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Uptake and metabolism of lipoprotein-X in mesangial cells

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Abstract

Progressive glomerulosclerosis is a major complication in patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. The lack of LCAT activity results in the accumulation of an abnormal lipoprotein, lipoprotein-X (Lp-X), in the plasma of these patients. Lipoprotein-X contains high levels of unesterified cholesterol and phosphatidylcholine. Lp-X may play a role in the accumulation of lipids in the kidney, which in turn may lead to glomerulosclerosis. The objective of this study is to examine the uptake and metabolism of Lp-X by rat mesangial cells. Our results suggest that Lp-X is taken up by mesangial cells and that the lipids in Lp-X are metabolized. Lysosomes containing unesterified cholesterol and phosphatidylcholine, in a molar ratio similar to Lp-X, were synthesized to investigate the roles individual apolipoproteins (apo CI, II, III and E) play in the uptake of Lp-X. Both apo CI and CIII inhibited its uptake while apo CII (1.5 fold) and E (4 fold) stimulated t he uptake of Lp-X. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) inhibited Lp-X uptake by mesangial cells. However, at higher concentrations of high density lipoprotein (HDL), the uptake of Lp-X was stimulated. Proteoglycans have an important role in regulating the uptake of Lp-X, while cytoskeleton-dependent phagocytosis and the scavenger receptor do not appear to be involved. (Mol Cell Biochem 175: 187–194, 1997)

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

    Edward G. Lynn, Alexander Magil & O Karmin

  2. Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Manitoba, Canada

    Patrick C. Choy

  3. Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong

    O Karmin

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  1. Edward G. Lynn
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  2. Patrick C. Choy
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  3. Alexander Magil
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  4. O Karmin
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Lynn, E.G., Choy, P.C., Magil, A. et al. Uptake and metabolism of lipoprotein-X in mesangial cells. Mol Cell Biochem 175, 187–194 (1997). https://doi.org/10.1023/A:1006865420286

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