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J. Biol. Chem., Vol. 281, Issue 50, 38159-38171, December 15, 2006

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A Chinese Hamster Ovarian Cell Line Imports Cholesterol by High Density Lipoprotein Degradation^*

Tamara A. Pagler, Solmaz Golsabahi, Marlon Doringer, Sebastian Rhode, Gerhard J. Schütz, Margit Pavelka^¶, Christian Wadsack^||, Martin Gauster^||, Alfred Lohninger, Hildegard Laggner, Wolfgang Strobl, and Herbert Stangl¹

From the Center for Physiology and Pathophysiology, Institute of Medical Chemistry, Medical University of Vienna, Währingerstrasse 10, A-1090 Vienna, Austria, Institute of Biophysics, Johannes-Kepler-University Linz, Altenbergerstrasse 69, A-4040 Linz, Austria, ^¶Center for Anatomy and Cell Biology, Department of Cell Biology and Ultrastructure Research, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria, and the ^||Clinic of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria

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.

Received for publication, April 7, 2006 , and in revised form, October 12, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by Austrian Science Foundation Grants J1488-GEN and P16362-B07 and OENB Fond Project 8198. To whom correspondence should be addressed: Center for Physiology and Pathophysiology, Institute of Medical Chemistry, Medical University of Vienna, Währingerstrasse 10, A-1090 Vienna, Austria. Tel.: 43-1-4277-60823; Fax: 43-1-4277-60881; E-mail: Herbert.Stangl{at}meduniwien.ac.at.

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