REGULATION OF ACTIVITY OF LOW-DENSITY LIPOPROTEIN RECEPTOR IN HUMAN FIBROBLASTS
REGULATION OF ACTIVITY OF LOW-DENSITY LIPOPROTEIN RECEPTOR IN HUMAN FIBROBLASTS
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DOI：
10.1016/0092-8674(75)90182-8
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发表时间：
1975-01-01
期刊：
影响因子：
64.5
通讯作者：
GOLDSTEIN, JL
中科院分区：
文献类型：
--
作者：
BROWN, MS;GOLDSTEIN, JL
培养的人成纤维细胞表面的一种特异性受体与血浆低密度脂蛋白（LDL）高亲和力结合，从而启动一个细胞过程，通过该过程，LDL被内化并在溶酶体内降解，其胆固醇成分可用于细胞膜合成。目前的研究表明，这种低密度脂蛋白受体的活性受到反馈调节。预先用胆固醇、25羟基胆固醇或低密度脂蛋白培养成纤维细胞单层，逐渐降低细胞在高亲和力位点结合' 2wlabeled LDL的能力。一系列动力学研究表明，这种结合的减少是由于LDL受体数量的减少。通过测量环己亚胺给药后' * 5l-LDL结合活性下降的速率，计算出LDL受体的半衰期约为25小时。LDL似乎通过抑制受体分子的合成来降低' * 51-LDL结合活性。因此，培养的人成纤维细胞通过调节LDL受体的活性来调节其细胞内胆固醇含量，而LDL受体反过来又控制来自培养基中血浆LDL的胆固醇进入细胞的速率。
A specific receptor on the surface of cultured human fibroflasts binds plasma low density lipoprotein (LDL) with high affinity, and thereby initiates a cellular process by which the LDL is internalized and degraded within lysosomes and its cholesterol component is made available for cellular membrane synthesis. Current studies demonstrate that the activity of this LDL receptor is under feedback regulation. Prior incubation of fibroblast monolayers with cholesterol, 25hydroxycholesterol, or LDL progressively reduced the ability of the cells to bind ‘2Wabeled LDL at the high affinity site. A series of kinetic studies indicated that this reduction in binding was due to a decrease in the number of LDL receptors. From measurements of the rate of decline in ‘* 5l-LDL binding activity after administration of cycloheximide, the LDL receptor was calculated to have a half-life of about 25 hr. LDL appeared to reduce ‘* 51-LDL-binding activity by suppressing the synthesis of receptor molecules. Thus cultured human fibroblasts regulate their intracellular cholesterol content by regulating the activity of the LDL receptor, which in turn controls the rate of cellular entry of cholesterol derived from plasma LDL contained within the culture medium.