Reimann F M, Herold G, Grosshans I, Rogler G, Fellermann K, Stange E F
Department of Internal Medicine II, University of Ulm, FRG.
Digestion. 1992;51(1):10-7. doi: 10.1159/000200870.
In the present paper, the regulation of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, acylcoenzyme A cholesterol acyltransferase (ACAT) and low-density lipoprotein (LDL) binding was studied in the human colon cancer carcinoma cell line Caco-2. LDL down-regulated HMG-CoA reductase activity in a dose-dependent fashion to a minimum of 28% of control at 200 micrograms/ml and LDL binding to 52% of control. The activity of ACAT was stimulated by LDL. High-density lipoprotein 3 (HDL3) increased HMG-CoA reductase activity, whereas cholesteryl ester formation was slightly decreased. Inhibition of the endogenous cholesterol biosynthesis by mevinolin increased both LDL binding and activity of HMG-CoA reductase. This effect was reversed by the addition of mevalonolactone but not by LDL. It is concluded that regulation of HMG-CoA reductase and LDL binding is subject to the availability of non-sterol products of mevalonic acid and of exogenous cholesterol. ACAT is regulated mainly by the level of its substrate cholesterol.
在本论文中，对人结肠癌细胞系Caco-2中3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶、酰基辅酶A胆固醇酰基转移酶（ACAT）以及低密度脂蛋白（LDL）结合的调节进行了研究。LDL以剂量依赖方式下调HMG-CoA还原酶活性，在200微克/毫升时降至对照的最低28%，且LDL结合降至对照的52%。LDL刺激ACAT的活性。高密度脂蛋白3（HDL3）增加HMG-CoA还原酶活性，而胆固醇酯形成略有减少。美伐他汀对内源性胆固醇生物合成的抑制增加了LDL结合以及HMG-CoA还原酶的活性。添加甲羟戊酸内酯可逆转此效应，但LDL不能。结论是，HMG-CoA还原酶和LDL结合的调节取决于甲羟戊酸的非甾醇产物和外源性胆固醇的可用性。ACAT主要受其底物胆固醇水平的调节。
