科研之友
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摘要
15-Deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) is a reactive cyclopentenone eicosanoid generated from the dehydration of cyclooxygenase-derived prostaglandin D-2 (PGD(2)). This compound possesses an alpha,beta-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-PGJ(2) is thought to modulate inflammatory and apoptotic processes and is believed to be an endogenous ligand for peroxisome proliferator-activated receptor-gamma. However, the extent to which 15-d-PGJ(2) is formed in vivo and the mechanisms that regulate its formation are unknown. Previously, we have reported the formation of PGD(2) and PGJ(2)-like compounds, termed D-2/J(2)-isoprostanes (D-2/J(2)-IsoPs), produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid (AA). Based on these findings, we investigated whether 15-d-PGJ(2)-like compounds are also formed via this nonenzymatic pathway. Here we report the generation of novel 15-d-PGJ(2)-like compounds, termed deoxy-J(2)-isoprostanes (deoxy-J(2)-IsoPs), in vivo, via the nonenzymatic peroxidation of AA. Levels of deoxy-J(2)-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.-Hardy, K. D., B. E. Cox, G. L. Milne, H. Yin, and L. Jackson Roberts II. Nonenzymatic free radical-catalyzed generation of 15-deoxy-Delta(12,14)-prostaglandin J2-like compounds (deoxy-J2-isoprostanes) in vivo. J. Lipid Res. 2011. 52: 113-124
- 出版日期2011-1
