15-Deoxy-delta12,14-PGJ2: endogenous PPARgamma ligand or minor eicosanoid degradation product?

Abstract

15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) affects gene transcription by activating PPARgamma and by covalent addition to transcription factors and signaling molecules, However, it is not known whether the high concentrations of 15d-PGJ2 required for these responses are consistent with physiological levels. A new study suggests that in vivo 15d-PGJ2 levels are actually several orders of magnitude below the levels required to induce many of the biological effects attributed to this molecule.

Figure 1

Formation of 15d-PGJ₂ and its effects on receptors and signaling molecules. The degradation of PGD₂ to 15d-PGJ₂ is enhanced by albumin. In addition to its effects on intracellular proteins, 15d-PGJ₂ also activates the DP₂ receptor. PGD₂ can also be metabolized enzymatically (Enz) to 11β-PGF_2α and 13,14-dihydro-15-keto-PGD₂ (dhk-PGD₂). The latter metabolite also activates the DP₂ receptor. Some of the effects of 15d-PGJ₂ on intracellular proteins are mediated by Michael addition to the reactive cyclopentenone ring (box). In contrast to its effect on the DP₂ receptor, 15d-PGJ₂ does not activate the DP₁ receptor.