EVIDENCE FOR A LIPO PROTEIN CARRIER IN HUMAN PLASMA CATALYZING STEROL EFFLUX FROM CULTURED FIBROBLASTS AND ITS RELATIONSHIP TO LECITHIN CHOLESTEROL ACYL TRANSFERASE EC-2.3.1.43
EVIDENCE FOR A LIPO PROTEIN CARRIER IN HUMAN PLASMA CATALYZING STEROL EFFLUX FROM CULTURED FIBROBLASTS AND ITS RELATIONSHIP TO LECITHIN CHOLESTEROL ACYL TRANSFERASE EC-2.3.1.43
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DOI：
10.1073/pnas.78.6.3911
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发表时间：
1981-01-01
影响因子：
11.1
通讯作者：
FIELDING P E
中科院分区：
文献类型：
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作者：
FIELDING C J;FIELDING P E
用免疫亲和层析法研究了培养的成纤维细胞向人血浆培养上清液中甾醇外流和净转运的决定因素。甾醇外流高度(apprxeq.80%)依赖于含有载脂蛋白A-I的少量脂蛋白，与其他载脂蛋白无关。剩余的活性与血浆中无脂蛋白的部分有关，并可被无载脂蛋白的白蛋白取代。外排与卵磷脂：胆固醇酰基转移酶(LCAT)活性无关。净转运(即外流超过内流)可被抑制LCAT或用固定的载脂蛋白A-I或D(人血浆中转移复合体的组成部分)的亲和层析去除而完全抑制。在不受抑制的血浆中，外排和净转运速率具有相似的动力学，这表明这些是相互关联的功能，净转运是由载体依赖的外排步骤启动的，在没有LCAT活性的情况下，与等量的游离固醇进入细胞有关，在LCAT存在的情况下，与酯化和转移蛋白活性有关。胆固醇载脂蛋白功能(apprxeq.5%的血浆载脂蛋白A-I)似乎是LCAT连接的甾醇从细胞转运的第一步。
Immunoaffinity chromatography was used to study the determinants of sterol efflux and net transport from cultured fibroblasts to human plasma medium. Sterol efflux was highly (.apprxeq. 80%) dependent upon a minor lipoprotein fraction containing apolipoprotein A-I unassociated with other apolipoproteins. The remaining activity was associated with the lipoprotein-free fraction of plasma and could be replaced by apoprotein-free albumin. Efflux was independent of lecithin:cholesterol acyltransferase (LCAT) activity. Net transport (i.e., the excess of efflux over influx) was completely inhibited by inhibition of LCAT or its removal by affinity chromatography on immobilized antibodies to apolipoprotein A-I or D (components of the transfer complex in human plasma). In uninhibited plasma, efflux and net transport rates had similar kinetics, suggesting that these were linked functions and that net transport was initiated by a carrier-dependent efflux step that, in the absence of LCAT activity, was associated with an equivalent influx of free sterol to the cells and that, in the presence of LCAT, was associated with esterification and transfer protein activity. The cholesterol carrier lipoprotein function (.apprxeq. 5% of plasma apolipoprotein A-I) appears to be the 1st step of LCAT-linked sterol transport from cells.