Brown M S, Dana S E, Goldstein J L
J Biol Chem. 1975 May 25;250(10):4025-7.
Incubation of monolayers of cultured human fibroblasts with oxygenated sterols (25-hydroxycholesterol, 7-ketocholesterol, or 6-ketocholestanol) markedly enhanced the rate at which the cells esterified their endogenous cholesterol and produced an increase in the cellular content of cholesterol esters. The enhanced esterification capacity was associated with an increase in the activity of a membrane-bound fatty acyl-CoA:cholesteryl acyltransferase. Incubation of cells for 5 hours with 5 mug/ml of 25-hydroxycholesterol produced an 8-fold increase in the specific activity of this enzyme when assayed in cell-free extracts. Since the oxygenated sterols that elevated the activity of fatty acyl-CoA:cholesteryl acyl-transferase also suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the data suggest that the processes of cholesterol ester formation and cholesterol synthesis in human fibroblasts are regulated in a reciprocal manner by coordinate changes in the activities of these two membrane-bound enzymes.
用氧化固醇（25-羟基胆固醇、7-酮胆固醇或6-酮胆甾烷醇）孵育培养的人成纤维细胞单层，显著提高了细胞将其内源性胆固醇酯化的速率，并使细胞胆固醇酯含量增加。酯化能力的增强与膜结合的脂肪酰辅酶A：胆固醇酰基转移酶活性的增加有关。当在无细胞提取物中进行测定时，用5微克/毫升的25-羟基胆固醇孵育细胞5小时，该酶的比活性增加了8倍。由于提高脂肪酰辅酶A：胆固醇酰基转移酶活性的氧化固醇也抑制了3-羟基-3-甲基戊二酰辅酶A还原酶的活性，数据表明人成纤维细胞中胆固醇酯形成和胆固醇合成过程通过这两种膜结合酶活性的协调变化以相互的方式受到调节。
