title: Platelet Activating Factor (PAF) biosynthesis is inhibited by phenolic compounds in U-937 cells under inflammatory conditions.
abstract: Interleukin 1 beta (IL-1β) induced platelet activating factor (PAF) synthesis in U-937 cells through stimulation of acetyl-CoA:lysoPAF-acetyltransferase (lyso PAF-AT) at 3 h and DTT-independentCDP-choline-1-alkyl-2-acetyl-sn-glycerol cholinophosphotransferase (PAF-CPT) at 0.5 h. The aim of this study was to investigate the effect of tyrosol (T), resveratrol (R) and their acetylated derivatives(AcDs) which exhibit enhanced bioavailability, on PAF synthesis in U-937 after IL-1β stimulation. The specific activity of PAF enzymes and intracellular levels were measured in cell homogenates. T and R concentration capable of inducing 50% inhibition in IL-1β effect on lyso PAF-AT was 48 μΜ ± 11 and 157 μΜ ± 77, for PAF-CPT 246 μΜ ± 61 and 294 μΜ ± 102, respectively. The same order of concentration was also observed on inhibiting PAF levels produced by IL-1β. T was more potent inhibitor than R (p<0.05). AcDs of T retain parent compound inhibitory activity, while in the case of R only two AcDs retain the activity. The observed inhibitory effect by T,R and their AcDs, may partly explain their already reported beneficial role.
authors.affiliation: Department of Nutritional Science and Dietetics, Harokopio University, Athens, Greece.
authors.forename: Ioanna C
authors.initials: IC
authors.lastname: Vlachogianni
authors.affiliation: Department of Nutritional Science and Dietetics, Harokopio University, Athens, Greece.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fragopoulou
authors.affiliation: Faculty of Chemistry, National and Kapodistrian University, Athens, Greece.
authors.forename: George M
authors.initials: GM
authors.lastname: Stamatakis
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece.
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Kostakis
authors.affiliation: Department of Nutritional Science and Dietetics, Harokopio University, Athens, Greece. Electronic address: antonop@hua.gr.
authors.forename: Smaragdi
authors.initials: S
authors.lastname: Antonopoulou
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002798:Diacylglycerol Cholinephosphotransferase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009994:Osmolar Concentration; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004791:Enzyme Inhibitors; C508585:IL1B protein, human; D053583:Interleukin-1beta; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D013267:Stilbenes; C011867:4-hydroxyphenylethanol; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D010626:Phenylethyl Alcohol; D000077185:Resveratrol
keywords: Acetylation; IL-1β; Lyso PAF-acetyltransferase; PAF; Tyrosol; resveratrol