Straus D S, Glass C K
Biomedical Sciences Division and Biology Department, University of California, Riverside, CA 92521-0121, USA.
Med Res Rev. 2001 May;21(3):185-210. doi: 10.1002/med.1006.
The cyclopentenone prostaglandins PGA2, PGA1, and PGJ2 are formed by dehydration within the cyclopentane ring of PGE2, PGE1, and PGD2. PGJ2 is metabolized further to yield Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). Various compounds within the cyclopentenone prostaglandin family possess potent anti-inflammatory, anti-neoplastic, and anti-viral activity. Most actions of the cyclopentenone prostaglandins do not appear to be mediated by binding to G-protein coupled prostanoid receptors. Rather, the bioactivity of these compounds results from their interaction with other cellular target proteins. 15-deoxy-Delta(12,14)-PGJ(2) is a high affinity ligand for the nuclear receptor PPARgamma and modulates gene transcription by binding to this receptor. Other activities of the cyclopentenone prostaglandins are mediated by the reactive alpha,beta-unsaturated carbonyl group located in the cyclopentenone ring. The transcription factor NF-kappaB and its activating kinase are key targets for the anti-inflammatory activity of 15d-PGJ2, which inhibits NF-kappaB-mediated transcriptional activation by PPARgamma-dependent and independent molecular mechanisms. Other cyclopentenone prostaglandins, such as Delta(7)-PGA1 and Delta(12)-PGJ2, have strong anti-tumor activity. These compounds induce cell cycle arrest or apoptosis of tumor cells depending on the cell type and treatment conditions. We review here recent progress in understanding the mechanisms of action of the cyclopentenone prostaglandins and their possible use as therapeutic agents.
环戊烯酮前列腺素PGA2、PGA1和PGJ2是由PGE2、PGE1和PGD2的环戊烷环脱水形成的。PGJ2进一步代谢生成Δ(12)-PGJ(2)和15-脱氧-Δ(12,14)-PGJ(2)（15d-PGJ(2)）。环戊烯酮前列腺素家族中的各种化合物具有强大的抗炎、抗肿瘤和抗病毒活性。环戊烯酮前列腺素的大多数作用似乎不是通过与G蛋白偶联前列腺素受体结合介导的。相反，这些化合物的生物活性源于它们与其他细胞靶蛋白的相互作用。15-脱氧-Δ(12,14)-PGJ(2)是核受体PPARγ的高亲和力配体，通过与该受体结合来调节基因转录。环戊烯酮前列腺素的其他活性由位于环戊烯酮环中的反应性α,β-不饱和羰基介导。转录因子NF-κB及其激活激酶是15d-PGJ2抗炎活性的关键靶点，15d-PGJ2通过PPARγ依赖性和非依赖性分子机制抑制NF-κB介导的转录激活作用。其他环戊烯酮前列腺素，如Δ(7)-PGA1和Δ(12)-PGJ2，具有很强的抗肿瘤活性。这些化合物根据细胞类型和处理条件诱导肿瘤细胞的细胞周期停滞或凋亡。我们在此综述了在理解环戊烯酮前列腺素作用机制及其作为治疗剂的潜在用途方面的最新进展。
