title: Activation of phospholipase A2 in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes containing lipid ozonation products.
abstract: The activation of phospholipase A2 (PLA2) by lipid ozonation products is reported. The principal products from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) are 1-palmitoyl-2-[8-[3(5-octyl-1,2,4-trioxolan-3-yl)octanoyl]--sn-gly cero-3- phosphocholine (PC-Criegee ozonide) and 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3- phosphocholine (PC-aldehyde). (See Figure 1 for structures.) Here we test the hypothesis that these two compounds are mediators of ozone toxicity. Using POC vesicles, we find that PLA2 recognizes and hydrolyzes PC-Criegee ozonide at the same rate as that of arachidonic acid. Although the PC-aldehyde is not a substrate for PLA2, the enzymatic rate of hydrolysis by PLA2 of unaltered fatty acids incorporated into POPC is enhanced when PC-aldehyde is present in the bilayer. Thus, both PC-Criegee ozonide and PC-aldehyde alter the activity of PLA2, perhaps via an effect on membrane packing order. The capacity of PLA2 to recognize the PC-Criegee, and therefore ozone-induced damage, suggests a detoxification property of the enzyme and also a role in maintaining the structural properties of bilayer membranes that have been altered by exposure to ozone.
authors.affiliation: Biodynamics Institute, Louisiana State University, Baton Rouge 70803.
authors.forename: M G
authors.initials: MG
authors.lastname: Salgo
authors.forename: G L
authors.initials: GL
authors.lastname: Squadrito
authors.forename: W A
authors.initials: WA
authors.lastname: Pryor
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D010126:Ozone / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013379:Substrate Specificity
chemical_list: D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010126:Ozone; D010741:Phospholipases A; D054467:Phospholipases A2; C028694:1-palmitoyl-2-oleoylphosphatidylcholine