Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities.
Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities.
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发表时间：
1992-12
影响因子：
6.5
通讯作者：
S. Kunitake;C. Mendel;L. Hennessy
中科院分区：
文献类型：
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作者：
S. Kunitake;C. Mendel;L. Hennessy
基于电泳迁移率的差异，含载脂蛋白（apo）A-I的脂蛋白可以分为两个亚组分，前β HDL和α HDL（高密度脂蛋白）。在这份报告中，我们提出的结果表明，这两个亚组分的代谢联系。当血浆在37 ℃下孵育2小时时，具有前β电泳迁移率的apoA-I质量消失。在孵育前，向血浆中加入1.4 mM DTNB或10 mM薄荷醇可阻断apoA-I质量向α电泳迁移率的这种转变，表明卵磷脂：胆固醇酰基转移酶（LCAT）活性参与其中。有没有变化的电泳迁移率的前β HDL或α HDL时，他们与胆固醇负载的成纤维细胞孵育。然而，在暴露于成纤维细胞后，前β HDL的胆固醇含量确实增加了约六倍，表明前β HDL可以与可观量的细胞胆固醇相关。前β HDL样颗粒似乎是通过α HDL与胆固醇酯转移蛋白（CETP）和极低密度脂蛋白（VLDL）或低密度脂蛋白（LDL）孵育产生的。通过免疫电泳和分子筛色谱法记录了前β HDL样颗粒的产生。基于这些发现，我们提出了一个循环模型，其中1）apoA-I质量从前β HDL移动到α HDL，与LCAT的作用和HDL内胆固醇酯的产生有关，2）apoA-I从α HDL移动到前β HDL，与CETP的作用和胆固醇酯从HDL中移出有关。此外，我们提出，前β HDL和α HDL的相对血浆浓度反映了胆固醇酯通过HDL的运动。导致HDL胆固醇酯蓄积的病症将与低浓度的前β HDL相关，而导致HDL胆固醇酯消耗的病症将与升高浓度的前β HDL相关。这一假设与已发表的高胆固醇血症和LCAT缺乏症患者的研究结果一致。
Apolipoprotein (apo) A-I-containing lipoproteins can be separated into two subfractions, pre-beta HDL and alpha HDL (high density lipoproteins), based on differences in their electrophoretic mobility. In this report we present results indicating that these two subfractions are metabolically linked. When plasma was incubated for 2 h at 37 degrees C, apoA-I mass with pre-beta electrophoretic mobility disappeared. This shift in apoA-I mass to alpha electrophoretic mobility was blocked by the addition of either 1.4 mM DTNB or 10 mM menthol to the plasma prior to incubation, suggesting that lecithin:cholesterol acyltransferase (LCAT) activity was involved. There was no change in the electrophoretic mobility of either pre-beta HDL or alpha HDL when they were incubated with cholesterol-loaded fibroblasts. However, after exposure to the fibroblasts, the cholesterol content of the pre-beta HDL did increase approximately sixfold, suggesting that pre-beta HDL can associate with appreciable amounts of cellular cholesterol. Pre-beta HDL-like particles appear to be generated by the incubation of alpha HDL with cholesteryl ester transfer protein (CETP) and either very low density lipoproteins (VLDL) or low density lipoproteins (LDL). This generation of pre-beta HDL-like particles was documented both by immunoelectrophoresis and by molecular sieve chromatography. Based on these findings, we propose a cyclical model in which 1) apoA-I mass moves from pre-beta HDL to alpha HDL in connection with the action of LCAT and the generation of cholesteryl esters within the HDL, and 2) apoA-I moves from alpha HDL to pre-beta HDL in connection with the action of CETP and the movement of cholesteryl esters out of the HDL. Additionally, we propose that the relative plasma concentrations of pre-beta HDL and alpha HDL reflect the movement of cholesteryl esters through the HDL. Conditions that result in the accumulation of HDL cholesteryl esters will be associated with low concentrations of pre-beta HDL, whereas conditions that result in the depletion of HDL cholesteryl esters will be associated with elevated concentrations of pre-beta HDL. This postulate is consistent with published findings in patients with hypertriglyceridemia and LCAT deficiency.