Brown M S, Goldstein J L
Cell. 1975 Nov;6(3):307-16. doi: 10.1016/0092-8674(75)90182-8.
A specific receptor on the surface of cultured human fibroblasts 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, 25-hydroxycholesterol, or LDL progressively reduced the ability of the cells to bind 125I-labeled 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 125I-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 125I-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.
培养的人成纤维细胞表面的一种特异性受体能以高亲和力结合血浆低密度脂蛋白（LDL），从而启动一个细胞过程，在此过程中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LDL受体的活性受反馈调节。先用胆固醇、25-羟胆固醇或LDL孵育人成纤维细胞单层，会逐渐降低细胞在高亲和力位点结合125I标记LDL的能力。一系列动力学研究表明，这种结合能力的降低是由于LDL受体数量减少所致。根据环己酰亚胺给药后125I-LDL结合活性下降速率的测量结果，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125I-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受体活性又控制着培养基中源自血浆LDL的胆固醇进入细胞的速率。
