Milne Ginger L, Musiek Erik S, Morrow Jason D
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):210-20. doi: 10.1089/ars.2005.7.210.
Cyclopentenone (A2/J2) isoprostanes (IsoPs) are a group of prostaglandin (PG)-like compounds generated in vivo from the free radical-induced peroxidation of arachidonic acid. Unlike other classes of IsoPs, cyclopentenone IsoPs contain highly reactive unsaturated carbonyl moieties on the prostane ring analogous to cyclooxygenase-derived PGA2 and PGJ2 that readily adduct relevant biomolecules such as thiols via Michael addition. The purpose of this review is to summarize our knowledge of the A2/J2-IsoPs. As a starting point, we will briefly discuss the formation and biological properties of PGA2 and PGJ2. Next, we will review studies definitively showing that cyclopentenone IsoPs are formed in large amounts in vivo. This is in marked contrast to cyclopentenone PGs, for which little evidence exists that they are endogenously produced. Subsequently, we will discuss studies related to the chemical syntheses of the 15-A2-IsoP series of cyclopentenone IsoPs. The successful synthesis of these compounds provides the recent impetus to explore the metabolism and biological properties of A-ring IsoPs, particularly as modulators of inflammation, and this work will be discussed. Finally, the formation of cyclopentenone IsoP-like compounds from other fatty acids such as linolenic acid and docosahexaenoic acid will be detailed.
环戊烯酮（A2/J2）异前列腺素（IsoPs）是一类在体内由自由基诱导花生四烯酸过氧化而产生的类前列腺素（PG）化合物。与其他类别的IsoPs不同，环戊烯酮IsoPs在前列腺素环上含有高度反应性的不饱和羰基部分，类似于环氧化酶衍生的PGA2和PGJ2，它们可通过迈克尔加成轻易地与相关生物分子如硫醇加合。本综述的目的是总结我们对A2/J2-IsoPs的认识。作为起点，我们将简要讨论PGA2和PGJ2的形成及生物学特性。接下来，我们将回顾明确表明环戊烯酮IsoPs在体内大量形成的研究。这与环戊烯酮PGs形成显著对比，几乎没有证据表明它们是内源性产生的。随后，我们将讨论与15-A2-IsoP系列环戊烯酮IsoPs化学合成相关的研究。这些化合物的成功合成推动了近期对A环IsoPs代谢和生物学特性的探索，特别是作为炎症调节剂，这方面的工作也将进行讨论。最后，将详细阐述由其他脂肪酸如亚麻酸和二十二碳六烯酸形成环戊烯酮IsoP样化合物的过程。
