title: Cholesteryl esters from oxidized low-density lipoproteins are in vivo rapidly hydrolyzed in rat Kupffer cells and transported to liver parenchymal cells and bile.
abstract: Human low-density lipoprotein was labeled in its cholesteryl ester moiety with [3H]cholesteryl oleate or [3H]cholesteryl oleoyl ether and oxidized by exposure to 10 mumol/L of cupric sulfate. The in vivo metabolism of cholesteryl esters of oxidized low-density lipoprotein was determined after injection into rats. When oxidized low-density lipoprotein was labeled with [3H]cholesteryl oleoyl ether, a nonhydrolyzable analog of cholesteryl oleate, Kupffer cells contributed to 55.1% +/- 4.1% of the total liver uptake 10 min after injection. When [3H]cholesteryl oleate-labeled oxidized low-density lipoprotein was injected, the radiolabeled cholesterol esters were nearly completely hydrolyzed within 1 hr of injection. Within this time, the Kupffer cell-associated radioactivity declined to 32% of the maximal uptake value. In serum, the highest specific resecreted [3H]cholesteryl (esters) were associated with the serum high-density lipoprotein fraction, suggesting a role for high-density lipoprotein as an in vivo cholesterol acceptor. The kinetics of biliary secretion were studied in rats equipped with catheters in the bile duct, duodenum and heart. One hour after injection of [3H]cholesteryl oleate-labeled oxidized low-density lipoprotein, 4.15% +/- 0.67% of the injected dose was secreted in the bile, mainly as bile acids. Six hours after injection, this value was 19.2% +/- 1.2%. These values are three times higher than those for injected [3H]cholesteryl oleate-labeled acetylated low-density lipoprotein, which is initially mainly taken up by liver endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Biopharmaceutics, Sylvius Laboratory, University of Leiden, The Netherlands.
authors.forename: M N
authors.initials: MN
authors.lastname: Pieters
authors.forename: S
authors.initials: S
authors.lastname: Esbach
authors.forename: D
authors.initials: D
authors.lastname: Schouten
authors.forename: A
authors.initials: A
authors.lastname: Brouwer
authors.forename: D L
authors.initials: DL
authors.lastname: Knook
authors.forename: T J
authors.initials: TJ
authors.lastname: Van Berkel
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D002788:Cholesterol Esters / Q000493:pharmacokinetics*; D006801:Humans; D006868:Hydrolysis; D007728:Kupffer Cells / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002788:Cholesterol Esters; D008077:Lipoproteins, LDL