Abstract:
:PAF-dependent transacetylase (TA) modifies the functions of platelet-activating factor (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 activity). In stimulated endothelial cells (EC), TAL activity contributes to the synthesis of acyl-PAF, an acyl analog of PAF, that 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), that 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.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Balestrieri ML,Castaldo D,Balestrieri C,Quagliuolo L,Giovane A,Servillo Ldoi
10.1194/jlr.M200292-JLR200keywords:
subject
Has Abstractpub_date
2003-02-01 00:00:00pages
380-7issue
2eissn
0022-2275issn
1539-7262pii
M200292-JLR200journal_volume
44pub_type
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