
Peter
P
Reilly
Muredach
M
FitzGerald
Garret A
GA
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001168:Arthritis / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000652:urine; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008024:Ligands; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins; D051379:Mice; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013582:Synovial Fluid / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D007527:Isoenzymes; D008024:Ligands; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone; D015230:Prostaglandin D2