Regulation of low density lipoprotein receptors by plasma lipoproteins from patients with abetalipoproteinemia.
Regulation of low density lipoprotein receptors by plasma lipoproteins from patients with abetalipoproteinemia.
复制标题
无β脂蛋白血症患者血浆脂蛋白对低密度脂蛋白受体的调节。
DOI：
10.1073/pnas.80.11.3475
复制
发表时间：
1983
影响因子：
11.1
通讯作者：
Layman,DL
中科院分区：
文献类型：
--
作者：
Illingworth,DR;Alam,NA;Sundberg,EE;Hagemenas,FC;Layman,DL
尽管血浆中不存在低密度脂蛋白（LDL）和乳糜微粒残留物，但来自无β脂蛋白血症患者的新鲜分离细胞上的胆固醇合成率或表达的LDL受体数量并未显着增加。这些观察结果表明，无β脂蛋白血症患者血浆中存在的其他脂蛋白颗粒可能调节这种疾病中的LDL受体活性和细胞胆固醇合成速率。在本报告中，我们研究了正常受试者、无β脂蛋白血症患者和异常β脂蛋白血症患者血浆中的脂蛋白组分对培养的人成纤维细胞结合、内化和降解125I标记的低密度脂蛋白（125I-LDL）的影响。来自正常受试者的 LDL 或来自无β脂蛋白血症患者血浆的高密度脂蛋白部分 HDL2 有效下调 LDL 受体活性（每毫升 20 微克蛋白质的抑制率大于 50%）。无β脂蛋白血症患者血浆中的HDL2也能有效减少培养的人成纤维细胞对125I-LDL的结合、内化和降解。来自无β脂蛋白血症患者血浆的125I-HDL2被培养的人成纤维细胞结合、内化和降解；这一过程受到无β脂蛋白血浆中未标记的正常LDL或HDL2的竞争性抑制，并且当125I-HDL2与来自受体阴性纯合家族性高胆固醇血症患者的成纤维细胞一起孵育时，抑制率是其1/6至1/8倍。我们得出的结论是，无β脂蛋白血症患者血浆HDL2部分中存在的脂蛋白（载脂蛋白E相对丰富）是正常人成纤维细胞中LDL受体活性的有效调节剂。这些体外研究结果可以解释为什么体内胆固醇合成率和来自无β脂蛋白血症患者的新鲜分离细胞上表达的LDL受体数量没有显着增加。
Despite an absence of low density lipoproteins (LDLs) and chylomicron remnants from plasma, the rates of cholesterol synthesis or the number of LDL receptors expressed on freshly isolated cells from patients with abetalipoproteinemia are not markedly increased. These observations suggest that other lipoprotein particles present in the plasma of patients with abetalipoproteinemia may regulate LDL receptor activity and the rates of cellular cholesterol synthesis in this disorder. In the present report we have studied the effects of lipoprotein fractions from the plasma of normal subjects, patients with abetalipoproteinemia, and a patient with dysbetalipoproteinemia on the binding, internalization, and degradation of 125I-labeled LDL (125I-LDL) by cultured human fibroblasts. LDL from normal subjects or the high density lipoprotein fraction HDL2 from the plasma of patients with abetalipoproteinemia effectively down-regulated LDL receptor activity (greater than 50% inhibition at 20 micrograms of protein per ml). HDL2 from the plasma of patients with abetalipoproteinemia also effectively reduced the binding, internalization, and degradation of 125I-LDL by cultured human fibroblasts. 125I-HDL2 from the plasma of patients with abetalipoproteinemia was bound, internalized, and degraded by cultured human fibroblasts; this process was competitively inhibited by unlabeled normal LDL or HDL2 from abetalipoproteinemic plasma and was 1/6th to 1/8th times as high when 125I-HDL2 was incubated with fibroblasts from a patient with receptor-negative homozygous familial hypercholesterolemia. We conclude that lipoproteins present in the HDL2 fraction of plasma from patients with abetalipoproteinemia (which are relatively rich in apoprotein E) are effective regulators of LDL receptor activity in normal human fibroblasts. These in vitro findings may explain why the in vivo rates of cholesterol synthesis and the number of LDL receptors expressed on freshly isolated cells from patients with abetalipoproteinemia are not markedly increased.