title: Apolipoprotein A-I promotes the formation of phosphatidylcholine core aldehydes that are hydrolyzed by paraoxonase (PON-1) during high density lipoprotein oxidation with a peroxynitrite donor.
abstract: High density lipoprotein (HDL) is rich in polyunsaturated phospholipids that are sensitive to oxidation. However, the effect of apolipoprotein A-I and paraoxonase-1 (PON-1) on phosphatidylcholine oxidation products has not been identified. We subjected native HDL, trypsinized HDL, and HDL lipid suspensions to oxidation by the peroxynitrite donor, 3-morpholinosydnonimine. HDL had a basal level of phosphatidylcholine mono- and di-hydroperoxides that increased to a greater extent in HDL, compared with either trypsinized HDL or HDL lipid alone. Phosphatidylcholine core aldehydes, which were present in small amounts, increased 10-fold during oxidation of native HDL, compared with trypsinized HDL (p = 0.004), and 4-fold compared with HDL lipid suspensions (p = 0.0021). In addition, the content of lysophosphatidylcholine increased 300% during oxidation of native HDL, but only 80 and 25%, respectively, during oxidation of trypsinized HDL and HDL lipid suspensions. Phosphatidylcholine isoprostanes accumulated in comparable amounts during the oxidation of all three preparations. Incubation of apolipoprotein A-I with 1-palmitoyl-2-linoleoyl glycerophosphocholine proteoliposomes in the presence of 3-morpholinosydnonimine or apoAI with phosphatidylcholine hydroperoxides resulted in a significant increase in phosphatidylcholine core aldehydes with no formation of lysophosphatidylcholine. We propose that apolipoprotein A-I catalyzes a one-electron oxidation of alkoxyl radicals. Purified PON-1 hydrolyzed phosphatidylcholine core aldehydes to lysophosphatidylcholine. We conclude that, upon HDL oxidation with peroxynitrite, apolipoprotein AI increases the formation of phosphatidylcholine core aldehydes that are subsequently hydrolyzed by PON1.
authors.affiliation: J. Alick Little Lipid Research Laboratory, St. Michael's Hospital, University of Toronto, 38 Shuter Street, Toronto, Ontario M5B 1A6, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Ahmed
authors.forename: A
authors.initials: A
authors.lastname: Ravandi
authors.forename: G F
authors.initials: GF
authors.lastname: Maguire
authors.forename: A
authors.initials: A
authors.lastname: Emili
authors.forename: D
authors.initials: D
authors.lastname: Draganov
authors.forename: B N
authors.initials: BN
authors.lastname: La Du
authors.forename: A
authors.initials: A
authors.lastname: Kuksis
authors.forename: P W
authors.initials: PW
authors.lastname: Connelly
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D043303:Aryldialkylphosphatase; D004591:Electrophoresis, Polyacrylamide Gel; D004950:Esterases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
chemical_list: D000447:Aldehydes; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008244:Lysophosphatidylcholines; D009566:Nitrates; D010713:Phosphatidylcholines; D011510:Proteolipids; C020485:proteoliposomes; C039642:peroxynitric acid; C002385:linsidomine; D008981:Molsidomine; D004950:Esterases; D010741:Phospholipases A; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D014357:Trypsin