Effect of exogenous apo E on the cellular binding of lipoproteins.
It is well known that apolipoprotein E (apo E) has a significant role in the metabolism of plasma cholesterol through receptor-mediated endocytosis of lipoproteins containing apo B 100. We have reported that intravenous administration of apo E increases the clearance of lipoproteins containing apo B 100, resulting in reduced plasma cholesterol levels in WHHL rabbits. In the present study, we investigated the effects of exogenous apo E on lipoprotein binding to cell surface receptors. Lipoproteins were enriched in apo E by the incubation with purified apo E. Among lipoproteins enriched in apo E, VLDL and intermediate-density lipoprotein demonstrated higher binding affinity to cell surface receptor on fibroblast than respective unmodified lipoproteins. In competitive binding study, VLDL enriched by apo E (VLDL + E) completely suppressed 125I-LDL binding to human skin fibroblasts and showed the greatest binding activity among different lipoprotein classes, whereas both VLDL and LDL incompletely suppressed a binding of 125I-VLDL + E. This result indicated that apo-E-rich VLDL can bind not only to LDL receptor but to binding sites other than LDL receptors.
Mokuno
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ishibashi
S
S
Shimano
H
H
Gothoda
T
T
Takaku
F
F
Yamada
N
N
D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects*; D015243:Cholesterol, VLDL / Q000378:metabolism*; D011817:Rabbits; D011973:Receptors, LDL / Q000378:metabolism*
D001057:Apolipoproteins E; D015243:Cholesterol, VLDL; D011973:Receptors, LDL