Quantitative analysis of hydrophobic amine inhibition of intracellular cholesterol transport.
Quantitative analysis of hydrophobic amine inhibition of intracellular cholesterol transport.
复制标题
DOI：
--
复制
发表时间：
1996-07
影响因子：
6.5
通讯作者：
K. Underwood;B. Andemariam;G. L. McWilliams;L. Liscum
中科院分区：
文献类型：
--
作者：
K. Underwood;B. Andemariam;G. L. McWilliams;L. Liscum
U18666 A和丙咪嗪是抑制细胞内胆固醇转运途径的疏水胺。在这项研究中，我们对每种胆固醇转运途径进行了剂量反应曲线。我们的分析表明，疏水性胺抑制LDL刺激的胆固醇酯化是更敏感的抑制比无论是从溶酶体到质膜和从质膜到内质网的胆固醇的组合批量移动。疏水性胺必须抑制一个以前未知的途径，从溶酶体到内质网或激活酰基辅酶A：胆固醇酰基转移酶的信号事件。评估了U18666 A作用的可能机制。参与胆固醇转运的p-糖蛋白的功能不受U18666 A的影响。我们有一个特定的膜U18666 A结合位点的证据，我们假设这是参与质膜到内质网胆固醇转运途径。疏水胺作用的结合位点和机制的鉴定可能为理解细胞内胆固醇转运提供必要的信息。
U18666A and imipramine are hydrophobic amines that inhibit intracellular cholesterol transport pathways. In this study, we conducted dose-response curves for each of the cholesterol transport pathways. Our analyses indicate that hydrophobic amine inhibition of LDL-stimulated cholesterol esterification is much more sensitive to inhibition than either the combined bulk movement of cholesterol from lysosomes to the plasma membrane and from the plasma membrane to the endoplasmic reticulum. Hydrophobic amines must inhibit a previously uncharacterized pathway from lysosomes to the endoplasmic reticulum or a signaling event that activates acyl CoA:cholesterol acyltransferase. Possible mechanisms for U18666A action were evaluated. The function of p-glycoprotein, which has been implicated in cholesterol transport, was unaffected by U18666A. We have evidence for a specific membrane U18666A binding site, which we hypothesize is involved in the plasma membrane to endoplasmic reticulum cholesterol transport pathway. Identification of the binding site and mechanism of hydrophobic amine action may provide information essential for understanding intracellular cholesterol transport.