Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgamma.
Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgamma.
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15-脱氧-delta12,14-PGJ2 的生物合成和 PPARgamma 的连接。
DOI：
10.1172/jci18012
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
FitzGerald,GarretA
中科院分区：
文献类型：
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作者：
Bell-Parikh,LChastine;Ide,Tomomi;Lawson,JohnA;McNamara,Peter;Reilly,Muredach;FitzGerald,GarretA
15-deoxy-Δ12,14-PGJ2(15d-PGJ2) 已被确定为 PPARγ 的内源性配体，可在体外诱导脂肪形成。已经提出该分子在炎症的传播和消退、NF-κB 连接以及细胞凋亡介导中的其他作用。然而，缺乏体内 15d-PGJ2 形成的定量、理化证据。我们报告使用液相色谱-质谱-质谱法可在 3T3-L1 前脂肪细胞培养基中以低皮摩尔浓度检测到 15d-PGJ2。然而，尽管诱导了 COX-2，但在脂肪细胞分化过程中，PG（包括 15d-PGJ2）的产生并没有增加，这一过程不受 COX 抑制的影响。 15d-PGJ2 可作为人尿液中 COX-2 的次要产物进行检测。然而，在体内 COX 被 LPS 激活期间或之后，其生物合成并未改变。此外，关节炎患者关节液中 15d-PGJ2 的生物合成并没有增加，糖尿病或肥胖患者的尿排泄也没有增加。 15d-PGJ2 不是 PPARγ 依赖性脂肪细胞激活的内源性介质，并且在涉及 PPARγ 激活的临床环境中不会发生改变。
15-deoxy-Δ12,14-PGJ2(15d-PGJ2) has been identified as an endogenous ligand for PPARγ, inducing adipogenesis in vitro. Additional roles for this molecule in the propagation and resolution of inflammation, ligation of NF-κB, and mediation of apoptosis have been proposed. However, quantitative, physiochemical evidence for the formation of 15d-PGJ2in vivo is lacking. We report that 15d-PGJ2is 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-PGJ2is 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-PGJ2is not augmented in the joint fluid of patients with arthritis, nor is its urinary excretion increased in patients with diabetes or obesity. 15d-PGJ2is not the endogenous mediator of PPARγ-dependent adipocyte activation and is unaltered in clinical settings in which PPARγ activation has been implicated.