Heterogeneity of human lipoprotein Lp[a]: cytochemical and biochemical studies on the interaction of two Lp[a] species with the LDL receptor.
Human Lp[a] can be fractionated into two species with different affinities for lysine-Sepharose. Forty to 81% of the total Lp[a] in the density fraction 1.055-1.15 g/ml from five individuals was retained by this affinity column. The remaining unretained Lp[a] species with no apparently functional lysine binding site was similar to the retained species in its electrophoretic mobility, lipid, protein, and apolipoprotein composition, and the heterogeneity was not related to apo[a] size polymorphism. Interaction of the two species with the low density lipoprotein (LDL) receptor was studied in human fibroblasts. Using gold-labeled lipoproteins and an immunochemical procedure, both Lp[a] species could be located in clusters on the cell surface, but the extent of labeling was far lower than that seen with LDL. Both Lp[a] variants were less effective than LDL in 1) down-regulation of LDL-receptor activity; 2) suppression of cellular sterol synthesis; and 3) stimulation of cholesteryl ester formation in human fibroblasts. Although degradation of both species of Lp[a] by the perfused rat liver was stimulated after estrogen induction of hepatic LDL-receptor activity, the stimulation amounted to only a quarter of that seen with LDL. The heterogeneity of Lp[a] with respect to the ability to bind epsilon-aminocarboxylic acid will need to be considered in studying the physiological role of this lipoprotein. Both Lp[a] species exhibited a similar interaction with the LDL-receptor in vitro, and confirmed previous investigations that Lp[a] is only a poor ligand for the LDL-receptor.
Armstrong
V W
VW
Department of Clinical Chemistry, University of Göttingen, FRG.
Harrach
B
B
Robenek
H
H
Helmhold
M
M
Walli
A K
AK
Seidel
D
D
D000345:Affinity Labels; D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D002846:Chromatography, Affinity; D004587:Electrophoresis, Agar Gel; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000302:isolation & purification / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011973:Receptors, LDL / Q000378:metabolism* / Q000648:ultrastructure; D012685:Sepharose / Q000031:analogs & derivatives; D013261:Sterols / Q000096:biosynthesis
D000345:Affinity Labels; D002788:Cholesterol Esters; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D013261:Sterols; C030675:lysine-sepharose; D012685:Sepharose