Differing effects of three oxysterols on low density lipoprotein metabolism in HepG2 cells.
Differing effects of three oxysterols on low density lipoprotein metabolism in HepG2 cells.
复制标题
三种氧甾醇对 HepG2 细胞低密度脂蛋白代谢的不同影响。
DOI：
10.1006/bbrc.1993.1737
复制
发表时间：
1993
影响因子：
3.1
通讯作者：
SchroepferJr,GJ
中科院分区：
文献类型：
--
作者：
Pinkerton,FD;Spilman,CH;Via,DP;SchroepferJr,GJ
（25 R）-26-羟基胆固醇、25-羟基胆固醇和3β-羟基-5 α-胆甾-8（14）-烯-15-酮是哺乳动物细胞中甾醇合成和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶活性的强效抑制剂，本文研究了它们对人肝癌细胞（HepG 2）低密度脂蛋白（LDL）代谢的影响。这三种氧化固醇对LDL代谢的影响差异显着，细胞相关加上degraded 125 I-LDL的组合测量。浓度为0.1 μM至75 μM的26-羟基甾醇可降低LDL代谢。相比之下，25-羟基甾醇和15-酮甾醇在0.05 μM至2.5 μM的浓度下引起LDL代谢的增加。在较高浓度的这些氧化固醇，LDL代谢受到抑制。然而，当15-酮甾醇的浓度进一步增加至75 μM时，观察到LDL代谢异常增加9倍。与它们对LDL代谢的影响相反，在相同条件下，25-羟基甾醇和15-酮甾醇引起HMG-CoA还原酶活性水平的简单浓度依赖性降低。
(25R)-26-Hydroxycholesterol, 25-hydroxycholesterol, and 3β-hydroxy-5α-cholest-8(14)-en-l5-one, all extraordinarily potent suppressors of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in mammalian cells, have been studied with respect to their effects on the metabolism of low density lipoproteins (LDL) by human hepatocarcinoma (HepG2) cells. The three oxysterols differed markedly in their effects on LDL metabolism, as measured by the combination of cell-associated plus degraded125I-LDL. The 26-hydroxysterol, at concentrations from 0.1 μM to 75 μM, lowered LDL metabolism. In contrast, the 25-hydroxysterol and the 15-ketosterol, at concentrations from 0.05 μM to 2.5 μM, caused an increase in LDL metabolism. At higher concentrations of these oxysterols, LDL metabolism was suppressed. However, upon increasing the concentration of the 15-ketosterol further to 75 μM, an extraordinary 9-fold increase in LDL metabolism was observed. In contrast to their effects on LDL metabolism, the 25-hydroxysterol and the 15-ketosterol caused simple concentration-dependent decreases in the levels of HMG-CoA reductase activity under the same conditions.