Phospholipase A(2) activity in non-glycated and glycated low density lipoproteins

The oxidation of low density lipoprotein (LDL) is believed to be an important risk factor for atherosclerosis. We have previously reported that glycation of LDL enhances LDL oxidation. Incubation of LDL in the presence of 200 mM glucose resulted in the enhanced formation of phosphatidylcholine hydroperoxide (PC-OOH) and cholesteryl ester hydroperoxide (CE-OOH). Fe(3+)-ADP accelerated the formation of hydroperoxides. The concentration of PC-OOH was much smaller than that of CE-OOH. In addition, we found a PC-OOH decomposing activity in LDL by following linoleic acid hydroperoxide (18:2-OOH) formation from 1-stearoyl-2-[13'-(S)-hydroperoxy-9', 11'-octadecadienoyl]-sn-glycero-3-phosphocholine (SLPC-OOH). Hydrolysis was similar between LDL and glycated LDL. Pretreatment by para-bromophenacylbromide, histidine modifier and phospholipase A(2) inhibitor, retarded the formation of 18:2-OOH only by 30%. The addition of equimolar platelet activating factor (PAF) reduced hydrolysis by 50%, indicating PAF acetylhydrolase may be responsible for the hydrolysis of PC-OOH.