Esterification of side-chain oxysterols by lysosomal phospholipase A2
| Autor: | Seiichi Aikawa, Fumiko Matsuzawa, Miki Hiraoka, Youichi Niimura, Akira Abe |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oxysterol Sterol O-acyltransferase 01 natural sciences Catalysis Phosphatidylcholine-Sterol O-Acyltransferase 03 medical and health sciences chemistry.chemical_compound Mice Transacylation Sphingosine Amphiphile polycyclic compounds Animals Humans Lipid bilayer Molecular Biology Liposome Esterification 010405 organic chemistry Cholesterol Macrophages Cell Biology Oxysterols Hydroxycholesterols 0104 chemical sciences Phospholipases A2 030104 developmental biology Biochemistry chemistry Acyltransferase lipids (amino acids peptides and proteins) Lysosomes |
| Zdroj: | Biochimica et biophysica acta. Molecular and cell biology of lipids. 1865(10) |
| ISSN: | 1879-2618 |
| Popis: | Side-chain oxysterols produced from cholesterol either enzymatically or non-enzymatically show various bioactivities. Lecithin-cholesterol acyltransferase (LCAT) esterifies the C3-hydroxyl group of these sterols as well as cholesterol. Lysosomal phospholipase A2 (LPLA2) is related to LCAT but does not catalyze esterification of cholesterol. First, esterification of side-chain oxysterols by LPLA2 was investigated using recombinant mouse LPLA2 and dioleoyl-PC/sulfatide/oxysterol liposomes under acidic conditions. TLC and LC-MS/MS showed that the C3 and C27-hydroxyl groups of 27-hydroxycholesterol could be individually esterified by LPLA2 to form a monoester with the C27-hydroxyl preference. Cholesterol did not inhibit this reaction. Also, LPLA2 esterified other side-chain oxysterols. Their esterifications by mouse serum containing LCAT supported the idea that their esterifications by LPLA2 occur at the C3-hydroxyl group. N-acetylsphingosine (NAS) acting as an acyl acceptor in LPLA2 transacylation inhibited the side-chain oxysterol esterification by LPLA2. This suggests a competition between hydroxycholesterol and NAS on the acyl-LPLA2 intermediate formed during the reaction. Raising cationic amphiphilic drug concentration or ionic strength in the reaction mixture evoked a reduction of the side-chain oxysterol esterification by LPLA2. This indicates that the esterification could progress via an interfacial interaction of LPLA2 with the lipid membrane surface through an electrostatic interaction. The docking model of acyl-LPLA2 intermediate and side-chain oxysterol provided new insight to elucidate the transacylation mechanism of sterols by LPLA2. Finally, exogenous 25-hydroxycholesterol esterification within alveolar macrophages prepared from wild-type mice was significantly higher than that from LPLA2 deficient mice. This suggests that there is an esterification pathway of side-chain oxysterols via LPLA2. |
| Databáze: | OpenAIRE |
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