Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein

Andrew D. Watson, Ganesamoorthy Subbanagounder, Derek S. Welsbie, Kym F. Faull, Mohamad Navab, Michael E. Jung, Alan M. Fogelman, Judith A. Berlinert

Research output: Contribution to journalArticle

Abstract

One of the earliest steps in the development of the atherosclerotic lesion is the accumulation of monocyte/macrophages within the vessel wall. Oxidized lipids present in minimally modified-low density lipoproteins (MM- LDL) contribute to this process by activating endothelial cells to express monocyte-specific adhesion molecules and chemoattractant factors. A major focus of our group has been the isolation and characterization of the biologically active oxidized lipids in MM-LDL. We have previously characterized three oxidized phospholipids present in MM-LDL, atherosclerotic lesions of fat fed rabbits, and autoxidized 1-palmitoyl-2-arachidonoyl-sn- glycero-3-phosphocholine (Ox-PAPC) that induced human aortic endothelial cells to adhere human monocytes in vitro. We have used sequential normal and reverse phase-high performance liquid chromatography to isolate various isomers of an oxidized phospholipid from autoxidized 1-palmitoyl-2- arachidonoyl-sn-glycero-3-phosphocholine. The fatty acid in the sn-2 position of this biologically active isomer and its dehydration product was released by phospholipase A2 and characterized. Hydrogenation with platinum(IV) oxide/hydrogen suggested a cyclic moiety, and reduction with sodium borohydride suggested two reducible oxygen-containing groups in the molecule. The fragmentation pattern produced by electrospray ionization-collision induced dissociation-tandem mass spectrometry was consistent with a molecule resembling an E-ring prostaglandin with an epoxide at the 5,6 position. The structure of this lipid was confirmed by proton nuclear magnetic resonance spectroscopy analysis of the free fatty acid isolated from the dehydration product of m/z 828.5. Based on these studies, we arrived at the structure of the biologically active oxidized phospholipids as 1-palmitoyl-2-(5,6- epoxyisoprostane E2)-sn-glycero-3-phosphocholine. The identification of this molecule adds epoxyisoprostanes to the growing list of biologically active isoprostanes.

Original languageEnglish (US)
Pages (from-to)24787-24798
Number of pages12
JournalJournal of Biological Chemistry
Volume274
Issue number35
DOIs
StatePublished - Aug 27 1999
Externally publishedYes

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Monocytes
Phospholipids
Lipids
Dehydration
Molecules
Endothelial cells
Endothelial Cells
Isomers
Isoprostanes
Phosphorylcholine
Hydrogenation
Phospholipases A2
Epoxy Compounds
Chemotactic Factors
Tandem Mass Spectrometry
Prostaglandins E
Focus Groups
LDL Lipoproteins
Nonesterified Fatty Acids
Electrospray ionization

ASJC Scopus subject areas

  • Biochemistry

Cite this

Watson, A. D., Subbanagounder, G., Welsbie, D. S., Faull, K. F., Navab, M., Jung, M. E., ... Berlinert, J. A. (1999). Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein. Journal of Biological Chemistry, 274(35), 24787-24798. https://doi.org/10.1074/jbc.274.35.24787

Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein. / Watson, Andrew D.; Subbanagounder, Ganesamoorthy; Welsbie, Derek S.; Faull, Kym F.; Navab, Mohamad; Jung, Michael E.; Fogelman, Alan M.; Berlinert, Judith A.

In: Journal of Biological Chemistry, Vol. 274, No. 35, 27.08.1999, p. 24787-24798.

Research output: Contribution to journalArticle

Watson, AD, Subbanagounder, G, Welsbie, DS, Faull, KF, Navab, M, Jung, ME, Fogelman, AM & Berlinert, JA 1999, 'Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein', Journal of Biological Chemistry, vol. 274, no. 35, pp. 24787-24798. https://doi.org/10.1074/jbc.274.35.24787
Watson, Andrew D. ; Subbanagounder, Ganesamoorthy ; Welsbie, Derek S. ; Faull, Kym F. ; Navab, Mohamad ; Jung, Michael E. ; Fogelman, Alan M. ; Berlinert, Judith A. / Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 35. pp. 24787-24798.
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AU - Navab, Mohamad

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