The cyclopentenone (A2/J2) isoprostanes--unique, highly reactive products of arachidonate peroxidation.
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.
Milne
Ginger L
GL
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Musiek
Erik S
ES
Morrow
Jason D
JD
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002849:Chromatography, Gas; D003517:Cyclopentanes / Q000737:chemistry*; D004281:Docosahexaenoic Acids / Q000737:chemistry; D015777:Eicosanoids / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D028421:Isoprostanes / Q000737:chemistry*; D015289:Leukotrienes / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D011454:Prostaglandins A / Q000737:chemistry; D013997:Time Factors; D017962:alpha-Linolenic Acid / Q000737:chemistry
D003517:Cyclopentanes; D015777:Eicosanoids; D005227:Fatty Acids; D028421:Isoprostanes; D015289:Leukotrienes; D008055:Lipids; D010545:Peroxides; D011454:Prostaglandins A; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D002244:Carbon; D011451:Prostaglandin-Endoperoxide Synthases; C100008:prostaglandin A2; C013905:cyclopentenone