Role of chondroitin sulphate in the uptake of β‐VLDL by brain cells
Abstract
Proteoglycans (PGs) have been suggested to work as receptors in lipoprotein uptake mechanisms. An interaction between apolipoprotein E (apoE) and glucosaminoglycans (GAG), polysaccharides linked to proteoglycans, has been proposed in this pathway. At the same time, proteoglycans, apoE as well as lipoprotein receptors have been reported to be constituents of amyloid plaques, one hallmark of Alzheimer's disease. With this study, we are the first to investigate the interaction between beta very low density lipoprotein (β‐VLDL) and a neuronal highly abundant GAG, chondroitin sulphate (CS), comparing hippocampal neurons, expressing high levels of low density lipoprotein receptor related protein (LRP) and U373 astrocytoma cells, highly positive for the low density lipoprotein receptor (LDLR). We were able demonstrate that degradation of chondroitin sulphate proteoglycans (CSPGs) with chondroitinase ABC resulted in reduced 125 I‐β‐VLDL uptake. We showed that externally added CSs compete with internalization of β‐VLDL. The effect was found to be dose‐dependent, but was influenced neither by cell type, nor receptor type. The position of sulphation of added CSs showed only a slight influence. The data generated suggested an interaction between apolipoproteins and soluble CSs; therefore, 3 H‐cholesterol linked to apoE was coadministered with CSs to the cells. The results revealed that apoE bound, but no unbound cholesterol, was reduced in cellular internalization, suggesting that CSPGs may be involved in lipoprotein uptake in the intact brain, mediated, at least in part, by apoE.
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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 [15]
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- Authors
- Rapp, A., & Hüttinger, M.
- Affiliations
- Medical University of Vienna (AT)
- Corresponding author
- Rapp, Alfred
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2005-09
- Volume
- 22
- Issue
- 6
- Pages
- 1400-1408
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1492604886
- Cited by
- 4
- References
- 43
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- chondroitin sulfate, lipoprotein uptake, proteoglycans, chondroitinase ABC, apolipoprotein E, glycosaminoglycans, LDL receptor, LRP, astrocytes, hippocampal neurons, Alzheimer's disease, amyloid plaques, cholesterol, receptor internalization
- MeSH terms
- Animals, Apolipoproteins E, Astrocytoma, Brain, Brain Chemistry, Cell Line, Cholesterol, Chondroitin Sulfates, Female, Hippocampus, Lipoproteins, VLDL, Neurons, Pregnancy, Spectrometry, Fluorescence, Immunoblotting, Receptors, Lipoprotein, Chondroitin ABC Lyase, Rats
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