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Cited by 1,123

Binding and Degradation of Low Density Lipoproteins by Cultured Human Fibroblasts

Goldstein, Joseph L., Brown, Michael S.·1974·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(19)42341-7
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Abstract

125I-Labeled low density lipoproteins were found to associate with monolayers of cultured normal fibroblasts by two processes—one of high affinity and one of low affinity. The high affinity association appeared to represent binding of the low density lipoprotein to specific receptor sites on the cell surface. This binding process exhibited saturation kinetics at low concentrations of the lipoprotein and competition by related molecules such as very low density lipoproteins. In addition, this process was stimulated by the presence of calcium in the culture medium and could be destroyed by limited treatment of the cells with pronase. The other process, designated low affinity uptake, may represent nonspecific endocytosis since the uptake was proportional to the lipoprotein concentration in the medium with no apparent saturation and because it showed no competition by very low density lipoproteins, no stimulation by calcium, and no destruction by pronase treatment. The 125I-labeled low density lipoproteins associated with normal cells by either the high or low affinity process were degraded by proteolysis to trichloroacetic acid-soluble material, most of which was 125I-tyrosine. In normal cells, binding of low density lipoproteins to the high affinity membrane receptor sites appears to serve two functions: (a) it results in suppression of the synthesis of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, and (b) it facilita…

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  • Degradation of 125I-LDL was blocked by chloroquine, confirming that it occurred in lysosomes.

    “Degradation was blocked by chloroquine, confirming that it occurred in lysosomes (19).”

    From Last step in the path of LDL cholesterol from lysosome to plasma membrane to ER is governed by phosphatidylserine (2020) · cites this paper as [19]

  • The LDLR peptide has an N-terminal ligand binding domain with high affinity for Apolipoprotein E and Apolipoprotein B, the main structural components of VLDL/LDL.

    “The LDLR peptide has an N-terminal ligand binding domain which has high affinity for Apolipoprotein E74,75, as well as Apolipoprotein B (ApoB)76, the main structural components of VLDL/LDL.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [74]

  • Brown and Goldstein demonstrated that fibroblasts from healthy individuals can bind and internalize radiolabeled LDL particles, while fibroblasts from patients with familial hypercholesterolemia cannot.

    “The concept that LDL was brought into the cell in a receptor-mediated manner (Fig. 6) was confirmed in the 1970s when Brown and Goldstein demonstrated that fibroblasts from healthy individuals can bind and internalize radiolabeled LDL particles, while fibroblasts from patients with familial hypercholesterolemia cannot74.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [74]

Cites

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Research works printed but not linked: 19

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  14. Cuatrecasas, 1971, Proc. Nat. Acad. Sci. U. S. A., 68, 1264, 10.1073/pnas.68.6.1264 · DOI
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Authors
Goldstein, J. L., & Brown, M. S.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1974-08
Volume
249
Issue
16
Pages
5153-5162
ISSN
0021-9258
DOI
10.1016/s0021-9258(19)42341-7
Cited by
1,123
References
0
Language
en
Licence

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