Enhancement of acetyl-CoA: 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity by hydrogen peroxide

Biol Pharm Bull. 2007 Feb;30(2):272-8. doi: 10.1248/bpb.30.272.

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.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Acetyltransferases / metabolism*
  • Antioxidants / pharmacology
  • Arachidonic Acid / metabolism
  • Benzylamines / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Calmodulin / antagonists & inhibitors
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Genistein / pharmacology
  • Glutathione / deficiency
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Maleates / pharmacology
  • Oxidants / pharmacology*
  • Platelet Activating Factor / biosynthesis
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Sulfonamides / pharmacology
  • Umbilical Veins / cytology

Substances

  • Antioxidants
  • Benzylamines
  • Calmodulin
  • Maleates
  • Oxidants
  • Platelet Activating Factor
  • Protein Kinase Inhibitors
  • Sulfonamides
  • KN 93
  • Arachidonic Acid
  • W 7
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Hydrogen Peroxide
  • Genistein
  • Acetyltransferases
  • acetyl-CoA-1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • diethyl maleate
  • Glutathione