title: Enhancement of acetyl-CoA: 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity by hydrogen peroxide.
abstract: The synthesis of platelet-activating factor (PAF) by human umbilical vein endothelial cell (HUVEC) in response to H2O2 was significantly increased in a concentration-dependent manner. When HUVEC were pretreated with diethyl maleate, which depletes intracellular glutathione, PAF synthesis was enhanced 3-fold upon 5 mM H2O2-treatment. Intracellular redox was involved in regulating PAF synthesis, since the addition of antioxidants such as N-acetylcysteine, pyrrolidinecarbodithioic acid (PDTC), and Trolox reduced PAF production in H2O2-treated HUVEC. The activity of acetyl-CoA: 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase, which is involved in the last step of PAF synthesis, was also activated in H2O2-treated cells. However, exogenous lyso-PAF addition had not effected to acetyltransferase activity. The acetyltransferase activity responded quickly to H2O2-treatment, but the activation was transitory. A tyrosine kinase inhibitor and a calmodulin antagonist blocked acetyltransferase activity in H2O2-stimulated cells, suggesting that tyrosine kinase and calcium/calmodulin-dependent protein kinase are involved in regulating acetyltransferase activity. These observations suggest that H2O2 is one of the modulators of lyso-PAF acetyltransferase activity via a phosphorylation system and platelet-activating factor (PAF) synthesis.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Tosaki
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Kitahara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Imai
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nakagawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000123:Acetyltransferases / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D005978:Glutathione / Q000172:deficiency; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008298:Maleates / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000096:biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D000096926:Benzenesulfonamides
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000123:Acetyltransferases; D000975:Antioxidants; D016718:Arachidonic Acid; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002147:Calmodulin; D019833:Genistein; D005978:Glutathione; D006861:Hydrogen Peroxide; D008298:Maleates; D016877:Oxidants; D010972:Platelet Activating Factor; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C017967:W 7; C027628:acetyl-CoA-1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase; C014476:diethyl maleate