The Role of Platelet-activating Factor-dependent Transacetylase in the Biosynthesis of 1-Acyl-2-acetyl-sn-glycero-3-phosphocholine by Stimulated Endothelial Cells

Abstract

Acyl analogs of platelet-activating factor (PAF) (1-acyl-2-acetyl-sn-glycero-3-phosphocholine, acylacetyl -GPC) are the predominant products synthesized during thrombin or ionophore A23187-mediated activation of endothelial cells. However, the biosynthetic pathway responsible for the production of acylacetyl-GPC is not well understood. In the present investigation, we have demonstrated that the acyl analogs of PAF are also the major products from calf pulmonary artery endothelial cells in response to a time-dependent stimulation of ATP (10 ؊3 M), bradykinin (10 ؊8 M), or ionophore A23187 (2 M).

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

“…2B). Since the TA L strongly contributes to the acyl-PAF biosynthesis in activated EC (9), these data indicated that during induced oxidative stress, the activation of AT is predominant and that TA L scarcely contributes to the acyl-PAF biosynthesis.…”

“…The LDL susceptibiliy to oxidative modifications can be decreased by acyl-PAF, (8) an acyl analog of PAF (1). Acyl-PAF is the predominant component produced by activated EC, and the TA L contributes to its biosynthesis (9,10). The inhibition of LDL oxidation is a well-characterized process that includes effects on the concentration or reactivity of oxidants capable of modifying LDL and on the susceptibility or resistance of LDL to these oxidants.…”

“…TA L , TA s , and AH activities were determined according to the methods we previously described (9,3 …”

“…Homogenates were prepared in the homogenization buffer (0.25 M sucrose, 100 mM Tris-HCl, pH 7.3, 1 g/ml leupeptin, 1 mM dithiotreitol) by sonication, and the protein content of the cell homogenates was determined as previously described (9).…”

“…Moreover, acyl-PAF decreases the susceptibility of the LDL particle to oxidative modifications (8). In activated ECs, TA L contributes to the biosynthesis of acyl-PAF (9,10), and its activity is regulated by the thiol cellular levels [i.e., glutathione (GSH)] (11). In particular, the enzyme activity increases in the presence of thiol-oxidant agents and is decreased by thiol-antioxidants (11).…”