洛伐他汀、甲羟戊酸和低密度脂蛋白对人肝癌细胞系Hep G2中3-羟基-3-甲基戊二酰辅酶A还原酶活性及低密度脂蛋白受体活性的影响
Effects of compactin, mevalonate and low-density lipoprotein on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and low-density-lipoprotein-receptor activity in the human hepatoma cell line Hep G2.
作者信息
Cohen L H, Griffioen M, Havekes L, Schouten D, van Hinsbergh V, Kempen H J
出版信息
Biochem J. 1984 Aug 15;222(1):35-9. doi: 10.1042/bj2220035.
Abstract
Compactin, an inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, decreased cholesterol synthesis in intact Hep G2 cells. However, after the inhibitor was washed away, the HMG-CoA-reductase activity determined in the cell homogenate was found to be increased. Also the high-affinity association of LDL (low-density lipoprotein) to Hep G2 cells was elevated after incubation with compactin. Lipoprotein-depleted serum, present in the incubation medium, potentiated the compactin effect compared with incubation in the presence of human serum albumin. Addition of either mevalonate or LDL prevented the compactin-induced rise in activities of both HMG-CoA reductase and LDL receptor in a comparable manner. It is concluded that in this human hepatoma cell line, as in non-transformed cells, both endogenous mevalonate or mevalonate-derived products and exogenous cholesterol are able to modulate the HMG-CoA reductase activity as well as the LDL-receptor activity.
摘要
美伐他汀是3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的抑制剂，可降低完整Hep G2细胞中的胆固醇合成。然而，在洗去抑制剂后，发现细胞匀浆中测定的HMG-CoA还原酶活性增加。此外，与美伐他汀孵育后，Hep G2细胞与低密度脂蛋白（LDL）的高亲和力结合增加。与在人血清白蛋白存在下孵育相比，孵育培养基中存在的无脂蛋白血清增强了美伐他汀的作用。添加甲羟戊酸或LDL以类似方式阻止了美伐他汀诱导的HMG-CoA还原酶和LDL受体活性的升高。得出的结论是，在这种人肝癌细胞系中，与未转化细胞一样，内源性甲羟戊酸或甲羟戊酸衍生的产物以及外源性胆固醇都能够调节HMG-CoA还原酶活性以及LDL受体活性。
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