Synthetic high density lipoprotein particles. Application to studies of the apoprotein specificity for selective uptake of cholesterol esters.

Synthetic high density lipoprotein particles. Application to studies of the apoprotein specificity for selective uptake of cholesterol esters.
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DOI:
10.1016/s0021-9258(18)61523-6
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发表时间:
1987-02
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
R. Pittman;C. Glass;D. Atkinson;D. Small
R. Pittman;C. Glass;D. Atkinson;D. Small
中科院分区:
其他
文献类型:
--
作者:
R. Pittman;C. Glass;D. Atkinson;D. Small

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用鸡蛋卵磷脂和油酸胆固醇制成的微乳液超声处理apoa - 1,制备了与大鼠高密度脂蛋白(HDL)在平衡密度分布和粒径上非常相似的颗粒。这些颗粒,像真正的高密度脂蛋白一样,允许培养细胞选择性地摄取它们的胆固醇酯部分,而不平行摄取颗粒本身。这种摄取是饱和的,并与HDL竞争。大鼠的血浆衰变动力学和摄取胆固醇醚示踪剂的部位是相似的,无论该示踪剂是否被纳入合成或真实的HDL。含有其他载脂蛋白的合成颗粒是用一般相同的方法制成的,但用大鼠载脂蛋白或载脂蛋白E的混合物代替apoA-I,这些载脂蛋白或载脂蛋白E要么是有效的,要么是还原甲基化的,以防止与B/E受体相互作用。与apoa - 1形成的颗粒相比,这些颗粒密度更低,斯托克斯半径更大,也允许选择性摄取胆固醇酯,尽管其选择性程度低于apoa - 1。因此,受试者脂蛋白颗粒中的特定载脂蛋白成分不需要选择性摄取。然而,选择性摄取被证明是粒子密度或大小的函数,不同载脂蛋白组成的粒子的选择性摄取率的部分差异可以用它们的密度或大小的差异来解释。
Particles closely resembling rat high density lipoproteins (HDL) in terms of equilibrium density profile and particle size were prepared by sonication of apoA-I with a microemulsion made with egg lecithin and cholesterol oleate. These particles, like authentic HDL, allowed selective uptake of their cholesterol ester moieties by cultured cells without parallel uptake of the particle itself. That uptake was saturable and competed by HDL. In rats, the plasma decay kinetics and sites of uptake of a cholesteryl ether tracer were similar whether that tracer was incorporated into synthetic or authentic HDL. Synthetic particles containing other apoproteins were made by generally the same method, but using in place of apoA-I either a mixture of rat apoCs or apoE that was either competent or reductively methylated to prevent interaction with the B/E receptor. These particles, of lower density and larger Stokes radius than those made with apoA-I, also allowed selective uptake of cholesterol esters, albeit with a lower degree of selectivity than in the case of apoA-I. Thus a specific apoprotein component in the subject lipoprotein particle is not required for selective uptake. However, selective uptake was shown to be a function of particle density or size, and part of the difference in rates of selective uptake from the particles made with various apoproteins was explained by their differences in density or size.