Intracellular cholesterol transport

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      Recent data on the roles of vesicle- and ‘raft‘-mediated pathways in intracellular free cholesterol (FC) transport are reviewed. Cholesterol internalized from plasma lipoproteins is transferred via endocytic vesicles to the trans-Golgi network (TGN), consistent with prior data indicating a key role for this organelle in protein and lipid sorting and transport. Newly synthesized and lipoprotein-derived FC are returned to the cell surface by a common raft-dependent pathway. Intracellular FC transport promotes the delivery of GPI-anchored proteins to the cell surface; it is also an additional mechanism to regulate cell FC content. Many peripheral cells express caveolin, an FC-binding protein localized to plasma membrane caveolae. FC delivery to cell surface caveolae is accelerated by caveolin. Caveolar FC becomes targeted to small, lipid-poor (prebeta-) high density lipoprotein particles. Caveolin may protect quiescent cells, regulating FC efflux more efficiently in response to changing medium lipoprotein concentrations. Overall, these recent findings suggest that cell FC content can be regulated at the levels of both influx and efflux, and indicate key roles for the TGN and in cells expressing caveolin, cell-surface caveolae.

      REFERENCES

        • Schroeder F.
        • Nemecz G.
        Transmembrane cholesterol distribution. In Advances in Cholesterol Research.
        in: Esfahani M. Swaney j. Telford Press, Caldwell, NJ1990: 47-87
        • Schroeder F.
        • Jefferson J.R.
        • Kier A.B.
        • Knittel J.
        • Scallen T.J.
        • Wood W.G.
        • Hapala I.
        Membrane cholesterol dynamics-cholesterol domains and kinetic pools.
        Proc. Soc. Exp. Biol. Med. 1991; 196: 235-252
        • Yeagle P.L.
        Cholesterol and the cell membrane.
        in: Yeagle P.C. In Biology of Cholesterol. CRC Press,, Boca Raton, FL.1988: 121-145
        • Orci L.
        • Montesano R.
        • Meda P.
        • Malaisse-Lagae F.
        • Brown D.
        • Perrelet A.
        • Vasalli P.
        Heterogeneous distribution of filipin-cholesterol complexes across the cisternae of the Golgi apparatus.
        Proc. Natl. Acad. Sci. USA. 1981; 78: 293-297
        • Penman S.
        Rethinking cell structure.
        Proc. Natl. Acad. Sci. USA. 1995; 92: 5251-5257
        • Goldstein J.L.
        • Brown M.S.
        • Anderson R.G.W.
        • Russell D.W.
        • Schneider W.J.
        Receptor-mediated endocytosis. Annu. Rev.
        Cell Biol. 1985; 1: 1-39
        • Fielding C.J.
        • Fielding P.E.
        Role of an N-ethylmaleimide-sensitive factor in the selective cellular uptake of low density lipoprotein free cholesterol.
        Biochemistry. 1995; 34: 14237-14244
        • Acton S.
        • Rigotti A.
        • Landschultz K.T.
        • Xu S.
        • Hobbs H.H.
        • Krieger M.
        Identification of scavenger receptor SR-B1 as a high density lipoprotein receptor.
        Science. 1996; 271: 518-520
        • Reaven E.
        • Tsai L.
        • Azhar S.
        Cholesterol uptake by the selective pathway of ovarian granulosa cells: early intracellular events.
        J. Lipid Res. 1995; 36: 1602-1617
        • Warner G.J.
        • Stoudt G.
        • Bamberger M.
        • Johnson W.J.
        • Rothblat G.H.
        Cell toxicity induced by inhibition of acyl CoAxholesterol acyltransferase and accumulation of unesterified cholesterol.
        J. Biol. Chem. 1995; 270: 5772-5778
        • Liscum L.
        • K W.
        Intracellular cholesterol transport and compartmentation.
        J. Biol. Chem. 1995; 270: 15443-15446
        • Lange Y.
        • Steck T.L.
        The role of intracellular cholesterol transport in cholesterol homeostasis.
        Trends CeU. Biol. 1996; 6: 205-208
        • Steinman R.M.
        • Mellman I.S.
        • Muller W.A.
        • Cohn Z.A.
        Endocytosis and the recycling of plasma membrane.
        J. Cell Biol. 1983; 96: 1-27
        • Cupers P.
        • Veithen A.
        • Kiss A.
        • Baudhuin P.
        • Courtoy P.J.
        Clathrin polymerization is not required for bulk-phase endocytosis in rat fetal fibroblasts.
        J. Cell Biol. 1994; 127: 725-735
        • Pierce B.M.F.
        Clathrin: a unique protein associated with intracellular transfer of membrane by coated pits.
        Proc. Natl. Acad. Sci. USA. 1976; 73: 1255-1259
        • Santini F.
        • Keen j.H.
        Endocytosis of activated receptors and clathrin coated pit formation: deciphering the chick or egg relationship.
        J. Cell Biol. 1996; 132: 1025-1036
        • Hinshaw J.E.
        • Schmit S.L.
        Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding.
        Nature. 1995; 374: 190-192
        • Holstein S.E.H.
        • Ungewickell H.
        • Ungewickell E.
        Mechanism of clathrin basket dissociation: separate functions of protein domains of the DnaJ homologue auxilin.
        J. CeU Biol. 1996; 135: 925-937
        • Ungewickell E.
        • Ungewickell H.
        • Holstein S.E.H.
        • Lindner R.
        • Prasad K.
        • Barouch W.
        • Martin B.
        • Greene L.E.
        • Eisenberg E.
        Role of auxilin in uncoating clathrin-coated vesicles.
        Nature. 1995; 378: 632-635
        • Wang L.H.
        • Sudhof T.C.
        • Anderson R.G.W.
        The appendage domain of alpha-adaptin is a high affinity binding site for dynamin.
        J. Biol. Chem. 1995; 270: 79-83
        • Brodsky F.M.
        Living with clathrin: its role in intracellular membrane traffic.
        Science. 1988; 242: 1396-1401
        • Simionescu N.
        • Lupu F.
        • Simionescu M.
        Rings of membrane sterols surround the openings of vesicles and fenestrae, in capillary endothelium.
        J. Cell Biol. 1983; 97: 1592-1600
        • Mineo C.
        • Anderson R.G.W.
        A vacuolar-type proton ATPase mediates acidification of plasmalemmal vesicles during potocytosis.
        Exp. Cell Res. 1996; 224: 237-242
        • Parton R.G.
        • Joggerst B.
        • Simons K.
        Regulated internalization of caveolae.
        j. Cell Biol. 1994; 127: 1199-1215
        • Li S.
        • Song G.S.
        • Lisanti M.P.
        Expression and characterization of recombinant caveolin. Purification by polyhistidine tagging and cholesterol-dependent incorporation into defined lipid membranes.
        J. Biol. Chem. 1996; 271: 568-573
        • Murata M.
        • Peranen J.
        • Schreiner R.
        • Wieland F.
        • Kurzchalia T.V.
        • Simons K.
        VIP21Jcaveolin is a cholesterol-binding protein.
        Proc. Natl. Acad. Sci. USA. 1995; 92: 10339-10343
        • Fra A.M.
        • Williamson E.
        • Simons K.
        • Parton R.G.
        De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin.
        Proc. Natl. Acad. Sci. USA. 1995; 92: 8655-8659
        • Scherer P.E.
        • Tang Z.
        • Chun M.
        • Sargiacomo M.
        • Lodish H.F.
        • Lisanti M.P.
        Caveolin isoforms differ in their N-terminal protein sequence and subcellular distribution.
        j. Biol. Chem. 1995; 270: 16395-16401
        • Dupree P.
        • Parton R.G.
        • Raposo G.
        • Kurzchalia T.V.
        • Simons K.
        Caveolae and sorting in the trans-Golgi network of epithelial cells.
        EMBOJ. 1993; 12: 1597-1605
        • Song K.S.
        • Li S.
        • Okamoto T.
        • Quilliam L.A.
        • Sargiacomo M.
        • Lisanti M.P.
        Copurification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains.
        J. Biol. Chem. 1996; 271: 9690-9697
        • Dietzen D.J.
        • Hastings W.R.
        • Lublin D.M.
        Caveolin is palmitoylated on multiple cysteine residues. Palmitoyladon is not necessary for localization of caveolin to caveolae.
        J. Biol. Chem. 1995; 270: 6838-6842
        • Schnitzer J.E.
        • Liu J.
        • Oh P.
        Endothelial caveolae have the molecular transport machinery for vesicle budding, docking and fusion including VAMP, NSF, SNAP, annexins and GTPases.
        J. Biol. Chem. 1995; 270: 14399-14404
        • Schnitzer J.E.
        • McIntosh D.P.
        • Dvorak A.M.
        • Liu J.
        • Oh P.
        Separation of caveolae from associated microdomains of GPI-anchored proteins.
        Science. 1995; 269: 1435-1439
        • Mayor S.
        • Rothberg K.G.
        • Maxwell F.R.
        Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking.
        Science. 1994; 264: 1948-1951
        • Ilangumaran S.
        • Robinson P.J.
        • Hoessli D.C.
        Transfer of exogeneous glycosyl-phosphatidylisolitol (GPI)-linked molecules to plasma membranes.
        Trends Cell Biol. 1996; 6: 163-167
        • Yen C.F.
        • Kalunta C.I.
        • Chen F-S.
        • Kaptein J.S.
        • Lin C-K. E.
        • Lad P.M.
        Regulation of low density lipoprotein receptors and assessment of their functional role in Burkitt's lymphoma cells.
        Biochim. Biophys. Acta. 1995; 1257: 47-57
        • Koleske A.J.
        • Baltimore D.
        • Lisanti M.P.
        Reduction of caveolin and caveolae in oncogenically transformed cells.
        Proc. Natl. Acad. Sci. USA. 1995; 92: 1381-1385
        • Fra A.M.
        • Williamson E.
        • Simons K.
        • Parton R.G.
        Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae.
        J. Biol. Chem. 1994; 269: 30745-30748
        • Bohuslav J.
        • Cinek T.
        • Horejsi V.
        Large, detergent resistant complexes containing murine antigens Thy-1 and Ly-6 and protein tyrosine kinase p56lck.
        Eur. J. Immunol. 1993; 23: 825-831
        • Reichl D.
        • Forte T.M.
        • Hong J-L.
        • Rudra D.N.
        • Pflug J.
        Human lymphoedema fluid lipoproteins: particle size, cholesterol, and apolipoprotein distributions, and electron microscopic structure.
        J. Lipid Res. 1985; 26: 1399-1411
        • Fielding P.E.
        • Fielding C.J.
        Intracellular transport of low density lipoprotein-derived free cholesterol begins at clathrin-coated pits and terminates at cell surface caveolae.
        Biochemistry. 1996; 35: 14932-14938
        • Koval M.
        • Pagano R.E.
        Lipid recycling between the plasma membrane and intracellular compartments: transport and metabolism of fluorescent sphingomyelin analogues in cultured fibroblasts.
        J. Cell Biol. 1989; 108: 2169-2181
        • Koval M.
        • Pagano R.E.
        Sorting of an internalized plasma membrane lipid between recycling and de-gradative pathways in normal and Niemann-Pick Type A fibroblasts.
        J Cell Biol. 1990; 111: 429-442
        • Fukuda S.A.
        • Horiuchi S.
        • Tomita K.
        • Murakami M.
        • Morino Y.
        • Takahashi K.
        Acetylated low density lipoprotein is endocytosed through coated pits by rat peritoneal macrophages.
        Virchows Archiv. (B). 1986; 52: 1-13
        • Gwynne J.T.
        • Hess B.
        The role of high density lipoproteins in rat adrenal cholesterol metabolism and steroidogenesis.
        J. Biol. Chem. 1980; 255:: 10875-10883
        • Pittman R.C.
        • Kmecht T.P.
        • Rosenbaum M.S.
        • Taylor C.A.
        A nomendocytotic mechanism for the selective uptake of high density lipoprotein-associated cholesteryl esters.
        J. Biol. Chem. 1987; 262:: 2443-2445
        • Sparrow C.P.
        • Pittman R.C.
        Cholesteryl esters selectively taken up from high density lipoproteins are 'hydrolyzed extralysosomally.
        Biochim. Biophys. Acta. 1990; 1043: 203-210
        • Medicherla S.
        • Azhar S.
        • Cooper A.
        • Reaven E.
        Regulation of cholesterol responsive genes in ovary cells'impact of cholesterol delivery systems.
        Biochemistry. 1996; 35: 6243-6250
        • Brasaemle D.L.
        • Attie A.D.
        Rapid intracellular transport of LDL-derived cholesterol to the plasma membrane in cultured fibroblasts.
        J. Lipid Res. 1990; 31: 103-112
        • Spillane D.M.
        • Regan J.W.
        • Kennedy N.J.
        • Schneider D.L.
        • Chang T-Y.
        Translocation of both lysosomal LDLrderived cholesterol and plasma membrane cholesterol to the endoplasmic reticulum for esterifica-tion may require common factors involved in cholesterol egress from the acidic compartments.
        Biochim. Biophys. Acta. 1995; 1254: 283-294
        • Lange Y.
        • Steck T.L.
        Modulation by amphiphiles Cholesterol homeostasis.
        J. Biol. Chem. 1994; 269: 29371-29374
        • Mazzone T.
        • Krishna M.
        • Lange Y.
        Progesterone blocks intracellular location of free cholesterol derived from cholesteryl ester in macrophages.
        J. Lipid Res. 1995; 36: 544-551
        • Underwood, K W.
        • Andemariam B.
        • McWilliams G.L.
        • Liscum L.
        Quantitative analysis of hydrophobic amine inhibition of intracellular cholesterol transport.
        J. Lipid Res. 1996; 37: 1556-1568
        • Sato Y.
        • Nishikawa K.
        • Aikawa K.
        • Mimura K.
        • Mura-kami-Murofushi K.
        • Arai H.
        • Inoue K.
        Side-chain structure is critical for the transport of sterols from lysosomes to cytoplasm.
        Biochim. Biophys. Acta. 1995; 1257: 38-46
        • Coxey R.A.
        • Pentchev P.G.
        • Campbell G.
        • Blanchette-Mackie E.J.
        Differential accumulation of cholesterol in Golgi compartments of normal and Nie-man n-Pick type C fibroblasts incubated with LDL: a cyto*-chemical freeze-fracture study.
        J. Lipid Res. 1993; 34: 1165-1176
        • Griffiths G.
        • Simons K.
        The trans Golgi nee-work: sorting at the exit site of the Golgi complex.
        Science. 1986; 234: 438-443
        • Bretscher M.S.
        • Munro S.
        Cholesterol and the Golgi apparatus.
        Science. 1903; 261: 1280-12811
        • Pfeffer S.R.
        Targeting of proteins to the lysosome.
        Curr. Top. Microbiol. Immunol. 1991; 170: 43-65
        • Rothman J.E.
        • Wieland F.T.
        Protein sorting by transport vesicles.
        Science. 1996; 272: 227-234
        • Reinhart M.P.
        Intracellular sterol trafficking.
        Ex-perientia. 1990; 46: 599-611
        • Simons K.
        • Ikonen E.
        Functional rafts in cell membranes.
        Nature. 1997; 387: 569-572
        • Hanada K
        • Nishijima M.
        • Akamatsu y
        • Pagano R.E.
        Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase, a glycosyl-phosphatidylinositol-anchored protein, in mammalian membranes.
        J. Biol. Chem. 1995; 270: 6254-6260
        • Yoshimori T.
        • Kellter P.
        • Roth M.G.
        • Simons K.
        Different biosynthetic transport routes to the plasma membrane in BHK and CHO cells.
        J. Cell Biol. 1996; 133: 247-256
        • Mayer A.
        • Ivanov I.E.
        • Gravotta DY
        • Adesnik M.
        • Sabatini D.D.
        Cell-free reconstitution of the transport of viral glycoproteins from the TGN to the basolat-eral membrane of MDCK cells.
        J. Cell Sci. 1996; 109: 1667-1676
        • Ikonen E.
        • Tagaya M.
        • Ullrich O.
        • Montecucco C.
        • Simons K.
        Different requirements for NSF, SNAP and Rab proteins in apical and basolateral transport in MDCK cells.
        Cell. 1995; 81: 571-580
        • Zacchetti D.
        • Peranen J.
        • Murata M.
        • Fiedler K.
        • Simons K.
        VIP17JMAL, a proteolipid in apical transport vesicles.
        FEBS Lett. 1995; 377: 465-469
        • Arreaza G.
        • Brown D.A.
        Sorting and intracellular trafficking of a glycosylphosphatidylinositol-anchored protein and two hybrid transmembrane proteins with the same ectodomain in Madin-Darby canine kidney epithelial cells.
        J Biol. Chem. 1995; 270: 23641-23647
        • Kurzchalia T.V.
        • Dupree P.
        • Parton R.G.
        • Kellner R.
        • Virta H.
        • Lehnert M.
        • Simons K
        VIP21, a 21 kJDa membrane protein is an integral component of tems-Golgi network-derived transport vehicles.
        J. Cell Biol. 1992; 118: 1003-1014
        • Conrad P.A.
        • Smart E.J.
        • Ying Y.S.
        • Anderson R.G.W.
        • Bloom G.S.
        Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule-dependent and microtubule-independent steps.
        J. CellBmt. 1995; 131: 1421-1433
        • van Meer G.
        • van't Hof W.
        Epithelial sphin-golipid sorting is insensitive to reorganization of the Golgi by nocodazole but is abolished by monensin in MDCK cells and by brefeldin in CaCo-2 cells.
        J. Cell Sci. 1993; 104: 833-842
        • Alonso F.V.
        • Compans R.W.
        Differential effect of monensin on enveloped viruses that form at distinct plasma membrane domains.
        J Cell Biol. 1981; 89: 700705
        • Chege N.W.
        • Pfeffer S.R.
        Compartmenta-tion of the Golgi complex: brefeldin-A distinguishes irajw-Golgi cistemae from the rrms-Golgi network.
        J. Cell Biol. 1990; 111: 893-899
        • Fielding P.E.
        • Fielding C.J.
        Plasma membrane caveolae mediate the efflux of cellular free cholesterol.
        Biochemistry. 1995; 34: 14288-14292
        • Hannan L.A.
        • Edidin M.
        Traffic, polarity and detergent solubility of a glycosylphosphatidylinositol-anchored protein after LDL deprivation of MDCK cells.
        J. Cell Biol. 1996; 133: 1265-1276
        • Mitchell D.M.
        • Kochevar D.T.
        The effect of sterols and brefeldin A on protein degradation in UT-1 cells.
        Exp. Cett Res. 1995; 216: 135-142
        • Smart E.J.
        • Ying Y-S.
        • Donzell W.C.
        • Anderson R.G.W.
        A role for caveolin in transport of cholesterol from endoplasmic reticulum to plasma membrane.
        J. Biol. Chem. 1996; 271: 29427-29435
        • Mendez, A J.
        Monensin and brefeldin A inhibit high density lipoprotein-mediated cholesterol efflux from cholesterol-enriched cells. Implications for intracellular cholesterol transport.
        J. Biol. Chem. 1995; 270: 58915900
        • Mendez A.J.
        • Uint L.
        Apolipoprotein-medi-ated cellular cholesterol and phospholipid efflux depends on a functional Golgi apparatus.
        J. Lipid Res. 1996; 37: 2510-2524
        • Fielding C.J.
        • Bist A.
        • Fielding P.E.
        Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers.
        Proc. Natl. Acad. Sci. USA. 1997; 94: 3753-3758
        • Castro G.R.
        • Fielding C.J.
        Early incorporation of cell-derived cholesterol into preβ-migrating high density lipoprotein.
        Biochemistry. 1988; 27: 25-29
        • Chang T.Y.
        • Chang C.Y.
        • Cheng D.
        Acyl-coenzyme Axholesterol acyltransferase.
        Annu. Rev. Bio-chem. 1997; 66: 237-265
        • Brown M.S.
        • Goldstein j.L.
        Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis.
        Annu. Rev. Biochem. 1983; 52: 223-261
        • Klansek J.J.
        • Warner G.J.
        • Johnson W.J.
        • Glick j.M.
        Compartmental isolation of cholesterol participating in the cytoplasmic cholesteryl ester cycle in Chinese hamster ovary 25-RA cells.
        J. Biol. Chem. 1996; 271: 4923-4929
        • Cheng D.
        • Chang C.C.Y.
        • Qu X.M.
        • Chang T-Y.
        Activation of acyl CoAxholesterol acyltransferase by cholesterol or by oxysterol in a cell-free system.
        J. Biol. Chem. 1995; 270: 685-695
        • Matsuda H.
        • Hakamata H.
        • Miyazaki A.
        • Sakai M.
        • Chang C.C.Y.
        • Chang T.Y.
        • Kobori S.
        • Shichiri M.
        • Horiuchi S.
        Activation of acyl CoAxholesterol acyltransferase by cholesterol is not due to altered mRNA levels in HepG2 cells.
        Biochim. Biophys. Acta. 1996; 1301: 76-84
        • Neufeld E.B.
        • Cooney A.M.
        • Pitha J.
        • Dawidowicz E.A.
        • Dwyer N.K.
        • Pentchev P.G.
        • Blanchette-Mackie E.J.
        Intracellular trafficking of cholesterol monitored with a cyclodextrin.
        J. Biol. Chem. 1996; 271: 21604-21613
        • Lange Y.
        • Duan H.
        • Mazzone T.
        Cholesterol homeostasis is modulated by amphiphiles at transcriptional and posttranscriptional loci.
        J. Lipid Res. 1996; 37: 534539
        • Hua X.
        • Yokoyama C.
        • Wu J.
        • Briggs M.R.
        • Brown M.S.
        • Goldstein j.L.
        SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element.
        Proc. Natl. Acad. Sci.USA. 1993; 90: 11603-11607
        • Wang X.
        • Briggs M.R.
        • Hua X.
        • Yokoyama C.
        • Goldstein J.L.
        • Brown M.S.
        Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter.
        Purification and characterization.J. Biol. Chem. 1993; 268: 14497-14504
        • Vallett S.M.
        • Sanchez H.B.
        • Rosenfeld J.M.
        • Osborne T.F.
        A direct role for sterol regulatory element binding protein in activadon of 3-hydroxy-3-meth-ylglutaryl coenzyme A reductase gene.
        J. Biol. Chem. 1996; 271: 12247-12253
        • Ericsson J.
        • Jackson S.M.
        • Lee B.C.
        • Edwards P.A.
        Sterol regulatory element binding protein binds to a cis element in the promoter of the farnesyl diphosphate synthase gene.
        Proc. Natl. Acad. Sci. USA. 1996; 93: 945950
        • Rothblat G.H.
        • Mahlberg F.H.
        • Johnson W.J.
        • Phillips M.C.
        Apolipoproteins, membrane cholesterol domains, and the regulation of cholesterol efflux.
        J Lipid Res. 1992; 33: 1091-1097
        • Fielding C.J.
        • Fielding P.E.
        Molecular physiology of reverse cholesterol transport.
        J. Lipid Res. 1995; 36: 211-228
        • Oram J.F.
        • Yokoyama S S.
        Apolipoprotein-mediated removal of cellular cholesterol and phospholipids.
        J. Lipid Res. 1996; 37: 2473-2491
        • Francis G.A.
        • Knopp R.H.
        • Oram j.F.
        Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease.
        J. Clin. Invest. 1995; 96: 78-87
        • Hsu H-Y.
        • Nicholson A.C.
        • Pomerantz K.B.
        • Kaner R.J.
        • Hajjar D.P.
        Altered cholesterol trafficking in herpes-virus-infected arterial cells. Evidence for viral protein-kinase-mediated cholesterol accumulation.
        J. Biol. Chem. 1995; 270: 19630-19637
        • Li Q.
        • Yokoyama S.
        Independent regulation of cholesterol incorporation into free apolipoprotein-mediated cellular lipid efflux in rat vascular smooth muscle cells.
        J Biol. Chem. 1995; 270: 26216-26223
        • Yancey P.G.
        • Bielicki J.K.
        • Johnson W.J.
        • Lund-Katz S.
        • Palgunachari M.N.
        • Anantharamaiah G.M.
        • Segrest J.P.
        • Phillips M.C.
        • Rothblat G.H.
        Efflux of cellular cholesterol and phospholipid to lipid-free apolipoproteins and class A amphipathic peptides.
        Biochemistry. 1995; 34: 7955-7965
        • Saito H.
        • Miyako Y.
        • Handa T.
        • Miyajima T.
        Effect of cholesterol on apolipoprotein A-I binding to lipid bilayers and emulsions.
        J. Lipid Res. 1997; 38: 287-294
        • McKnight G.L.
        • Reasoner J.
        • Gilbert T.
        • Sund-quist K.O.
        • Hokland B.M.
        • McKernan P.A.
        • Champagne J.
        • Johnson C.J.
        • Bailey M.C.
        • Holly R.
        • O'Hara P.J.
        • Oram J.F.
        Cloning and expression of a cellular high density lipoprotein-binding protein that is up-regulated by cholesterol loading of cells.
        Biol. Chem. 1992; 267: 12131-12141
        • Plenz G.
        • Kugler S.
        • Schnittger S.
        • Rieder H.
        • Fo natsch C.
        • Muller P.K.
        The human vigilin gene: identification, chromosomal localization and expression pattern.
        Hum. Genet. 1994; 93: 575-582
        • Kawano M.
        • Miida T.
        • Fielding C.J.
        • Fielding P.E.
        Quantitation of pre(3-HDL dependent and nonspecific components of the total efflux of cellular cholesterol and phospholipid.
        Biochemistry. 1993; 32: 5025-5028
        • Deckert M.
        • Ticchioni M.
        • Bernard A.
        Endocytosis of GPI-anchored proteins in human lymphocytes: role of glycolipid-based domains, actin cytoskeleton, and protein kinases.
        J. Cell Biol. 1996; 133: 791-799
        • Kok J.W.
        • Eskelinen S.
        • Hoekstra K.
        • Hoekstra D.
        Salvage of glucosylceramide by recycling after internalization along the pathway of receptor-mediated endocytosis.
        Proc. Natl. Acad. Sci. USA. 1989; 86: 98969900
        • Kellie S.
        • Patel B.
        • Pierce E.J.
        • Critchley D.R.
        Capping of cholera toxin-ganglioside GM, complexes on mouse lymphocytes is accompanied by co-capping of a-actinin.
        J Cell Biol. 1983; 97: 447-454
        • Kesav S.
        • McLaughlin J.
        • Scallen T.J.
        Partici-padon of sterol carrier protein 2 in cholesterol metabolism.
        Biochem. Soc. Trans. 1992; 20: 818-824
        • Thompson S.L.
        • Burrows R.
        • Laub R.J.
        • Kri-sans S.K.
        Cholesterol synthesis in rat liver peroxisomes. Conversion of mevalonic acid to cholesterol..
        J. Biol. Chem. 1987; 262: 17420-17425
        • Ohba T.
        • Rennert H.
        • Pfeifer S.M.
        • He Z.
        • Yamamoto R.
        • Holt J.A.
        • Billheimer J.T.
        • Strauss J.F.
        The structure of the human sterol carrier protein XJsterol carrier protein 2 gene (SCP2).
        Genomics. 1994; 24: 370-374
        • Frolov A.
        • Woodford J.K.
        • Murphy E.J.
        • Billheimer J.T.
        • Schroeder F.
        Spontaneous and protein-mediated sterol transfer between intracellular membranes.
        J. Biol. Chem. 1996; 271: 16075-16083
        • Baum C.L.
        • Reschly E.J.
        • Gayen A.K.
        • Groh M.E.
        • Schadick K.
        Sterol carrier protein-2 overexpression enhances sterol cycling and inhibits cholesterol ester synthesis and high density lipoprotein cholesterol secretion.
        J Biol. Chem. 1997; 272: 6490-6498
        • Moncecchi D.
        • Murphy E.J.
        • Prows D.R.
        • Schroeder F.
        Sterol carrier protein-2 expression in mouse L-cell fibroblasts alters cholesterol uptake.
        Bio-chim. Biophys. Acta. 1996; 1302: 110-116
        • Johnson W.J.
        • Reinhart M.P.
        Lack of requirement for sterol carrier protein-2 in the intracellular trafficking of lysosomal cholesterol.
        J Lipid Res. 1994; 35: 563573
        • Puglielli L.
        • Rigotti A.
        • Greco A.V.
        • Santos M.J.
        • Nervi F.
        Sterol carrier protein-2 is involved in cholesterol transfer from the endoplasmic reticulum to the plasma membrane in human fibroblasts.
        J. Biol. Chem. 1995; 270: 18723-18726
        • Yamamoto R.
        • Kallen C.B.
        • Babalola G.O.
        • Rennert H.
        • Billheimer J.T.
        • Strauss j.F.
        Cloning and expression of a cDNA encoding human sterol carrier protein 2.
        Proc. Natl. Acad. Sci. USA. 1991; 88: 463-467
        • Hirai A.
        • Kino T.
        • Tokinaga K.
        • Tahara K.
        • Tamura Y.
        • Yoshida S.
        Regulation of sterol carrier protein-2 (SCP-2) gene expression in rat peritoneal macrophages during foam cell formation. A key role for free cholesterol content.
        J Clin. Invest. 1994; 94: 2215-2223
        • Kraemer R.
        • Pomerantz K.B.
        • Kesav S.
        • Scallen T.J.
        • Hajjar D.P.
        Cholesterol enrichment enhances ex-1520 Journal of Lipid Research Volume 38, 1997 pression of sterol carrier protein-2: implications for its function in intracellular cholesterol trafficking.
        J. Lipid Res. 1995; 36: 2630-2638
        • Baum C.
        • Reschly E.
        Sterol carrier protein-2 modulates cellular cholesterol metabolism by enhancing cholesterol transfer to the plasma membrane.
        Gastroenterology. 1996; 110: 1148
        • Puglielli L.
        • Rigotti A.
        • Amigo L.
        • Nunez L.
        • Greco A.V.
        • Santos M.J.
        • Nervi F.
        Modulation of intrahe-patic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport.
        Biochem. J. 1996; 317: 681-687
        • Ito T.
        • Kawata S.
        • Imai Y.
        • Kakimoto H.
        • Trzaskos J.M.
        • Matsuzawa Y.
        Hepatic cholesterol metabolism in patients with cholesterol gallstones enhanced intracellular transport of cholesterol.
        Gastroenterology. 1996; 110: 1619-1627
        • Lazarow P.B.
        • Moser H.W.
        Disorders of peroxisome biogenesis.
        in: Scriver C.R. Beaudet A.C. Sly W.S. Valle D. In The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York1995: 2287-2324
        • Brown M.S.
        • Goldstein j.L.
        Lipoprotein receptors in the liver.
        J. Clin. Invest. 1983; 72: 743-747
        • Sviridov D.
        • Fidge N.
        Pathway of cholesterol efflux from human hepatoma cells.
        Biochim. Biophys. Acta. 1995; 1256: 210-220
        • Gellisen I.C.
        • Brown A.J.
        • Mander E.L.
        • Krithar-ides L.
        • Dean R.T.
        • Jessup W.
        Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol.
        J. Biol. Chem. 1996; 271: 17852-17860
        • Kritharides L.
        • Jessup W.
        • Mander E.L.
        • Dean R.T.
        Apolipoprotein A-I-mediated efflux of sterols from oxidized LDLrloaded macrophages.
        Arterioscler. Thromb. Vase. Biol. 1995; 15: 276-289
        • Xu X.X.
        • Tabas I.
        Lipoproteins activate acyl coenzyme Axholesterol acyltransferase only after cellular cholesterol pools are expanded to a critical threshold level.
        J. Biol. Chem. 1991; 266: 17040-17048
        • Maor I.
        • Aviram M.
        Oxidized low density lipoprotein leads to macrophage accumulation of unes-terified cholesterol as a result of lysosomal trapping of the lipoprotein hydrolyzed cholesteryl ester.
        J. Lipid Res. 1994; 35: 803-819
        • Cao J.
        • Fales H.M.
        • Schaffner C.P.
        Cellular sterol accumulation stimulated by cholesterol 5[}-6(}-ep-oxide in J774 macrophages.
        Proc. Soc. Exp. Biol. Med. 1995; 209: 195-204
        • Trach C.C.
        • Wulfroth P.M.
        • Severs N.J.
        • Robe-nak H.
        Influence of native and modified lipoproteins on migration of mouse peritoneal macrophages'the effect of the antioxidants vitamin E and probucol.
        Eur. J. Cell Biol. 1996; 71: 199-205
        • Wang H.
        • Germain S.J.
        • Benfield P.P.
        • Gillies P.J.
        Gene expression of acyl CoAxholesterol acyltransferase is up-regulated in human monocytes during differentiation and foam cell formation.
        Arterioscler. Thromb. Vase. Biol. 1996; 16: 809-814
        • Okwu A.K.
        • Xu X.X.
        • Shiratori Y.
        • Tabas I.
        Regulation of the threshold for lipoprotein-induced acyl CoAxholesterol acyltransferase stimulation in macrophages by cellular sphingomyelin content.
        J. Lipid Res. 1994; 35: 644-655
        • Maor I.
        • Mandel H.
        • Aviram M.
        Macrophage uptake of oxidized LDL inhibits lysosomal sphingomyelinase, thus causing the accumulation of unesteri-fied cholesterol-sphingomyelin rich particles in the lysosomes..
        Arterioscler. Thromb. Vase. Biol. 1995; 15:: 1378-1387
        • Fielding P.E.
        • Vlodavsky I.
        • Gospdarowicz D.
        • Fielding C.J.
        Effect of contact inhibition on the regulation of cholesterol metabolism in cultured vascular endothelial cells..
        J. Biol. Chem. 1979; 254: 749-755
        • Wolfbauer G.
        • Glick J.M.
        • Minor L.K.
        • Roth-blat G.H.
        Development of the smooth muscle foam cell: uptake of macrophage lipid inclusions..
        Proc. Natl. Acad. Sci. USA. 1986; 83: 7760-7764
        • Fielding P.E.
        • Davison P.M.
        • Karasek M.A.
        • Fielding C.J.
        Regulation of sterol transport in human microvascular endothelial cells..
        J. Cell Biol. 1982; 94: 350-354