Degradation by cultured fibroblasts and macrophages of unmodified and 1,2-cyclohexanedione-modified low-density lipoprotein from normal and homozygous familial hypercholesterolaemic subjects.
Degradation by cultured fibroblasts and macrophages of unmodified and 1,2-cyclohexanedione-modified low-density lipoprotein from normal and homozygous familial hypercholesterolaemic subjects.
复制标题
来自正常和纯合家族性高胆固醇血症受试者的未修饰和 1,2-环己二酮修饰的低密度脂蛋白被培养的成纤维细胞和巨噬细胞降解。
DOI：
10.1042/bj2020145
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
A. Soutar
中科院分区：
文献类型：
--
作者：
B. Knight;A. Soutar
使用人皮肤成纤维细胞和单核细胞来源的巨噬细胞的单层培养物来检查环己烷-1,2-二酮修饰对来自正常受试者（NLDL）和纯合家族性高胆固醇血症受试者（FHLDL）的125I标记的低密度脂蛋白（LDL）的蛋白水解降解的影响。在缺乏脂蛋白的血清中预孵育的正常成纤维细胞和在全血清中预孵育的巨噬细胞表现出LDL的饱和和非饱和降解。在成纤维细胞中，可饱和受体介导的 FHLDL 降解与 NLDL 相似，如果用环己二酮修饰脂蛋白，则可消除该降解。 FHLDL 的不饱和降解率比 NLDL 至少高 3 倍，并且各自降低约 10%。修改后60%。在巨噬细胞中，可饱和降解减少但并未通过修饰消除。对未修饰 LDL 的表观亲和力低于对成纤维细胞受体的表观亲和力，对 NLDL 的表观亲和力大于对 FHLDL 的表观亲和力。巨噬细胞对 FHLDL 的非饱和降解仅略高于 NLDL。环己二酮修饰使 NLDL 的不饱和降解率降低了 30%，但使 FHLDL 的不饱和降解率提高了 75%。这些实验显示 125I 标记的 NLDL 和 FHLDL 的降解之间存在差异。他们认为，巨噬细胞可以通过可饱和过程降解 LDL，其特性与成纤维细胞受体介导的过程不同，并且在体外，修饰的 LDL 的降解速率与非受体介导的未修饰 LDL 的降解速率不同。
Monolayer cultures of human skin fibroblasts and monocyte-derived macrophages were used to examine the effect of cyclohexane-1,2-dione modification on the proteolytic degradation of 125I-labelled low-density lipoprotein (LDL) from normal subjects (NLDL) and homozygous familial hypercholesterolaemic subjects (FHLDL). Normal fibroblasts, pre-incubated in lipoprotein-deficient serum, and macrophages, pre-incubated in whole serum, exhibited both saturable and non-saturable degradation of LDL. In fibroblasts, the saturable receptor-mediated degradation of FHLDL was similar to that of NLDL and was abolished if the lipoproteins were modified with cyclohexanedione. The rate of non-saturable degradation of FHLDL was at least 3-fold higher than that of NLDL and each was decreased by approx. 60% after modification. In macrophages, saturable degradation was decreased but not abolished by modification. The apparent affinity for unmodified LDL was lower than that of the fibroblast receptor and was greater for NLDL than for FHLDL. Non-saturable degradation of FHLDL by macrophages was only slightly higher than that of NLDL. Modification with cyclohexanedione decreased the rate of non-saturable degradation of NLDL by 30%, but increased that of FHLDL by 75%. These experiments show differences between the degradation of 125I-labelled NLDL and FHLDL. They suggest that macrophages can degrade LDL by a saturable process with different properties from that mediated by the fibroblast receptor and that, in vitro, the rate of degradation of the modified LDL is not the same as the rate of non-receptor-mediated degradation of unmodified LDL.