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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.

Author information

1
Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Japan abeakira@sapmed.ac.jp.
2
Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
3
Life Sciences Institute and Departments of Pharmacology, Biological Chemistry, University of Michigan, Ann Arbor, MI.
4
Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, MI.

Abstract

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.

KEYWORDS:

catabolic pathway; lysosome; positional specificity; truncated oxidized phospholipid

PMID:
27993948
PMCID:
PMC5282950
DOI:
10.1194/jlr.M070730
[Indexed for MEDLINE]
Free PMC Article

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