Chait A, Eisenberg S, Steinmetz A, Albers J J, Bierman E L
Biochim Biophys Acta. 1984 Sep 12;795(2):314-25. doi: 10.1016/0005-2760(84)90081-x.
Low-density lipoproteins (LDL) were modified by incubation with very-low-density lipoproteins (VLDL) and lipid transfer protein(s) to yield LDL particles that were enriched in triacylglycerol, depleted in cholesteryl esters, and contained apolipoprotein C. The uptake and degradation of these 125I-labeled modified LDL particles by cultured skin fibroblasts was reduced by approx. 30% when compared with LDL that had not been exposed to lipid transfer protein. Incubation of fibroblasts for 24 h in the presence of modified LDL resulted in less inhibition of LDL receptor activity and sterol synthesis than did incubation with control LDL. Both the degradation of 125I-labeled modified LDL and the effect of unlabeled modified LDL on the regulation of LDL binding and sterol synthesis were progressively decreased as the extent of modification of the LDL was increased. Even when identical amounts of modified LDL or control LDL protein were degraded, less inhibition of LDL receptor activity and sterol synthesis was observed with modified LDL than with control LDL, suggesting that the effects of modified LDL on these regulatory events are related to both the reduced degradation of the modified lipoprotein particles and to the alteration in its chemical composition. Uptake and degradation of modified LDL by human monocyte-derived macrophages in culture was reduced in a manner similar to that observed in the cultured fibroblasts, and was considerably less than that observed with acetylated LDL. No differences were observed between modified LDL prepared by exposure to lipid transfer activity in the lipoprotein deficient fraction of serum or when partially purified lipid transfer was used. Modified LDL, with similar composition to that used in the experiments, has been observed in certain diabetic and non-diabetic hypertriglyceridemic states. Thus, it is possible that the cellular metabolism of LDL in vivo might be altered in the presence of hypertriglyceridemia.
低密度脂蛋白（LDL）与极低密度脂蛋白（VLDL）及脂质转运蛋白一起孵育，从而得到富含三酰甘油、胆固醇酯减少且含有载脂蛋白C的LDL颗粒，对其进行修饰。与未接触脂质转运蛋白的LDL相比，培养的皮肤成纤维细胞对这些125I标记的修饰LDL颗粒的摄取和降解减少了约30%。在修饰LDL存在的情况下，将成纤维细胞孵育24小时，与对照LDL孵育相比，LDL受体活性和固醇合成的抑制作用较小。随着LDL修饰程度的增加，125I标记的修饰LDL的降解以及未标记的修饰LDL对LDL结合和固醇合成调节的作用均逐渐降低。即使修饰LDL或对照LDL蛋白降解的量相同，与对照LDL相比，修饰LDL对LDL受体活性和固醇合成的抑制作用也较小，这表明修饰LDL对这些调节事件的影响既与修饰脂蛋白颗粒降解减少有关，也与其化学成分的改变有关。培养的人单核细胞衍生巨噬细胞对修饰LDL的摄取和降解减少，其方式与培养的成纤维细胞中观察到的相似，且明显低于乙酰化LDL的摄取和降解。在血清脂蛋白缺陷部分中通过暴露于脂质转运活性制备的修饰LDL与使用部分纯化的脂质转运蛋白制备的修饰LDL之间未观察到差异。在某些糖尿病和非糖尿病高甘油三酯血症状态下已观察到与实验中使用的组成相似的修饰LDL。因此，在高甘油三酯血症存在的情况下，体内LDL的细胞代谢可能会发生改变。
