The low density lipoprotein pathway in human fibroblasts

relation between cell surface receptor binding and endocytosis of low density lipoprotein

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45 Citations (Scopus)

Abstract

LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high affinity cell surface receptor. Uptake of LDL by this receptor mediated process permits the cell to acquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor negative form of homozygous familial hypercholesterolemia (FH), the cell surface receptor is functionally absent. The absence of high affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hypercholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.

Original languageEnglish (US)
Pages (from-to)244-257
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volumevol. 275
StatePublished - 1976

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Cell Surface Receptors
Fibroblasts
Endocytosis
LDL Lipoproteins
LDL Receptors
Cholesterol
Hyperlipoproteinemia Type II
Lipoproteins
Hypercholesterolemia
Atherosclerosis
Homozygote
Feedback
Defects
oxidized low density lipoprotein
Cells
Pathway
lipoprotein cholesterol

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "The low density lipoprotein pathway in human fibroblasts: relation between cell surface receptor binding and endocytosis of low density lipoprotein",
abstract = "LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high affinity cell surface receptor. Uptake of LDL by this receptor mediated process permits the cell to acquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor negative form of homozygous familial hypercholesterolemia (FH), the cell surface receptor is functionally absent. The absence of high affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hypercholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.",
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pages = "244--257",
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T1 - The low density lipoprotein pathway in human fibroblasts

T2 - relation between cell surface receptor binding and endocytosis of low density lipoprotein

AU - Brown, M. S.

AU - Ho, Y. K.

AU - Goldstein, J. L.

PY - 1976

Y1 - 1976

N2 - LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high affinity cell surface receptor. Uptake of LDL by this receptor mediated process permits the cell to acquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor negative form of homozygous familial hypercholesterolemia (FH), the cell surface receptor is functionally absent. The absence of high affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hypercholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.

AB - LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high affinity cell surface receptor. Uptake of LDL by this receptor mediated process permits the cell to acquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor negative form of homozygous familial hypercholesterolemia (FH), the cell surface receptor is functionally absent. The absence of high affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hypercholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.

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