Fung C H, Khachadurian A K
J Biol Chem. 1980 Jan 25;255(2):676-80.
In cultured skin fibroblasts from normal and homozygous familial hypercholesterolemic subjects, a water-soluble polyoxyethylated derivative of cholesterol suppresses the incorporation of [2-14C]acetate into cholesterol and decreases the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis. The effect of this compound on low density lipoprotein (LDL) receptor-mediated activities (binding, internalization, and degradation of LDL) and on cholesterol ester formation was compared to that of LDL and 25-hydroxycholesterol. In normal fibroblasts preincubated in lipoprotein-deficient serum, LDL or 25-hydroxycholesterol decreased cholesterol synthesis and LDL receptor activity and increased cholesterol ester formation. In contrast, polyoxyethylated cholesterol stimulated LDL receptor activity, inhibited cholesterol ester formation mediated by LDL and 25-hydroxycholesterol, and inhibited the activity of acyl-CoA:cholesterol acyltransferase in cell extracts. Polyoxyethylated cholesterol had no effect on the low level of LDL receptor activity of homozygous hypercholesterolemic fibroblasts but stimulated the half-normal activity of heterozygous cells.
在来自正常和纯合子家族性高胆固醇血症患者的培养皮肤成纤维细胞中，一种胆固醇的水溶性聚氧乙烯化衍生物可抑制[2-¹⁴C]乙酸掺入胆固醇，并降低3-羟基-3-甲基戊二酰辅酶A还原酶（胆固醇合成的限速酶）的活性。将该化合物对低密度脂蛋白（LDL）受体介导的活性（LDL的结合、内化和降解）以及对胆固醇酯形成的影响与LDL和25-羟胆固醇的影响进行了比较。在缺乏脂蛋白的血清中预孵育的正常成纤维细胞中，LDL或25-羟胆固醇可降低胆固醇合成和LDL受体活性，并增加胆固醇酯形成。相反，聚氧乙烯化胆固醇刺激LDL受体活性，抑制由LDL和25-羟胆固醇介导的胆固醇酯形成，并抑制细胞提取物中酰基辅酶A：胆固醇酰基转移酶的活性。聚氧乙烯化胆固醇对纯合子高胆固醇血症成纤维细胞的低水平LDL受体活性没有影响，但刺激杂合子细胞的半正常活性。
