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Journal of Lipid Research, Vol. 46, 2699-2705, December 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Regulation of the selective uptake of cholesteryl esters from high density lipoproteins by sphingomyelin

Papasani V. Subbaiah¹, Laurence R. Gesquiere and Kewei Wang

Department of Medicine and Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60612

Published, JLR Papers in Press, September 14, 2005. DOI 10.1194/jlr.M500263-JLR200

¹ To whom correspondence should be addressed. e-mail: psubbaia{at}uic.edu

Although sphingomyelin (SM) is a major phospholipid in lipoproteins as well as in the membrane rafts where the scavenger receptor class B type I (SR-BI) is localized, its possible role in the selective uptake of cholesteryl ester (CE) by the SR-BI-mediated pathway is unknown. We investigated the effect of SM in lipoproteins and cell membranes on the selective uptake in three different cell lines: SR-BI-transfected CHO cells, hepatocytes (HepG2), and adrenocortical cells (Y1BS1). Incorporation of SM into recombinant high density lipoprotein (rHDL) containing labeled CE resulted in up to 50% inhibition of the selective uptake of CE in all three cell lines. This inhibition was completely reversed by treatment of rHDL with sphingomyelinase (SMase). Selective uptake from plasma HDL was activated by 22–72% after treatment of HDL with SMase. In addition, pretreatment of the cells with SMase resulted in stimulation of CE uptake from rHDL by CHO and Y1BS1, although not by HepG2. Incorporation of ceramide into rHDL resulted in up to 2-fold stimulation of CE uptake, although pretreatment of cells with egg ceramide had no significant effect.

These results show that SM and ceramide in the lipoproteins and the cell membranes regulate the SR-BI-mediated selective uptake of CE, possibly by interacting with the sterol ring or with SR-BI itself.

Abbreviations: ACTH, adrenocorticotropic hormone; apoA-I, apolipoprotein A-I; CE, cholesteryl ester; FC, free cholesterol; PC, phosphatidylcholine; rHDL, recombinant high density lipoprotein; SM, sphingomyelin; SMase, sphingomyelinase; SR-BI, scavenger receptor class B type I

Supplementary key words scavenger receptor class B type I • ceramide • sphimgomyelinase • hepatocytes • adrenocortical cells

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