Molowa D T, Cimis G M
Department of Molecular Pharmacology and Biochemistry, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Biochem J. 1989 Jun 15;260(3):731-6. doi: 10.1042/bj2600731.
Cellular processes responsible for maintaining cholesterol homoeostasis are highly regulated. To determine whether two of these processes, cholesterol biosynthesis and receptor-mediated uptake of low-density lipoprotein (LDL), are co-ordinately regulated in human liver, we employed a human hepatoma cell line (HepG2) and measured the accumulation of mRNA for LDL receptor, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and HMG-CoA synthase under a variety of conditions. Genomic Southern-blot analysis demonstrated that the integrity of these genes is maintained in the transformed cell. Treatment of HepG2 cells with mevalonate, 25-hydroxycholesterol, LDL, lovastatin or miconazole resulted in a similar effect on the accumulation of all three mRNAs at the concentrations tested. The onset of the response to drug, whether repression or induction of mRNA accumulation, occurred after approximately the same period of exposure for each mRNA. We conclude that the expression of the LDL receptor, HMG-CoA reductase and HMG-CoA synthase is co-ordinately regulated in HepG2 cells.
负责维持胆固醇稳态的细胞过程受到高度调控。为了确定其中两个过程，即胆固醇生物合成和受体介导的低密度脂蛋白（LDL）摄取，在人类肝脏中是否受到协同调控，我们使用了一种人类肝癌细胞系（HepG2），并在各种条件下测量了LDL受体、3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶和HMG-CoA合酶的mRNA积累情况。基因组Southern印迹分析表明，这些基因的完整性在转化细胞中得以维持。用甲羟戊酸、25-羟基胆固醇、LDL、洛伐他汀或咪康唑处理HepG2细胞，在测试浓度下对所有三种mRNA的积累产生了类似的影响。对药物反应的起始，无论是mRNA积累的抑制还是诱导，每种mRNA在大约相同的暴露时间后发生。我们得出结论，在HepG2细胞中，LDL受体、HMG-CoA还原酶和HMG-CoA合酶的表达受到协同调控。
