Lipid peroxidation in low density lipoproteins from human plasma and egg yolk promotes accumulation of 1-acyl analogues of platelet-activating factor-like lipids.
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 an sn-2-short-chain dicarboxylate or monocarboxylate group. Only a very small amount of the PAF-like lipid having an sn-2-short-chain monocarboxylate group was detected by gas chromatography-mass spectrometry in Cu(2+)-oxidized LDL from human plasma with high PAF-acetylhydrolase activity, which has been reported to hydrolyze PAF-like lipids to lysophosphatidyl-cholines. 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.
Tokumura
A
A
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Toujima
M
M
Yoshioka
Y
Y
Fukuzawa
K
K
D000215:Acylation; D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D004530:Egg Yolk / Q000737:chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry / Q000633:toxicity; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013936:Thymidine / Q000378:metabolism
D008055:Lipids; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D013936:Thymidine