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Lipid peroxidation in low density lipoproteins from human plasma and egg yolk promotes accumulation of 1-acyl analogues of platelet-activating factor-like lipids

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Lipids

Abstract

Oxidative modification of low density lipoprotein (LDL) is known to be a key event for induction of atherosclerosis. However, there has been little progress in structural elucidation of oxidized lipids, especially oxidatively fragmented phospholipids retaining a glycerol backbone. In this study, we found that LDL derived from egg yolk has no platelet-activating factor (PAF) acetylhydrolase activity, and that prolonged incubation of egg yolk LDL with Cu2+ resulted in the formation of various PAF-like lipids: 1-acyl type phosphatidylcholines with ansn-2-short-chain dicarboxylate or monocarboxylate group. Only a very small amount of the PAF-like lipid having ansn-2-short-chain monocarboxylate group was detected by gas chromatography-mass spectrometry in Cu2+-oxidized LDL from human plasma with high PAF-acetylhydrolase activity, which has been reported to hydrolyze PAF-like lipids to lysophosphatidylcholines. Preincubation of plasma LDL with diisopropyl fluorophosphate dose-dependently inhibited PAF-acetylhydrolase activity, resulting in accumulation of the PAF-like lipids when the LDL was oxidized with Cu2+. As well as PAF and lysophosphatidylcholines, several PAF-like lipids were found to inhibit [3H]thymidine incorporation into cultured vascular smooth muscle cells derived from rat aorta. The possible formation of PAF-like lipids by lipid peroxidation in LDL is discussed as well as its possible significance for induction of atherosclerosis.

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Abbreviations

acylPAF:

1 long-chain acyl analogue of platelet- activating factor

BSA:

bovine serum albumin

DC:

short-chain dicarboxylate

DFP:

diisopropyl fluorophosphate

FAB-MS:

fast atom bombardment-mass spectrometry

GC-MS:

gas chromatography-mass spectrometry

GLC:

gas-liquid chromatography

GPC:

sn-glycero-3-phosphocholine

LDL:

low density lipoprotein

lysoPAF:

lysoplatelet-activating factor

lysoPC:

lysophosphatidylcholine

MC:

short-chain monocarboxylate

PAF:

platelet-activating factor

PAF-AH:

platelet-activating factor acetylhydrolase

PC:

phosphatidylcholine

tBDMS:

tert-butyldimethylsilyl

TLC:

thin-layer chromatography

VSMC:

vascular smooth muscle cells

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, the University of Tokushima, 1-78, Shomachi, 770, Tokushima, Japan

    Akira Tokumura, Masaoki Toujima, Yasuko Yoshioka & Kenji Fukuzawa

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  1. Akira Tokumura
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  2. Masaoki Toujima
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  3. Yasuko Yoshioka
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  4. Kenji Fukuzawa
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Tokumura, A., Toujima, M., Yoshioka, Y. et al. Lipid peroxidation in low density lipoproteins from human plasma and egg yolk promotes accumulation of 1-acyl analogues of platelet-activating factor-like lipids. Lipids 31, 1251–1258 (1996). https://doi.org/10.1007/BF02587909

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  • DOI: https://doi.org/10.1007/BF02587909

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