Oxidized LDL activates phospholipase A2 to supply fatty acids required for cholesterol esterification

被引:32
作者
Akiba, S [1 ]
Yoneda, Y [1 ]
Ohno, S [1 ]
Nemoto, M [1 ]
Sato, T [1 ]
机构
[1] Kyoto Pharmaceut Univ, Dept Pathol Biochem, Yamashina Ku, Kyoto 6078414, Japan
关键词
cholesteryl ester; cytosolic phospholipase A(2); foam cell; hydroxyoctadecadienoic acid; macrophage;
D O I
10.1194/jlr.M300012-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We examined the roles of phospholipase A(2) (PLA(2)) in oxidized LDL (oxLDL)-induced cholesteryl ester formation in macrophages. In [H-3]oleic acid-labeled RAW264.7 cells and mouse peritoneal macrophages, oxLDL induced [H-3]cholesteryl oleate formation with an increase in free [H-3]oleic acid and a decrease in [H-3]phosphatidylcholine. The changes in these lipids were suppressed by methyl arachidonyl fluorophosphonate (MAFP), a cytosolic PLA(2) (cPLA(2)) inhibitor. However, MAFP had no effect on the ACAT activity or the binding and/or uptake of oxLDL. Stimulation with oxLDL in the presence of [H-3]cholesterol increased [H-3]cholesteryl ester bearing fatty acyl chains derived from cellular and/or exogenous (oxLDL) lipids. The formation of cholesteryl ester under this condition was also inhibited by MAFP, and the inhibitory effect was reversed by adding oleic acid. While oxLDL did not affect the activity or amounts of cPLA(2), preincubation with oxLDL enhanced the release of oleic acid and arachidonic acid induced by ionomycin in RAW264.7 cells. 13 (S)-hydroxyoctadecadienoic acid, but not 7-ketocholesterol, also enhanced ionomycin-induced oleic acid release. These results suggest that oxLDL induces cPLA(2) activation, which contributes, at least in part, to the supply of fatty acids required for the cholesteryl. esterification, probably through the acceleration by oxidized lipids of the catalytic action of cPLA(2) in macrophages.
引用
收藏
页码:1676 / 1685
页数:10
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