Cellular uptake of lipoprotein[a] by mouse embryonic fibroblasts via the LDL receptor and the LDL receptor-related protein.
The sites and precise mechanisms of the catabolism of the atherogenic lipoprotein[a] (Lp[a]) are unknown. It has been proposed that the low density lipoprotein receptor (LDL-R) and the low density lipoprotein receptor-related protein (LRP) are involved in the catabolism of Lp[a]. To address the question whether and to what extent the LDL-R and/or LRP are involved in the catabolism of Lp[a], we studied the cellular uptake of Lp[a] via those two receptors using mouse embryonic fibroblast (MEF) cell lines lacking either the LDL-R, the LRP, or both receptors due to disruption of the respective mouse genes. 125I-labeled LDL and 125I-labeled Lp[a] uptake by wild-type fibroblasts (MEF1) was compared with that by fibroblasts homozygous for the disrupted LRP allele (MEF2), fibroblasts with two defective alleles for the LDL-R (MEF3), and fibroblasts homozygous for defects both in the LDL-R and LRP gene (MEF4). Compared with MEF1, 125I-labeled LDL uptake by MEF2 was 77%, by MEF3 30%, and by MEF4 24% of that by MEF1. However, no significant differences in the specific 125I-labeled Lp[a] uptake by the four mouse embryonic cell lines was observed. In comparison with MEF1, the 125I-labeled Lp[a] uptake by MEF2 was 98%, by MEF3 111%, and 73% by MEF4. Approximately 50% of the total cellular uptake of 125I-labeled Lp[a] was nonspecific. In conclusion, our results suggest that Lp[a] is a poor ligand for the LDL receptor and the LRP. The data of the displacement studies, however, indicated that the nonspecific uptake of Lp[a] constitutes a major route for the cellular Lp[a] catabolism in this study.
Reblin
T
T
Medical Clinic, University Hospital Eppendorf, Hamburg, Germany.
Niemeier
A
A
Meyer
N
N
Willnow
T E
TE
Kronenberg
F
F
Dieplinger
H
H
Greten
H
H
Beisiegel
U
U
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts; D007457:Iodine Radioisotopes / Q000378:metabolism; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
D007457:Iodine Radioisotopes; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL