Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgamma.
J Clin Invest
; 112(6): 945-55, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-12975479
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Complementares:
Homeopatia
Assunto principal:
Fatores de Transcrição
/
Prostaglandina D2
/
Receptores Citoplasmáticos e Nucleares
/
Fatores Imunológicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos