Modulation by flavonoids of PAF and related phospholipids in endothelial cells during oxidative stress

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 (TA(L) activity), or to sphingosine (TA(S) activity) or by hydrolyzing PAF (acetylhydrolase activity). In stimulated endothelial cells (EC), TA(L) 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 TA(L) 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 TA(L) by 290%, 340%, and 250%, respectively. The induction of TA(L) activity resulted in enhanced biosynthesis of 1-acyl-2-[H-3]acetyl-PAF in intact EC and was related to the flavonoid structure. These findings suggest that TA(L) is involved in the flavonoid anti-inflammatory action by enhancing the production of acyl-PAF.