Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes.
نویسندگان
چکیده
Circulating human lymphocytes freshly isolated from venous blood of 15 normal subjects exhibited a low capacity to bind, take up, and degrade 125I-labeled low density lipoprotein (LDL). However, when these cells were incubated for 72 h in the absence of lipoproteins, they gradually acquired in increased number of high affinity cell surface receptors for LDL. The increase in the number of LDL receptors was associated with a 16-fold increase in the rate at which the cells were able to take up and degrade the lipoprotein. The LDL binding and degradation processes that developed in normal lymphocytes exhibited the following characteristics; (a) high affinity (saturation was achieved at LDL concentrations below 50 mug protein/ml); (b) specificity (unlabeled LDL was much more effective than human high density lipoprotein or other plasma proteins in competing with 125I-LDL for binding to the LDL receptor); and(c) feedback regulation (the increase in the number of LDL receptors that appeared after incubation of freshly isolated lymphocytes in lipoprotein-deficient medium was prevented by exposure of the cells to either LDL or a mixture of 25-hydroxycholesterol plus cholesterol but not to HDL). Freshly isolated lymphocytes obtaine from three subjects with the homozygous form of familial hypercholesterolemia failed to develop normal amounts of LDL receptor activity when incubated in medium devoid of lipoproteins. The current data indicate: (a) that the LDL receptors that appear on the surface of cholesterol-deprived, normal human lymphocytes are genetically identical to the previously characterized LDL receptors of cultured human fibroblasts and long-term lymphoid cells and (b) that at least one cell type in the human body, the circulating human lymphocyte, has the capacity to produce a high affinity LDL receptor that mediates the cellular uptake and degradation of plasma LDL.
منابع مشابه
Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes
The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were ...
متن کاملRegulation of low density lipoprotein receptor gene expression in human lymphocytes.
Cholesterol homeostasis is maintained by coordinate regulation of endogenous synthesis and exogenous uptake of lipoprotein cholesterol by low density lipoprotein (LDL) receptors. In the lymphocyte, limiting the availability of exogenous cholesterol is known to increase the rate of endogenous sterol biosynthesis. However, the effect of cholesterol deprivation on the expression and regulation of ...
متن کاملAutoregulation of the modified low density lipoprotein receptor in human monocyte-derived macrophages.
Regulation of the macrophage receptor for modified low density lipoprotein (LDL) was evaluated using human monocyte-derived macrophages and acetyl LDL. Factors that regulate native LDL receptor activity in other cell types, such as the cholesterol content of the incubation medium, insulin, and platelet-derived growth factor had no effect on acetyl LDL degradation. Conditioned medium from mature...
متن کاملImproved detection of familial hypercholesterolemia by determining low density lipoprotein receptor expression in mitogen-induced proliferating lymphocytes.
In view of the presence of some 190 mutations in the low density lipoprotein receptor (LDL-R) gene and a lack of simple detection methods, we have developed an improved assay system for detecting familial hypercholesterolemia (FH) using mitogen-induced proliferating lymphocytes. Freshly isolated mononuclear cells were cultured for 3 days in RPMI 1640 supplemented with 10% human lipoprotein-defi...
متن کاملDifferential regulation of the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, synthase, and low density lipoprotein receptor genes.
The ability of mitogenic stimulation of human T lymphocytes to alter the expression of genes involved in sterol metabolism was examined. Messenger RNA levels for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, HMG-CoA synthase, and low density lipoprotein (LDL) receptor were quantified in resting and mitogen-stimulated T lymphocytes by nuclease protection assay. Mitogenic stimulation...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 58 6 شماره
صفحات -
تاریخ انتشار 1976