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Journal of Lipid Research, Vol. 46, 36-45, January 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Interaction of cholesterol with sphingosine

Nicolas Garmy, Nadira Taïeb, Nouara Yahi and Jacques Fantini¹

Laboratoire de Biochimie et Physicochimie des Membranes Biologiques, Institut Méditerranéen de Recherche en Nutrition, Unité Mixte de Recherche-Institut National de la Recherche Agronomique 1111, Faculté des Sciences de St-Jérôme, Université Paul Cézanne, 13397 Marseille Cedex 20, France

¹ To whom correspondence should be addressed. e-mail: jacques.fantini{at}univ.u-3mrs.fr

Molecular associations between sphingomyelin and cholesterol provide a molecular basis for the colocalization of these lipids in plasma membrane microdomains (lipid rafts) and for the inhibitory effect of sphingomyelin on the intestinal absorption of cholesterol. Using surface pressure measurements at the air-water interface, we showed that sphingosine, the common sphingoid backbone of most sphingolipids, formed condensed lipid complexes with cholesterol. Structure-activity relationship studies with long-chain analogs of sphingosine, together with molecular mechanics simulations, were consistent with a specific interaction between sphingosine and the face of cholesterol. The uptake of micellar cholesterol and the effect of sphingosine on cholesterol absorption were studied with two human model intestinal epithelial cell lines, Caco-2 and HT-29-D4. Real-time PCR quantifications of the putative cholesterol transporter Niemann-Pick C1 like 1 (NPC1L1) mRNA revealed that, in these cell lines, the activity of cholesterol transport correlated with the level of NPC1L1 expression. In both cell lines, sphingosine induced a dose-dependent decrease of cholesterol absorption. Yet the effect of sphingosine was more dramatic in Caco-2 cells, which also displayed the highest expression of NPC1L1 mRNA.

Altogether, these data suggested that sphingosine interacts specifically with cholesterol and inhibits the intestinal NPC1L1-dependent transport of micellar cholesterol.

Supplementary key words sphingolipid • ceramide • sphingomyelin • Niemann-Pick C1 like 1

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