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J Lipid Res. 2017 Feb;58(2):339-349. doi: 10.1194/jlr.M070730. Epub 2016 Dec 19.

Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2.

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Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Japan
Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Life Sciences Institute and Departments of Pharmacology, Biological Chemistry, University of Michigan, Ann Arbor, MI.
Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, MI.


Truncated oxidized glycerophospholipids (ox-PLs) are bioactive lipids resulting from oxidative stress. The catabolic pathways for truncated ox-PLs are not fully understood. Lysosomal phospholipase A2 (LPLA2) with phospholipase A and transacylase activities is a key enzyme in phospholipid homeostasis. The present study assessed whether LPLA2 could hydrolyze truncated ox-PLs. Incubation of LPLA2 with liposomes consisting of 1,2-O-octadecenyl-sn-glycero-3-phosphocholine (DODPC)/1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or truncated oxidized phosphatidylcholine (ox-PC)/N-acetylsphingosine (NAS) under acidic conditions resulted in the preferential deacylation at the sn-1 position of the truncated ox-PCs. Additionally, the release of free fatty acid from the truncated ox-PCs preferentially occurred compared with the NAS-acylation. Incubation of LPLA2 with the liposomes consisting of DODPC/DOPC/truncated ox-PC/NAS resulted in the same preferential fatty acid release from the truncated ox-PC. The cationic amphiphilic drug, amiodarone, did not inhibit such fatty acid release, indicating that truncated ox-PCs partition from the lipid membrane into the aqueous phase and react with free LPLA2. Consistent with this mechanism, the hydrolysis of some truncated ox-PCs, but not DOPC, by LPLA2 was detected at neutral pH. Additionally, LPLA2-overexpressed Chinese hamster ovary cells efficiently catabolized truncated ox-PC and were protected from growth inhibition. These findings support the existence of a novel catabolic pathway for truncated ox-PLs via LPLA2.


catabolic pathway; lysosome; positional specificity; truncated oxidized phospholipid

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