Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins.
Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins.
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DOI：
10.3390/antiox9111045
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发表时间：
2020-10-26
期刊：
影响因子：
--
通讯作者：
Itabe H
中科院分区：
文献类型：
--
作者：
Sawada N;Obama T;Mizuno M;Fukuhara K;Iwamoto S;Aiuchi T;Makiyama T;Itabe H
氧化低密度脂蛋白（oxLDL）和氧化高密度脂蛋白（oxHDL），被称为心血管疾病的危险因素，已被观察到在血浆和动脉粥样硬化斑块。在先前的研究中，氧化磷脂酰胆碱（oxPC）和溶血磷脂酰胆碱（lysoPC）的含量在体内oxLDL中保持恒定，但在体外铜诱导的oxLDL中增加。在这项研究中，我们制备了合成的氘标记的1-棕榈酰lysoPC和棕榈酰戊二酰PC（PGPC），一个短链oxPC，以阐明oxPC和lysoPC在HDL存在下的oxLDL的代谢命运。当与d13-lysoPC预载的LDL与HDL混合时，d13-lysoPC在LDL和HDL级分中相等地回收。孵育4小时后，d13-LysoPC减少50%，而d13-PC在两种组分中均增加。卵磷脂胆固醇酰基转移酶（LCAT）的抑制剂，废除二酰基-PC的生产。当d13-PGPC-预载LDL与HDL孵育时，当LCAT和脂蛋白相关磷脂酶A2（Lp-PLA 2）均被抑制时，d13-PGPC以剂量依赖性方式转移至HDL。HDL和LDL中的Lp-PLA 2参与d13-PGPC的水解。这些结果表明，短链oxPC和lysoPC可以迅速转移脂蛋白之间，可以酶促oxPC转化为lysoPC和lysoPC的存在下，HDL的二酰基PC。
Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL), known as risk factors for cardiovascular disease, have been observed in plasma and atheromatous plaques. In a previous study, the content of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) species stayed constant in isolated in vivo oxLDL but increased in copper-induced oxLDL in vitro. In this study, we prepared synthetic deuterium-labeled 1-palmitoyl lysoPC and palmitoyl-glutaroyl PC (PGPC), a short chain-oxPC to elucidate the metabolic fate of oxPC and lysoPC in oxLDL in the presence of HDL. When LDL preloaded with d13-lysoPC was mixed with HDL, d13-lysoPC was recovered in both the LDL and HDL fractions equally. d13-LysoPC decreased by 50% after 4 h of incubation, while d13-PC increased in both fractions. Diacyl-PC production was abolished by an inhibitor of lecithin-cholesterol acyltransferase (LCAT). When d13-PGPC-preloaded LDL was incubated with HDL, d13-PGPC was transferred to HDL in a dose-dependent manner when both LCAT and lipoprotein-associated phospholipase A2 (Lp-PLA2) were inhibited. Lp-PLA2 in both HDL and LDL was responsible for the hydrolysis of d13-PGPC. These results suggest that short chain-oxPC and lysoPC can transfer between lipoproteins quickly and can be enzymatically converted from oxPC to lysoPC and from lysoPC to diacyl-PC in the presence of HDL.
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影响因子：
15.9
作者：
ROSENFELD, ME;KHOO, JC;WITZTUM, JL
通讯作者：
WITZTUM, JL
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7.4
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Hoff, HF
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4.5
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通讯作者：
Itabe H