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.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Salgo MG,Squadrito GL,Pryor WAdoi
10.1021/tx00039a026subject
Has Abstractpub_date
1994-05-01 00:00:00pages
458-62issue
3eissn
0893-228Xissn
1520-5010journal_volume
7pub_type
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