Non‐enzymatic platelet‐activating factor formation by acetylated proteins

Abstract

Substantial amounts of platelet-activating factor (PAF 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine), the potent phospholipid mediator of allergic and inflammatory reactions, are formed upon incubation of acetylated low-density lipoprotein, acetylated bovine serum albumin (BSA) and acetylated apolipoprotein A-I with 1-0-hexadecyl-sn-glycero-3-phosphocholine (lyso-PAF). Acetylated BSA produced 0.3 nmol PAF/mg of protein after a 6 h incubation period with 40 lM lyso-PAF. The transfer of acetate bound to acetylated proteins to lyso-PAF was non-enzymatic. Chemical PAF formation by acetylated proteins, involved in lipid metabolism and transport, could lead to complication of inflammatory and allergic events.

Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT

“…COX2, an isoform of COX1, is reported to get acetylated in its active site Ser-516 in the same way as it binds to Ser-530 of COX1 [45]. Some reports claim that aspirin is capable of acetylating diverse cellular proteins such as human serum albumin [46], fibrinogen [47], hemoglobin [48], endothelial NOS [49], and tumor suppressor protein p53 [50] at the N ε -lysine residues, to regulate their functions [9]. Some workers have reported the formation of platelet activating factor (PAF) from a nonspecific and nonenzymatic transfer of acetate from acetylated bovine serum albumin and apolipoproteins (acetylated by acetic anhydride) to lyso-PAF [50].…”