Molecular and mechanistic characterization of platelet-activating factor-like bioactivity produced upon LDL oxidation

dc.contributor.authorAndroulakis, N.en
dc.contributor.authorDurand, H.en
dc.contributor.authorNinio, E.en
dc.contributor.authorTsoukatos, D. C.en
dc.date.accessioned2015-11-24T16:42:04Z
dc.date.available2015-11-24T16:42:04Z
dc.identifier.issn0022-2275-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/8508
dc.rightsDefault Licence-
dc.subjectoxidized phospholipidsen
dc.subjectplatelet-activating factor-acetylhydrolaseen
dc.subjectplatelet-activating factor-transacetylaseen
dc.subjectmediators of inflammationen
dc.subjectatherogenesisen
dc.subjectlow density lipoproteinen
dc.subjectlow-density-lipoproteinen
dc.subjectpaf-degrading acetylhydrolaseen
dc.subjecthuman-plasmaen
dc.subjectlipid-peroxidationen
dc.subjectfactor receptoren
dc.subjectatherosclerosisen
dc.subjectphosphatidylcholinesen
dc.subjectidentificationen
dc.subjectphospholipidsen
dc.subjectcholesterolen
dc.titleMolecular and mechanistic characterization of platelet-activating factor-like bioactivity produced upon LDL oxidationen
heal.abstractOxidation of LDL is thought to be involved in both initiating and sustaining atherogenesis through the formation of proinflammatory lipids and the covalent modification of LDL particles. Platelet- activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator involved in inflammation. Upon oxidation of LDL, oxidized phospholipids with PAF-like structure are generated, and some of them may act via the PAF receptor. We evaluated the contribution of 1-0-hexadecyl-2-acetylsn-glycero-3-phosphocholine (C16:0 PAF) and of other PAF analogs on the PAF-like bioactivity formed upon Cu2+- initiated oxidation of LDL. Reverse-phase HPLC purification and electrospray ionization-MS analyses showed that upon oxidation of LDL with inactivated PAF-acetylhydrolase (PAF-AH), C16:0 PAF accounted for > 30% of PAF-like biological activity and its sn-2 butenoyl analog accounted for > 50%. However, upon LDL oxidation in the presence of exogenous 1-0-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) without PAF-AH inactivation, C16:0 PAF formation accounted for > 90% of the biological activity recovered. We suggest that the C16:0 PAF, despite being a minor constituent of the LDL peroxidation products, may contribute substantially to the bioactivity formed in oxidized LDL. The higher bioactivity of C16:0 PAF, and the higher selectivity of the LDL-attached lyso-PAF transacetylase toward very short acyl chains [acetate (C2) vs. butanate (C4)], may explain the contribution described above.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primaryDOI 10.1194/jlr.M500074-JLR200-
heal.identifier.secondary<Go to ISI>://000231244200014-
heal.identifier.secondaryhttp://www.jlr.org/content/46/9/1923.full.pdf-
heal.journalNameJournal of Lipid Researchen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate2005-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείαςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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