Apolipoprotein C-I modulates the interaction of apolipoprotein E with β-migrating very low density lipoproteins (β-VLDL) and inhibits binding of β-VLDL to low density lipoprotein receptor-related protein

Karl H. Weisgraber, Robert W. Mahley, Robert C. Kowal, Joachim Herz, Joseph L. Goldstein, Michael S. Brown

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Abstract

The binding of native rabbit β-very low density lipoproteins (β-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of β- VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit β-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the β-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the β-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the β-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP.

Original languageEnglish (US)
Pages (from-to)22453-22459
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number36
StatePublished - Dec 25 1990

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Apolipoprotein C-I
LDL-Receptor Related Proteins
Apolipoproteins C
VLDL Lipoproteins
LDL Receptors
Apolipoproteins E
Lipoprotein Receptors
Apolipoprotein C-III
Proteins
Rabbits
Cholesterol Esters
Fibroblasts
Electrophoresis
Sodium Dodecyl Sulfate
Gel Chromatography
Polyacrylamide Gel Electrophoresis

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{caf91de92af44a149aedad5a53188ee0,
title = "Apolipoprotein C-I modulates the interaction of apolipoprotein E with β-migrating very low density lipoproteins (β-VLDL) and inhibits binding of β-VLDL to low density lipoprotein receptor-related protein",
abstract = "The binding of native rabbit β-very low density lipoproteins (β-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of β- VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit β-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the β-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the β-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the β-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP.",
author = "Weisgraber, {Karl H.} and Mahley, {Robert W.} and Kowal, {Robert C.} and Joachim Herz and Goldstein, {Joseph L.} and Brown, {Michael S.}",
year = "1990",
month = "12",
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language = "English (US)",
volume = "265",
pages = "22453--22459",
journal = "Journal of Biological Chemistry",
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T1 - Apolipoprotein C-I modulates the interaction of apolipoprotein E with β-migrating very low density lipoproteins (β-VLDL) and inhibits binding of β-VLDL to low density lipoprotein receptor-related protein

AU - Weisgraber, Karl H.

AU - Mahley, Robert W.

AU - Kowal, Robert C.

AU - Herz, Joachim

AU - Goldstein, Joseph L.

AU - Brown, Michael S.

PY - 1990/12/25

Y1 - 1990/12/25

N2 - The binding of native rabbit β-very low density lipoproteins (β-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of β- VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit β-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the β-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the β-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the β-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP.

AB - The binding of native rabbit β-very low density lipoproteins (β-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of β- VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit β-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the β-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the β-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the β-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP.

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