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J. Biol. Chem., Vol. 260, Issue 5, 2694-2699, 03, 1985
TJ van Berkel, JK Kruijt, HH Spanjer, JF Nagelkerke, L Harkes and HJ Kempen
A triantennary galactose-terminated cholesterol derivative, N-
(tris(beta-D-galactopyranosyloxymethyl) methyl)-N alpha-(4-(5-cholesten- 3
beta-yloxy)succinyl)glycinamide (Tris-Gal-Chol), which dissolves easily in
water, was added to human low density lipoproteins (LDL) in varying
quantities. Upon addition to LDL, Tris-Gal-Chol was immediately
incorporated, and after intravenous injection into rats, the iodine-
labeled apolipoprotein B radioactivity was readily associated with the
liver. The incorporation of 5 or 13 micrograms of Tris-Gal-Chol into LDL
(20 micrograms of protein) stimulates the parenchymal cell association of
LDL 6- and 10-fold, respectively, at 10 min after injection. For
non-parenchymal cells, the cell association is 60- and 70-fold stimulated,
respectively. It can be calculated that non- parenchymal cells (mainly
Kupffer cells) are for 80-90% responsible for the increased,
galactose-mediated, interaction of Tris-Gal-Chol LDL with the liver. The
increased interaction of LDL with the cells upon Tris-Gal-Chol
incorporation is followed by degradation of the apolipoprotein B in the
lysosomes. Incorporation of Tris-Gal-Chol into unilamellar liposomes (10
mol %) leads to an increased cell association of the enclosed [3H]inulin to
parenchymal cells (1.4-fold) and non- parenchymal cells (11.8-fold). It is
concluded that Tris-Gal-Chol incorporation into LDL leads to a markedly
increased catabolism of LDL by the liver which might be used for lowering
serum LDL levels. The possibility of increasing the interaction of LDL or
liposomes with specific liver cell types by Tris-Gal-Chol might also have
an application for targeting drugs or other compounds of interest to these
cells.
The effect of a water-soluble tris-galactoside-terminated cholesterol derivative on the fate of low density lipoproteins and liposomes
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