Martin G G, Shapiro D J
Biochim Biophys Acta. 1985 Nov 14;837(2):163-72. doi: 10.1016/0005-2760(85)90239-5.
A water-soluble derivative of cholesterol, methoxypolyoxyethylated (MPOE) cholesterol, has been synthesized and used to study the regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key regulatory enzyme in cholesterol biosynthesis. MPOE cholesterol causes a specific, rapid and linear decline in HMG-CoA reductase in cultured rat liver cells. MPOE cholesterol is not a direct allosteric inhibitor of HMG-CoA reductase, does not appear to regulate HMG-CoA reductase through changes in membrane environment, and does not change the phosphorylation state and level of activation of rat liver cell HMG-CoA reductase. In order to confirm our data, which were consistent with a model in which MPOE cholesterol regulates the amount of HMG-CoA reductase and not its activity, we made direct measurements of reductase mRNA levels. The decline in HMG-CoA reductase in MPOE cholesterol-treated rat liver cells is preceded by the rapid disappearance of HMG-CoA reductase mRNA. As a water-soluble cholesterol derivative, MPOE cholesterol represents a useful model compound for studies on the regulation of the level of HMG-CoA reductase and its cognate mRNA.
胆固醇的一种水溶性衍生物，甲氧基聚氧乙烯化（MPOE）胆固醇，已被合成并用于研究3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的调节，该酶是胆固醇生物合成中的关键调节酶。MPOE胆固醇导致培养的大鼠肝细胞中HMG-CoA还原酶特异性、快速且呈线性下降。MPOE胆固醇不是HMG-CoA还原酶的直接变构抑制剂，似乎不是通过改变膜环境来调节HMG-CoA还原酶，也不会改变大鼠肝细胞HMG-CoA还原酶的磷酸化状态和激活水平。为了证实我们的数据，这些数据与MPOE胆固醇调节HMG-CoA还原酶的量而非其活性的模型一致，我们直接测量了还原酶mRNA水平。在MPOE胆固醇处理的大鼠肝细胞中，HMG-CoA还原酶的下降之前是HMG-CoA还原酶mRNA的快速消失。作为一种水溶性胆固醇衍生物，MPOE胆固醇是研究HMG-CoA还原酶水平及其同源mRNA调节的有用模型化合物。
