Interaction of Lp(a) and of apo(a) with liver cells.
Lipoprotein(a) (Lp[a]) is a lipoprotein of high atherogenicity with unknown function. Although it binds in vitro to the low-density lipoprotein (LDL) receptor, it is not clear whether this mechanism also operates in vivo. We studied the interaction of Lp(a) and of apoprotein(a) (apo[a]) with hepatoma cells (HepG2 and Hep3B) with the following results. (1) HepG2 cells exhibited saturable high-affinity binding of LDLs, whereas the majority of Lp(a) binding was of low affinity and nonsaturable. Preincubation of HepG2 cells with LDL markedly reduced cholesterol biosynthesis, but Lp(a) had a much lower effect. (2) When HepG2 cells were preincubated for 48 to 72 hours with Lp(a) or apo(a), 125I-LDL binding was increased by a factor of > 2. During this time, up to approximately 1 microgram of apo(a) per 1 milligram cell protein was found to be cell associated in an undegraded form. Monoclonal antibodies against the LDL receptor did not prevent the increase in LDL binding stimulated by apo(a). (3) Coincubation with LDL caused a significant increase of Lp(a) degradation by HepG2 cells that was probably caused by an increase of Lp(a) uptake in a "hitchhiking"-like process.
Kostner
G M
GM
Institute of Medical Biochemistry, University of Graz, Austria.
D001054:Apolipoproteins A / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis; D008076:Cholesterol, HDL / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D011485:Protein Binding; D011973:Receptors, LDL / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D008148:Lovastatin