title: Uptake and metabolism of lipoprotein-X in mesangial cells.
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 the 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: E G
authors.initials: EG
authors.lastname: Lynn
authors.forename: P C
authors.initials: PC
authors.lastname: Choy
authors.forename: A
authors.initials: A
authors.lastname: Magil
authors.forename: K
authors.initials: K
authors.lastname: O
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000494:pharmacology / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology / Q000502:physiology; D002855:Chromatography, Thin Layer; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D008073:Lipoprotein-X / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008074:Lipoproteins / Q000494:pharmacology / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012588:Scintillation Counting
chemical_list: D001053:Apolipoproteins; D008073:Lipoprotein-X; D008074:Lipoproteins; D010713:Phosphatidylcholines; D002784:Cholesterol