title: A Chinese hamster ovarian cell line imports cholesterol by high density lipoprotein degradation.
abstract: Plasma high density lipoprotein (HDL) is inversely associated with the development of atherosclerosis. HDL exerts its atheroprotective role through involvement in reverse cholesterol transport in which HDL is loaded with cholesterol at the periphery and transports its lipid load back to the liver for disposal. In this pathway, HDL is not completely dismantled but only transfers its lipids to the cell. Here we present evidence that a Chinese hamster ovarian cell line (CHO7) adapted to grow in lipoprotein-deficient media degrades HDL and concomitantly internalizes HDL-derived cholesterol. Delivery of HDL cholesterol to the cell was demonstrated by a down-regulation of cholesterol biosynthesis, an increase in total cellular cholesterol content and by stimulation of cholesterol esterification after HDL treatment. This HDL degradation pathway is distinct from the low density lipoprotein (LDL) receptor pathway but also degrades LDL. 25-Hydroxycholesterol, a potent inhibitor of the LDL receptor pathway, down-regulated LDL degradation in CHO7 cells only in part and did not down-regulate HDL degradation. Dextran sulfate released HDL bound to the cell surface of CHO7 cells, and heparin treatment released protein(s) contributing to HDL degradation. The involvement of heparan sulfate proteoglycans and lipases in this HDL degradation was further tested by two inhibitors genistein and tetrahydrolipstatin. Both blocked HDL degradation significantly. Thus, we demonstrate that CHO7 cells degrade HDL and LDL to supply themselves with cholesterol via a novel degradation pathway. Interestingly, HDL degradation with similar properties was also observed in a human placental cell line.
authors.affiliation: Center for Physiology and Pathophysiology, Institute of Medical Chemistry, Medical University of Vienna, Währingerstrasse 10, A-1090 Vienna, Austria.
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Pagler
authors.forename: Solmaz
authors.initials: S
authors.lastname: Golsabahi
authors.forename: Marlon
authors.initials: M
authors.lastname: Doringer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rhode
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Schütz
authors.forename: Margit
authors.initials: M
authors.lastname: Pavelka
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
authors.forename: Martin
authors.initials: M
authors.lastname: Gauster
authors.forename: Alfred
authors.initials: A
authors.lastname: Lohninger
authors.forename: Hildegard
authors.initials: H
authors.lastname: Laggner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Strobl
authors.forename: Herbert
authors.initials: H
authors.lastname: Stangl
mesh_terms: D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004951:Esterification; D005260:Female; D006868:Hydrolysis; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D008075:Lipoproteins, HDL; D002784:Cholesterol