Oxidized LDL activates phospholipase A2 to supply fatty acids required for cholesterol esterification
Oxidized LDL activates phospholipase A2 to supply fatty acids required for cholesterol esterification
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DOI：
10.1194/jlr.m300012-jlr200
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发表时间：
2003-09-01
影响因子：
6.5
通讯作者：
Sato, T
中科院分区：
文献类型：
--
作者：
Akiba, S;Yoneda, Y;Sato, T
我们研究了磷脂酶A（2）（PLA（2））在氧化低密度脂蛋白（oxLDL）诱导的巨噬细胞胆固醇酯形成中的作用。在[H-3]油酸标记的RAW 264.7细胞和小鼠腹腔巨噬细胞中，oxLDL诱导[H-3]胆固醇油酸酯形成，游离[H-3]油酸增加，[H-3]磷脂酰胆碱减少。这些脂质的变化被胞质PLA（2）（cPLA（2））抑制剂甲基花生四烯酰氟膦酸酯（MAFP）抑制。然而，MAFP对ACAT活性或oxLDL的结合和/或摄取没有影响。刺激oxLDL的存在下，[H-3]胆固醇增加[H-3]胆固醇酯轴承脂肪酰基链来自细胞和/或外源性（oxLDL）脂质。在此条件下，胆固醇酯的形成也被MAFP抑制，并通过添加油酸逆转抑制效果。虽然oxLDL不影响cPLA（2）的活性或数量，但与oxLDL预孵育可增强RAW 264.7细胞中由离子霉素诱导的油酸和花生四烯酸的释放。13（S）-羟基十八碳二烯酸，而不是7-酮胆固醇，也增强离子霉素诱导的油酸释放。这些结果表明，oxLDL诱导cPLA（2）活化，这至少部分有助于胆固醇所需的脂肪酸的供应。酯化，可能是通过氧化脂质加速cPLA（2）在巨噬细胞中的催化作用。
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.