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Isoprostane Activation of the Nuclear Hormone Receptor Ppar

  • Peter McNamara
  • John A. Lawson
  • Joshua Rokach
  • Garret A. FitzGerald
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)

Abstract

Isoprostanes (iPs) are chemically stable prostaglandin isomers that are generated by a free radical-catalyzed peroxidation of arachidonic acid. They include all members of prostaglandin classes and are generated initially in cell membranes at the site of free radical attack’. They are cleaved, presumably by phospholipases, circulate in plasma, and are excreted in urine2. F2-iPs are isomers of PGF2a a natural product derived from COX and PGF synthase. Depending on the site of the original arachidonyl radical formed; four groups of regioisomers of the F2-iPs may be produced upon rearrangement, oxygenation and reduction3. Given the mechanism of their formation and clearance, isoprostanes may reflect lipid peroxidation at the tissue site of free-radical generation or in body fluids like plasma and urine. Altered generation of iPs has been reported in a wide variety of syndromes putatively associated with oxidative stress including ischemia reperfusion syndromes4, atherosclerosis5 and Altzheimers disease6. The iPs are elevated in human atherosclerotic plaques’, where they are localized to monocyte/macrophages and smooth muscle cells, in circulating low density lipoprotein as well as in the urine of hypercholesterolemic subjects8. While reflecting lipid peroxidation in vivo they also act as specific and saturable incidental ligands for membrane prostaglandin receptors9. Suppression of elevated iPs retards atherogenesis and reverses established atherosclerosis in hypercholesterolemic mice10

Keywords

Free Radical Attack PPAR Isoforms American Type Tissue Culture Collection Ischemia Reperfusion Syndromes4 Human Aortic SMCs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Peter McNamara
    • 1
  • John A. Lawson
    • 1
  • Joshua Rokach
    • 2
  • Garret A. FitzGerald
    • 1
  1. 1.Center for Experimental TherapeuticsUniversity of PennsylvaniaPhiladelphiaPA
  2. 2.Florida Institute of TechnologyClaude Pepper Institute and Department of ChemistryMelbourne

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