Role of chondroitin sulphate in the uptake of beta-VLDL by brain cells.
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 (beta-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-beta-VLDL uptake. We showed that externally added CSs compete with internalization of beta-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, 3H-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.
Rapp
Alfred
A
MedUniWien, Center of Physiology and Pathophysiology, Department of Medical Chemistry, Währingerstrasse 10, 1090 Vienna, Austria. alfredapp@yahoo.com
Hüttinger
Manfred
M
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D015151:Immunoblotting; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D018110:Receptors, Lipoprotein / Q000096:biosynthesis; D013050:Spectrometry, Fluorescence
D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D018110:Receptors, Lipoprotein; D002809:Chondroitin Sulfates; D002784:Cholesterol; D019765:Chondroitin ABC Lyase