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Papers In Press, published online ahead of print November 4, 2002 J. Lipid Res., doi:10.1194/jlr.M200292-JLR200
Submitted on July 24, 2002
Dept. Biochemistry and Biophysics, Second University of Naples, Napoli 80138
Corresponding Author: luigi.servillo{at}unina2.it
PAF-dependent Transacetylase (TA) modifies the functions of PAF, a potent inflammatory lipid, either by transferring the acetyl group from PAF to lysophospholipids (TAL activity), or to sphingosine (TAS activity) or by hydrolyzing PAF (acetylhydrolase, AH activity). In stimulated endothelial cells (EC), TAL activity contributes to the synthesis of acyl-PAF, an acyl analog of PAF which antagonizes PAF functions, and is regulated by the cellular redox state. In this study we investigated the possible involvement of TA in the flavonoid antioxidant mechanism(s) during oxidative stress in EC induced by hydrogen peroxide. The treatment of EC with H2O2 resulted in 4-fold increase of the acetyl-CoA acetyltransferase activity (AT), which is responsible for PAF biosynthesis, while the TAL activity increased only by 53 %. However, the preincubation of H2O2-treated EC with the flavonoids hesperedin, naringin and quercetin strongly inhibited AT activity and activated TAL by 290%, 340% and 250%, respectively. The induction of TAL activity resulted in enhanced biosynthesis of 1-acyl-2-[3H]acetyl-PAF in intact EC and was related to the flavonoid structure. These findings suggest that TAL is involved in the flavonoid anti-inflammatory action by enhancing the production of acyl-PAF.
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