title: Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein.
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.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sasabe
authors.forename: Yuka
authors.initials: Y
authors.lastname: Keyamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Obama
authors.forename: Nozomi
authors.initials: N
authors.lastname: Inoue
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Masuko
authors.forename: Yu
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Aiuchi
authors.forename: Rina
authors.initials: R
authors.lastname: Kato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuwata
authors.forename: Sanju
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo, Japan. h-itabe@pharm.showa-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors / Q000737:chemistry; D000818:Animals; D001055:Apolipoproteins B / Q000737:chemistry; D019327:Copper Sulfate / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D016877:Oxidants; D010713:Phosphatidylcholines; D015842:Serine Proteinase Inhibitors; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D019327:Copper Sulfate