Journal of Lipid Research, Vol 18, 451-458, Copyright © 1977 by Lipid Research, Inc.
A comparative study of surface binding of human low density and high density lipoproteins to human fibroblasts: regulation by sterols and susceptibility to proteolytic digestion
T Koschinsky, TE Carew and D Steinberg
Binding of 125I-low density lipoprotein (LDL) and 125I-high density
lipoprotein (HDL) was determined in cultured human fibroblasts from a
normal subject and two subjects with homozygous familial
hypercholesterolemia (HFH). Binding was assayed at 0 degree C to minimize
the internalization of labeled lipoproteins. The binding of LDL and of HDL
were compared following interventions reported to affect LDL binding in
normal fibroblast. LDL binding to normal cells increased two to three fold
24 hours after transfer from medium containing whole fetal calf serum to
medium containing lipoprotein-deficient fetal calf serum. This increase was
completely blocked in the presence of cycloheximide (200 microgram/ml) or
7-ketocholesterol (2.5 microgram/ml). This increased capacity of normal
fibroblasts to bind LDL could be reduced 70-80% by a subsequent 18-hour
incubation with cholesterol (50 microgram/ml) or 7-ketocholesterol (2.5
microgram/ml). In contrast, no significant change in HDL binding to normal
fibroblasts was observed after any of these interventions. HFH cells to
show any significant change in either LDL binding or HDL binding following
these interventions. These results suggest that HDL binding sites on normal
fibroblasts are for the most part distinct from LDL binding sites. They
also support the conclusion that LDL binding sites on HFH cells are for the
most part qualitatively different from those on normal cells.
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