出版社：American Society for Biochemistry and Molecular Biology
摘要：15-Deoxy-Δ12,14-prostaglandin J2 (15-d-PGJ2) is a reactive cyclopentenone eicosanoid generated from the dehydration of cyclooxygenase-derived prostaglandin D2 (PGD2). This compound possesses an α,β-unsaturated carbonyl moiety that can readily adduct thiol-containing biomolecules such as glutathione and cysteine residues of proteins via the Michael addition. Due to its reactivity, 15-d-PGJ2 is thought to modulate inflammatory and apoptotic processes and is believed to be an endogenous ligand for peroxisome proliferator-activated receptor-γ. However, the extent to which 15-d-PGJ2 is formed in vivo and the mechanisms that regulate its formation are unknown. Previously, we have reported the formation of PGD2 and PGJ2-like compounds, termed D2/J2-isoprostanes (D2/J2-IsoPs), produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid (AA). Based on these findings, we investigated whether 15-d-PGJ2-like compounds are also formed via this nonenzymatic pathway. Here we report the generation of novel 15-d-PGJ2-like compounds, termed deoxy-J2-isoprostanes (deoxy-J2-IsoPs), in vivo, via the nonenzymatic peroxidation of AA. Levels of deoxy-J2-IsoPs increased 12-fold (6.4 ± 1.1 ng/g liver) in rats after oxidant insult by CCl4 treatment, compared with basal levels (0.55 ± 0.21 ng/g liver). These compounds may have important bioactivities in vivo under conditions associated with oxidant stress.
