ApoE of the HepG2 Cell Surface Includes a Major Pool Associated with Chondroitin Sulfate Proteoglycans

Burgess, Jim W.; Liang, Ping; Vaidyanath, Chantal; Marcel, Yves L.

doi:10.1021/bi9819778

Cited by 16Proteoglycans and glycosaminoglycans researchAlzheimer's disease research and treatmentsCholesterol and Lipid Metabolism

ApoE of the HepG2 Cell Surface Includes a Major Pool Associated with Chondroitin Sulfate Proteoglycans

Burgess, Jim W., Liang, Ping, Vaidyanath, Chantal, Marcel, Yves L.·1999·Biochemistry

DOI 10.1021/bi9819778

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Abstract

We have investigated the association of apolipoprotein E (apoE) with the HepG2 cell surface (i.e. plasma membrane and extracellular matrix) using domain specific monoclonal antibodies against apoE. Growth in beta-D-xyloside decreased the incorporation of 35S into glycosaminoglycans by 31% and cell surface apoE by 45% with a concomitant increase in apoE secretion (4.3-fold), underlining the importance of glycosaminoglycan association of apoE. Heparinase (3-10 U/mL) or heparin (1 mg/mL) decreased apoE by 25 and 30.5%, respectively, which suggests that some apoE is associated with cell surface heparan sulfate proteoglycans. Chondroitinase ABC (1.5 U/mL) reduced cell surface apoE by 40%, indicating that a major pool of apoE is associated with chondroitin sulfate proteoglycans. Further enzymatic and displacement analysis suggested that cell surface apoE associates specifically with GAGs containing chondroitin-4-sulfates. 3H1, a monoclonal antibody that recognizes an epitope within the lipid-binding C-terminal domain of apoE, decreased binding of apoE to chondroitin sulfate proteoglycans in solid-phase assays by 77% and to heparan sulfate proteoglycans by 46%, suggesting that this region is of increased importance for binding to chondroitin sulfate proteoglycans. Previous studies with 3H1 demonstrated that apoE of the extracellular matrix is lipid-poor (Burgess, J. W., Gould, D. R., and Marcel, Y. L. (1998) J. Biol. Chem. 273, 5645-5654), but we show here that apoE on the remaining cell surface is lipid-associated. In summary, lipidated apoE associates with the HepG2 plasma membrane through interactions with chondroitin-4-sulfate containing GAGs and, to a lesser extent, HSPG.

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The binding of apoE to cell-surface glycosaminoglycans (GAG) such as chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans plays an important role in lipoprotein catabolism.
“Besides the apoE-HSPG interaction, the binding of apoE to cell-surface glycosaminoglycans (GAG) such as chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans has been demonstrated to play an important role in lipoprotein catabolism.”
From Role of the N- and C-Terminal Domains in Binding of Apolipoprotein E Isoforms to Heparan Sulfate and Dermatan Sulfate: A Surface Plasmon Resonance Study (2008) · cites this paper as [13]

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Dynamic and stable pools of apoE differ functionally at the HepG2 cell surface
Burgess, J. W., & Marcel, Y. L. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30273-x · Cited by 8 · see citing works
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[Relationship between proteoglycans and apoE on the HepG2 cell surface].
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Authors: Burgess, J. W., Liang, P., Vaidyanath, C., & Marcel, Y. L.
Affiliations: Ottawa Heart Institute (CA)
Corresponding author: Marcel, Yves L.
ORCID: Vaidyanath, Chantal
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 1998-12-19
Volume: 38
Issue: 2
Pages: 524-531
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/bi9819778
OpenAlex: W1990717706
Cited by: 16
References: 30
Citations by year: 2026: 1 · 2024: 1 · 2020: 1 · 2019: 1
FWCI: 0.72
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Abbott Laboratories
Eli Lilly and Company
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords: apolipoprotein E, HepG2 cells, cell surface, chondroitin sulfate proteoglycans, heparan sulfate proteoglycans, glycosaminoglycans, chondroitin 4-sulfate, lipid modification, plasma membrane, extracellular matrix, apoE secretion, heparinase, chondroitinase ABC
MeSH terms: Apolipoproteins E, Cell Membrane, Glycosaminoglycans, Heparin, Carcinoma, Hepatocellular, Humans, Hymecromone, Chondroitin Sulfate Proteoglycans, Sulfates, Suramin, Tumor Cells, Cultured, Protein Structure, Tertiary, Lipid Metabolism

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ApoE of the HepG2 Cell Surface Includes a Major Pool Associated with Chondroitin Sulfate Proteoglycans

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