1. Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein.
- Author
-
Naoko Sasabe, Yuka Keyamura, Takashi Obama, Nozomi Inoue, Yukihiro Masuko, Yu Igarashi, Toshihiro Aiuchi, Rina Kato, Tomohiro Yamaguchi, Hiroshi Kuwata, Sanju Iwamoto, Akira Miyazaki, Shuntaro Hara, Tomohiro Yoshikawa, and Hiroyuki Itabe
- Subjects
LOW density lipoproteins ,LECITHIN ,LIQUID chromatography-mass spectrometry ,BLOOD lipoproteins ,PHOSPHOLIPIDS - Abstract
Background: Oxidized phosphatidylcholines (oxPC) and lysophosphatidylcholine (lysoPC) generated during the formation of oxidized low-density lipoprotein (oxLDL) are involved in atherosclerotic lesion development. We investigated the time course-changes in phosphatidylcholine (PC) molecular species during oxidation of LDL to determine how those atherogenic PCs are produced. Methods: Human and rabbit LDLs were pretreated with or without a selective platelet-activating factor acetylhydrolase (PAF-AH) inhibitor. LDL was oxidized by incubation with copper sulfate, and PC profiles were analyzed by liquid chromatography-tandem mass spectrometry. Results: When human LDL was oxidized, the peak areas for polyunsaturated fatty acid (PUFA)-containing PC species dramatically decreased after a short lag period, concomitantly lysoPC species increased sharply. Although a variety of oxPC species containing oxidized fatty acyl groups or cleaved acyl chains are formed during LDL oxidation, only a few oxPC products accumulated in oxLDL: 1-palmitoyl-2-(9-oxo-nonanoyl) PC and long-chain oxPC with two double bonds. Pretreatment of LDL with the PAF-AH inhibitor greatly reduced lysoPC production while it had no effect on lipid peroxidation reactions and oxPC profiles. Rabbit LDL, which has a different composition of PC molecular species and needs a longer time to reach achieve full oxidation than human LDL, also accumulated lysoPC during oxidation. The increase in lysoPC in rabbit oxLDL was suppressed by pretreatment with the PAF-AH inhibitor. The major oxPC species formed in rabbit oxLDL were almost the same as human oxLDL. Conclusions: These results suggest that lysoPC species are the major products and PAF-AH activity is crucial for lysoPC generation during oxidation of LDL. The oxPC species accumulated are limited when LDL is oxidized with copper ion in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF