Inhibition of endothelial lipase activity by sphingomyelin in the lipoproteins.
Inhibition of endothelial lipase activity by sphingomyelin in the lipoproteins.
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DOI：
10.1007/s11745-014-3944-1
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发表时间：
2014-10
期刊：
影响因子：
1.9
通讯作者：
Subbaiah PV
中科院分区：
文献类型：
--
作者：
Yang P;Belikova NA;Billheimer J;Rader DJ;Hill JS;Subbaiah PV
内皮脂酶（EL）是血浆HDL浓度的主要决定因素，其活性与HDL水平成反比。虽然已知与LDL和VLDL相比，它优先作用于HDL，但这种特异性的基础尚不清楚。在这里，我们测试的假设，鞘磷脂，脂蛋白中的主要磷脂是EL的生理抑制剂，和HDL的酶的偏好可能是由于低鞘磷脂/磷脂酰胆碱（PtdCho）的比例在HDL中，相比于其他脂蛋白。使用重组人EL，我们表明，鞘磷脂抑制PtdCho在脂质体中的水解以浓度依赖性的方式。虽然该酶表现出较低的水解LDL PtdCho，相比HDL PtdCho，这种差异消失后，细菌鞘磷脂酶的脂蛋白鞘磷脂降解。对脂蛋白中PtdCho的分子种类分析表明，该酶优先水解sn-2位含有22：6、20：5、20：4等多不饱和脂肪酸（PUFA）的PtdCho，生成相应的PUFA-lyso PtdCho。在鞘磷脂酶耗尽鞘磷脂后，未观察到PUFA-PtdCho物质的这种特异性。这些结果表明，鞘磷脂不仅在调节EL活性中起作用，而且影响其对PtdCho种类的特异性。
Endothelial lipase (EL) is a major determinant of plasma HDL concentration, its activity being inversely proportional to HDL levels. Although it is known that it preferentially acts on HDL, compared to LDL and VLDL, the basis for this specificity is not known. Here we tested the hypothesis that sphingomyelin, a major phospholipid in lipoproteins is a physiological inhibitor of EL, and that the preference of the enzyme for HDL may be due to low sphingomyelin/ phosphatidylcholine (PtdCho) ratio in HDL, compared to other lipoproteins. Using recombinant human EL, we showed that sphingomyelin inhibits the hydrolysis of PtdCho in the liposomes in a concentration-dependent manner. While the enzyme showed lower hydrolysis of LDL PtdCho, compared to HDL PtdCho, this difference disappeared after the degradation of lipoprotein sphingomyelin by bacterial sphingomyelinase. Analysis of molecular species of PtdCho hydrolyzed by EL in the lipoproteins showed that the enzyme preferentially hydrolyzed PtdCho containing polyunsaturated fatty acids (PUFA) such as 22:6, 20:5, 20:4 at sn-2 position, generating the corresponding PUFA-lyso PtdCho. This specificity for PUFA-PtdCho species was not observed after depletion of sphingomyelin by sphingomyelinase. These results show that sphingomyelin not only plays a role in regulating EL activity, but also influences its specificity towards PtdCho species.