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Oxysterols and Oxysterol-Binding Proteins in Cellular Lipid Metabolism

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Cellular Lipid Metabolism

Abstract

Oxysterols are 27-carbon oxidized derivatives of cholesterol or by-products of cholesterol synthesis with multiple biological activities. The major oxysterols arise either via cholesterol oxidation by cytochrome P450 enzymes or via non-enzymatic autoxidation processes. Oxysterols are present in healthy tissues or plasma at very low levels but are found enriched in pathological structures such as atherosclerotic lesions. Their concentrations in serum are suggested to reflect increased in vivo lipid peroxidation due to oxidative stress. The suggested physiologic functions of oxysterols include transcriptional control of lipid metabolism mediated by liver X receptors and sterol regulatory element binding proteins, as well as modulation of a variety of signaling and differentiation events. The recently characterized family of cytoplasmic oxysterol-binding homologues (ORP proteins) is conserved throughout the eukaryotic kingdom. These proteins are suggested to act as lipid sensors/transporters with important roles in mediating the impacts of oxysterols and possibly other signaling lipids to the machineries governing cellular lipid metabolism, vesicle transport, and signaling cascades.

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References

  • Adams CM, Reitz J, De Brabander JK, Feramisco JD, Li L, Brown MS, Goldstein JL (2004) Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. J Biol Chem 279:52772–52780

    PubMed  CAS  Google Scholar 

  • Aghaloo TL, Amantea CM, Cowan CM, Richardson JA, Wu BM, Parhami F, Tetradis S (2007) Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo. J Orthop Res 25:1488–1497

    PubMed  CAS  Google Scholar 

  • Alphey L, Jimenez J, Glover D (1998) A Drosophila homologue of oxysterol binding protein (OSBP) - implications for the role of OSBP. Biochim Biophys Acta. 1395:159–164

    PubMed  CAS  Google Scholar 

  • Amarilio R, Ramachandran S, Sabanay H, Lev S (2005) Differential regulation of endoplasmic reticulum structure through VAP-Nir protein interaction. J Biol Chem 280:5934–5944

    PubMed  CAS  Google Scholar 

  • Anniss AM, Apostolopoulos J, Dworkin S, Purton LE, Sparrow RL (2002) An oxysterol-binding protein family identified in the mouse. DNA Cell Biol 21:571–580

    PubMed  CAS  Google Scholar 

  • Antonny B, Bigay J, Casella JF, Drin G, Mesmin B, Gounon P (2005) Membrane curvature and the control of GTP hydrolysis in Arf1 during COPI vesicle formation. Biochem Soc Trans 33:619–622

    PubMed  CAS  Google Scholar 

  • Apfel R, Benbrook D, Lernhardt E, Ortiz MA, Salbert G, Pfahl M (1994) A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol Cell Biol 14:7025–7035

    PubMed  CAS  Google Scholar 

  • Arca M, Natoli S, Micheletta F, Riggi S, Di Angelantonio E, Montali A, Antonini TM, Antonini R, Diczfalusy U, Iuliano L (2007) Increased plasma levels of oxysterols, in vivo markers of oxidative stress, in patients with familial combined hyperlipidemia: reduction during atorvastatin and fenofibrate therapy. Free Radic Biol Med 42:698–705

    PubMed  CAS  Google Scholar 

  • Avrova AO, Nawsheen T, Rokka V-M, Heilbronn J, Campbell E, Hein I, Gilroy EM, Cardle L, Bradshaw JE, Stewart HE, Fakim YJ, Loake G, Birch PRJ (2004) Potato oxysterol binding protein and cathepsin B are rapidly up-regulated in independent defence pathways that distinguish R gene-mediated and field resistences to Phytophthora infestans. Mol Plant Pathol 5:45–46

    PubMed  CAS  Google Scholar 

  • Babiker A, Andersson O, Lund E, Xiu RJ, Deeb S, Reshef A, Leitersdorf E, Diczfalusy U, Björkhem I (1997) Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein-mediated reverse cholesterol transport. J Biol Chem 272:26253–26261

    PubMed  CAS  Google Scholar 

  • Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD (2002a) Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell 3:271–282

    PubMed  CAS  Google Scholar 

  • Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (2002b) Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3:283–289

    PubMed  CAS  Google Scholar 

  • Bankaitis VA, Phillips S, Yanagisawa L, Li X, Routt S, Xie Z (2005) Phosphatidylinositol transfer protein function in the yeast Saccharomyces cerevisiae. Adv Enzyme Regul 45:155–170

    PubMed  CAS  Google Scholar 

  • Baumann NA, Sullivan DP, Ohvo-Rekilä H, Simonot C, Pottekat A, Klaassen Z, Beh CT, Menon AK (2005) Transport of newly synthesized sterol to the sterol-enriched plasma membrane occurs via nonvesicular equilibration. Biochemistry 44:5816–5826

    PubMed  CAS  Google Scholar 

  • Beh CT, Rine J (2004) A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution. J Cell Sci 117:2983–2996

    PubMed  CAS  Google Scholar 

  • Beh CT, Cool L, Phillips J, Rine J (2001) Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 157:1117–1140

    PubMed  CAS  Google Scholar 

  • Bensinger SJ, Bradley MN, Joseph SB, Zelcer N, Janssen EM, Hausner MA, Shih R, Parks JS, Edwards PA, Jamieson BD, Tontonoz P (2008) LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134:97–111

    PubMed  CAS  Google Scholar 

  • Beseme F, Astruc ME, Defay R, Descomps B, Crastes de Paulet A (1986) Characterization of oxysterol-binding protein in rat embryo fibroblasts and variations as a function of the cell cycle. Biochim Biophys Acta 886:96–108

    PubMed  CAS  Google Scholar 

  • Beseme F, Astruc ME, Defay R, Crastes de Paulet A (1987) Rat liver cytosol oxysterol-binding protein. Characterization and comparison with the HTC cell protein. FEBS Lett 210:97–103

    PubMed  CAS  Google Scholar 

  • Beyea MM, Heslop CL, Sawyez CG, Edwards JY, Markle JG, Hegele RA, Huff MW (2007) Selective up-regulation of LXR-regulated genes ABCA1, ABCG, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol. J Biol Chem 282:5207–5216

    PubMed  CAS  Google Scholar 

  • Biasi F, Leonarduzzi G, Vizio B, Zanetti D, Sevanian A, Sottero B, Verde V, Zingaro B, Chiarpotto E, Poli G (2004) Oxysterol mixtures prevent proapoptotic effects of 7-ketocholesterol in macrophages: implications for proatherogenic gene modulation. FASEB J 18:693–695

    PubMed  CAS  Google Scholar 

  • Bigay J, Casella JF, Drin G, Mesmin B, Antonny B (2005) ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif. EMBO J 24:2244–2253

    PubMed  CAS  Google Scholar 

  • Björkhem I (1986) Assay of unesterified 7-oxocholesterol in human serum by isotope dilution-mass spectrometry. Anal Biochem 154:497–501

    PubMed  Google Scholar 

  • Björkhem I, Diczfalusy U (2002) Oxysterols: friends, foes, or just fellow passengers. Arterioscler Thromb Vasc Biol 22:734–742

    PubMed  Google Scholar 

  • Björkhem I, Eggertsen G (2001) Genes involved in initial steps of bile acid synthesis. Curr Opin Lipidol 12:97–103

    PubMed  Google Scholar 

  • Björkhem I, Andersson O, Diczfalusy U, Sevastik B, Xiu RJ, Duan C, Lund E (1994) Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages. Proc Natl Acad Sci USA 91:8592–8596

    PubMed  Google Scholar 

  • Björkhem I, Lütjohann D, Breuer O, Sakinis A, Wennmalm A (1997) Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro. J Biol Chem 272:30178–30184

    PubMed  Google Scholar 

  • Bodin K, Andersson U, Rystedt E, Ellis E, Norlin M, Pikuleva I, Eggertsen G, Björkhem I, Diczfalusy U (2002) Metabolism of 4 beta -hydroxycholesterol in humans. J Biol Chem 277:31534–31540

    PubMed  CAS  Google Scholar 

  • Boissonneault GA, Hennig B, Ouyang CM (1991) Oxysterols, cholesterol biosynthesis, and vascular endothelial cell monolayer barrier function. Proc Soc Exp Biol Med 196:338–343

    PubMed  CAS  Google Scholar 

  • Botolin D, Wang Y, Christian B, Jump DB (2006) Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways. J Lipid Res 47:181–192

    PubMed  CAS  Google Scholar 

  • Bowden K, Ridgway ND (2008) Oxysterol binding protein (OSBP) negatively regulates ATP binding cassette transporter A1 (ABCA1) protein stability. J Biol Chem 283:18210–18217

    PubMed  CAS  Google Scholar 

  • Bretillon L, Siden A, Wahlund LO, Lutjohann D, Minthon L, Crisby M, Hillert J, Groth CG, Diczfalusy U, Björkhem I (2000) Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci Lett 293:87–90

    PubMed  CAS  Google Scholar 

  • Brown MS, Goldstein JL (1974) Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol. J Biol Chem 249:7306–7314

    PubMed  CAS  Google Scholar 

  • Brown AJ, Jessup W (1999) Oxysterols and atherosclerosis. Atherosclerosis 142:1–28

    PubMed  CAS  Google Scholar 

  • Brown AJ, Mander EL, Gelissen IC, Kritharides L, Dean RT, Jessup W (2000a) Cholesterol and oxysterol metabolism and subcellular distribution in macrophage foam cells. Accumulation of oxidized esters in lysosomes. J Lipid Res 41:226–237

    CAS  Google Scholar 

  • Brown AJ, Watts GF, Burnett JR, Dean RT, Jessup W (2000b) Sterol 27-hydroxylase acts on 7-ketocholesterol in human atherosclerotic lesions and macrophages in culture. J Biol Chem 275:27627–27633

    PubMed  CAS  Google Scholar 

  • Brown AJ, Sun L, Feramisco JD, Brown MS, Goldstein JL (2002) Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. Mol Cell 10:237–245

    PubMed  CAS  Google Scholar 

  • Carpenter KL, Taylor SE, Ballantine JA, Fussell B, Halliwell B, Mitchinson MJ (1993) Lipids and oxidised lipids in human atheroma and normal aorta. Biochim Biophys Acta 1167:121–130

    PubMed  CAS  Google Scholar 

  • Carpenter KL, Taylor SE, van der Veen C, Williamson BK, Ballantine JA, Mitchinson MJ (1995) Lipids and oxidised lipids in human atherosclerotic lesions at different stages of development. Biochim Biophys Acta 1256:141–150

    PubMed  Google Scholar 

  • Castrillo A, Joseph SB, Vaidya SA, Haberland M, Fogelman AM, Cheng G, Tontonoz P (2003) Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell 12:805–816

    PubMed  CAS  Google Scholar 

  • Chang YH, Abdalla DS, Sevanian A (1997) Characterization of cholesterol oxidation products formed by oxidative modification of low density lipoprotein. Free Radic Biol Med 23:202–214

    PubMed  CAS  Google Scholar 

  • Chen JJ, Lukyanenko Y, Hutson JC (2002) 25-hydroxycholesterol is produced by testicular macrophages during the early postnatal period and influences differentiation of Leydig cells in vitro. Biol Reprod 66:1336–1341

    PubMed  CAS  Google Scholar 

  • Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW (2007) Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5:73–79

    PubMed  CAS  Google Scholar 

  • Chisolm GM, Ma G, Irwin KC, Martin LL, Gunderson KG, Linberg LF, Morel DW, DiCorleto PE (1994) 7 beta-hydroperoxycholest-5-en-3 beta-ol, a component of human atherosclerotic lesions, is the primary cytotoxin of oxidized human low density lipoprotein. Proc Natl Acad Sci USA 91:11452–11456

    PubMed  CAS  Google Scholar 

  • Colles SM, Maxson JM, Carlson SG, Chisolm GM (2001) Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 11:131–138

    PubMed  CAS  Google Scholar 

  • Collier FM, Gregorio-King CC, Apostolopoulos J, Walder K, Kirkland MA (2003) ORP3 splice variants and their expression in human tissues and hematopoietic cells. DNA Cell Biol 22:1–9

    PubMed  CAS  Google Scholar 

  • Corcoran RB, Scott MP (2006) Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc Natl Acad Sci USA 103:8408–8413

    PubMed  CAS  Google Scholar 

  • Costet P, Luo Y, Wang N, Tall AR (2000) Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 275:28240–28245

    PubMed  CAS  Google Scholar 

  • D’Angelo G, Vicinauza M, Di Campli A, De Matteis MA (2008) The multiple roles of PtdIns(4)P - not just the precursor of PtdIns(4,5)P2. J Cell Sci 121:1955–1963

    PubMed  Google Scholar 

  • Daum G, Tuller G, Nemec T, Hrastnik C, Balliano G, Cattel L, Milla P, Rocco F, Conzelmann A, Vionnet C, Kelly DE, Kelly S, Schweizer E, Schuller HJ, Hojad U, Greiner E, Finger K (1999) Systematic analysis of yeast strains with possible defects in lipid metabolism. Yeast 15:601–614

    PubMed  CAS  Google Scholar 

  • Dawson PA, Ridgway ND, Slaughter CA, Brown MS, Goldstein JL (1989a) cDNA cloning and expression of oxysterol-binding protein, an oligomer with a potential leucine zipper. J Biol Chem 264:16798–16803

    PubMed  CAS  Google Scholar 

  • Dawson PA, Van der Westhuyzen DR, Goldstein JL, Brown MS (1989b) Purification of oxysterol binding protein from hamster liver cytosol. J Biol Chem 264:9046–9052

    PubMed  CAS  Google Scholar 

  • Deckert V, Brunet A, Lantoine F, Lizard G, Millanvoye-van Brussel E, Monier S, Lagrost L, David-Dufilho M, Gambert P, Devynck MA (1998) Inhibition by cholesterol oxides of NO release from human vascular endothelial cells. Arterioscler Thromb Vasc Biol 18:1054–1060

    PubMed  CAS  Google Scholar 

  • Defay RE, Astruc ME, Roussillon S, Descomps B, Crastes De Paulet A (1982) A specific hydroxysterol binding protein in human lymphocyte cytosol. Biochimie 64:331–339

    PubMed  CAS  Google Scholar 

  • Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Invest 116:561–570

    PubMed  CAS  Google Scholar 

  • DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP (2008) 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol Endocrinol 22:65–77

    PubMed  CAS  Google Scholar 

  • Dwyer JR, Sever N, Carlson M, Nelson SF, Beachy PA, Parhami F (2007) Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J Biol Chem 282:8959–8968

    PubMed  CAS  Google Scholar 

  • Dzeletovic S, Breuer O, Lund E, Diczfalusy U (1995) Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal Biochem 225:73–80

    PubMed  CAS  Google Scholar 

  • Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86:839–848

    PubMed  CAS  Google Scholar 

  • Endo K, Oyama T, Saiki A, Ban N, Ohira M, Koide N, Murano T, Watanabe H, Nishii M, Miura M, Sekine K, Miyashita Y, Shirai K (2008) Determination of serum 7-ketocholesterol concentrations and their relationships with coronary multiple risks in diabetes mellitus. Diabetes Res Clin Pract 80:63–68

    PubMed  CAS  Google Scholar 

  • Engel T, Kannenberg F, Fobker M, Nofer J-R, Bode G, Lueken A, Assmann G, Seedorf U (2007) Expression of ATP-binding cassette-transporter ABCG1 prevents cell death by transporting cytotoxic 7β-hydroxycholesterol. FEBS Lett 581:1673–1680

    PubMed  CAS  Google Scholar 

  • Erridge C, Webb DJ, Spickett CM (2007) 25-Hydroxycholesterol, 7beta-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages. Free Radic Res 41:260–266

    PubMed  CAS  Google Scholar 

  • Fairn GD, McMaster CR (2005a) Identification and assessment of the role of a nominal phospholipid binding region of ORP1S (oxysterol-binding-protein-related protein 1 short) in the regulation of vesicular transport. Biochem J 387:889–896

    PubMed  CAS  Google Scholar 

  • Fairn GD, McMaster CR (2005b) The roles of the human lipid-binding proteins ORP9S and ORP10S in vesicular transport. Biochem Cell Biol 83:631–636

    PubMed  CAS  Google Scholar 

  • Fairn GD, Curwin AJ, Stefan CJ, McMaster CR (2007) The oxysterol binding protein Kes1p regulates Golgi apparatus phosphatidylinositol-4-phosphate function. Proc Natl Acad Sci USA 104:15352–15357

    PubMed  CAS  Google Scholar 

  • Fang M, Kearns BG, Gedvilaite A, Kagiwada S, Kearns M, Fung MK, Bankaitis VA (1996) Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis. EMBO J 15:6447–6459

    PubMed  CAS  Google Scholar 

  • Forman BM, Ruan B, Chen J, Schroepfer GJ Jr, Evans RM (1997) The orphan nuclear receptor LXRalpha is positively and negatively regulated by distinct products of mevalonate metabolism. Proc Natl Acad Sci USA 94:10588–10593

    PubMed  CAS  Google Scholar 

  • Fuda H, Javitt NB, Mitamura K, Ikegawa S, Strott CA (2007) Oxysterols are substrates for cholesterol sulfotransferase. J Lipid Res 48:1343–1352

    PubMed  CAS  Google Scholar 

  • Fukuzawa M, Williams JG (2002) OSBPa, a predicted oxysterol binding protein of Dictyostelium, is required for regulated entry into culmination. FEBS Lett 527:37–42

    PubMed  CAS  Google Scholar 

  • Garcia-Cruset S, Carpenter KL, Guardiola F, Mitchinson MJ (1999) Oxysterols in cap and core of human advanced atherosclerotic lesions. Free Radic Res 30:341–50

    PubMed  CAS  Google Scholar 

  • Garcia-Cruset S, Carpenter KL, Guardiola F, Stein BK, Mitchinson MJ (2001) Oxysterol profiles of normal human arteries, fatty streaks and advanced lesions. Free Radic Res 35:31–41

    PubMed  CAS  Google Scholar 

  • Gelissen IC, Brown AJ, Mander EL, Kritharides L, Dean RT, Jessup W (1996) Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol. J Biol Chem 271:17852–17860

    PubMed  CAS  Google Scholar 

  • Gill S, Chow R, Brown AJ (2008) Sterol regulators of cholesterol homeostasis and beyond: the oxysterol hypothesis revisited and revised. Progr Lipid Res 47:391–404

    CAS  Google Scholar 

  • Godi A, Di Campli A, Konstantakopoulos A, Di Tullio G, Alessi DR, Kular GS, Daniele T, Marra P, Lucocq JM, De Matteis MA (2004) FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nat Cell Biol 6:393–404

    PubMed  CAS  Google Scholar 

  • Goldfinger LE, Ptak C, Jeffery ED, Shabanowitz J, Han J, Haling JR, Sherman NE, Fox JW, Hunt DF, Ginsberg MH (2007) An experimentally derived database of candidate Ras-interacting proteins. J Proteome Res 6:1806–1811

    PubMed  CAS  Google Scholar 

  • Goldstein JL, DeBose-Boyd RA, Brown MS (2006) Protein sensors for membrane sterols. Cell 124:35–46

    PubMed  CAS  Google Scholar 

  • Gregorio-King CC, Collier GR, McMillan JS, Waugh CM, McLeod JL, Collier FM, Kirkland MA (2001) ORP-3, a human oxysterol-binding protein gene differentially expressed in hematopoietic cells. Blood 98:2279–2281

    PubMed  CAS  Google Scholar 

  • Guyton JR, Black BL, Seidel CL (1990) Focal toxicity of oxysterols in vascular smooth muscle cell culture. A model of the atherosclerotic core region. Am J Pathol 137:425–434

    CAS  Google Scholar 

  • Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M (2003) Molecular machinery for non-vesicular trafficking of ceramide. Nature 426:803–809

    PubMed  CAS  Google Scholar 

  • Hanada M, Feng J, Hemmings BA (2004) Structure, regulation and function of PKB/AKT-a major therapeutic target. Biochim Biophys Acta 1697:3–16

    PubMed  CAS  Google Scholar 

  • Hayden JM, Brachova L, Higgins K, Obermiller L, Sevanian A, Khandrika S, Reaven PD (2002) Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. J Lipid Res 43:26–35

    PubMed  CAS  Google Scholar 

  • Henneberry AL, Sturley SL (2005) Sterol homeostasis in the budding yeast, Saccharomyces cerevisiae. Semin Cell Dev Biol 16:155–161

    PubMed  CAS  Google Scholar 

  • Hietter H, Trifilieff E, Richert L, Beck JP, Luu B, Ourisson G (1984) Antagonist action of cholesterol towards the toxicity of hydroxysterols on cultured hepatoma cells. Biochem Biophys Res Commun 120:657–664

    PubMed  CAS  Google Scholar 

  • Hojozi M, Munehira Y, Ikeda Y, Makishima M, Matsuo M, Kioka N, Ueda K (2008) Direct interaction of nuclear receptor LXRβ with ABCA1 modulates cholesterol efflux. J Biol Chem 283:30057–30063

    Google Scholar 

  • Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X (1993) 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 90:11603–11607

    PubMed  CAS  Google Scholar 

  • Hult M, Elleby B, Shafqat N, Svensson S, Rane A, Jornvall H, Abrahmsen L, Oppermann U (2004) Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. Cell Mol Life Sci 61:992–999

    PubMed  CAS  Google Scholar 

  • Hur HS, Ryu JH, Kim KH, Kim J (2006) Characterization of Osh3, an oxysterol-binding protein, in filamentous growth of Saccharomyces cerevisiae and Candida albicans. J Microbiol 44:523–529

    PubMed  CAS  Google Scholar 

  • Hynynen R, Laitinen S, Käkelä R, Tanhuanpää K, Lusa S, Ehnholm C, Somerharju P, Ikonen E, Olkkonen VM (2005) Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis. Biochem J 390:273–283

    PubMed  CAS  Google Scholar 

  • Ikonen E (2008) Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 9:125–138

    PubMed  CAS  Google Scholar 

  • Im YJ, Raychaudhuri S, Prinz WA, Hurley JH (2005) Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature 437:154–158

    PubMed  CAS  Google Scholar 

  • Infante RE, Abi-Mosleh L, Radhakrishnan A, Dale JD, Brown MS, Goldstein JL (2008a) Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein. J Biol Chem 283:1052–1063

    PubMed  CAS  Google Scholar 

  • Infante RE, Radhakrishnan A, Abi-Mosleh L, Kinch LN, Wang ML, Grishin NV, Goldstein JL, Brown MS (2008b) Purified NPC1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop. J Biol Chem 283:1064–10675

    PubMed  CAS  Google Scholar 

  • Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383:728–731

    PubMed  CAS  Google Scholar 

  • Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ (1999) Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA 96:266–271

    PubMed  CAS  Google Scholar 

  • Janowski BA, Shan B, Russell DW (2001) The hypocholesterolemic agent LY295427 reverses suppression of sterol regulatory element-binding protein processing mediated by oxysterols. J Biol Chem 276:45408–45416

    PubMed  CAS  Google Scholar 

  • Javitt NB (2004) Oxysteroids: a new class of steroids with autocrine and paracrine functions. Trends Endocrinol Metab 15:393–397

    PubMed  CAS  Google Scholar 

  • Javitt NB (2008) Oxysterols: novel biologic roles for the 21st century. Steroids 73:149–157

    PubMed  CAS  Google Scholar 

  • Jaworski CJ, Moreira E, Li A, Lee R, Rodriguez IR (2001) A family of 12 human genes containing oxysterol-binding domains. Genomics 78:185–196

    PubMed  CAS  Google Scholar 

  • Jiang B, Brown JL, Sheraton J, Fortin N, Bussey H (1994) A new family of yeast genes implicated in ergosterol synthesis is related to the human oxysterol binding protein. Yeast 10:341–353

    PubMed  CAS  Google Scholar 

  • Johansson M, Bocher V, Lehto M, Chinetti G, Kuismanen E, Ehnholm C, Staels B, Olkkonen VM (2003) The two variants of oxysterol binding protein-related protein-1 display different tissue expression patterns, have different intracellular localization, and are functionally distinct. Mol Biol Cell 14:903–915

    PubMed  CAS  Google Scholar 

  • Johansson M, Lehto M, Tanhuanpää K, Cover TL, Olkkonen VM (2005) The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments. Mol Biol Cell 16:5480–5492

    PubMed  CAS  Google Scholar 

  • Johansson M, Rocha N, Zwart W, Jordens I, Janssen L, Kuijl C, Olkkonen VM, Neefjes J (2007) Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin. J Cell Biol 176:459–471

    PubMed  CAS  Google Scholar 

  • Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, Collins JL, Osborne TF, Tontonoz P (2002) Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem 277:11019–11025

    PubMed  CAS  Google Scholar 

  • Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P (2003) Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 9:213–219

    PubMed  CAS  Google Scholar 

  • Kahn RA, Volpicelli-Daley L, Bowzard B, Shrivastava-Ranjan P, Li Y, Zhou C, Cunningham L (2005) Arf family GTPases: roles in membrane traffic and microtubule dynamics. Biochem Soc Trans 33:1269–1272

    PubMed  CAS  Google Scholar 

  • Kaiser SE, Brickner JH, Reilein AR, Fenn TD, Walter P, Brunger AT (2005) Structural basis of FFAT motif-mediated ER targeting. Structure 13:1035–1045

    PubMed  CAS  Google Scholar 

  • Käkelä R, Tanhuanpää K, Laitinen S, Somerharju P, Olkkonen VM (2005) Overexpression of OSBP-related protein 2 (ORP2) in CHO cells induces alterations of phospholipid species composition. Biochem Cell Biol 83:677–683

    PubMed  Google Scholar 

  • Kandutsch AA, Chen HW (1974) Inhibition of sterol synthesis in cultured mouse cells by cholesterol derivatives oxygenated in the side chain. J Biol Chem 249:6057–6061

    PubMed  CAS  Google Scholar 

  • Kandutsch AA, Shown EP (1981) Assay of oxysterol-binding protein in a mouse fibroblast, cell-free system. Dissociation constant and other properties of the system. J Biol Chem 256:13068–13073

    PubMed  CAS  Google Scholar 

  • Kandutsch AA, Thompson EB (1980) Cytosolic proteins that bind oxygenated sterols. Cellular distribution, specificity, and some properties. J Biol Chem 255:10813–10821

    PubMed  CAS  Google Scholar 

  • Kandutsch AA, Chen HW, Shown EP (1977) Binding of 25-hydroxycholesterol and cholesterol to different cytoplasmic proteins. Proc Natl Acad Sci USA 74:2500–2503

    PubMed  CAS  Google Scholar 

  • Kandutsch AA, Chen HW, Heiniger HJ (1978) Biological activity of some oxygenated sterols. Science 201:498–501

    PubMed  CAS  Google Scholar 

  • Kennedy MA, Venkateswaran A, Tarr PT, Xenarios I, Kudoh J, Shimizu N, Edwards PA (2001) Characterization of the human ABCG1 gene: liver X receptor activates an internal promoter that produces a novel transcript encoding an alternative form of the protein. J Biol Chem 276:39438–39447

    PubMed  CAS  Google Scholar 

  • Kha HT, Basseri B, Shouhed D, Richardson J, Tetradis S, Hahn TJ, Parhami F (2004) Oxysterols regulate differentiation of mesenchymal stem cells: pro-bone and anti-fat. J Bone Miner Res 19:830–840

    PubMed  CAS  Google Scholar 

  • Kim WK, Meliton V, Amantea CM, Hahn TJ, Parhami F (2007) 20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism. J Bone Miner Res 22:1711–1719

    PubMed  CAS  Google Scholar 

  • Kinbara K, Goldfinger LE, Hansen M, Chou FL, Ginsberg MH (2003) Ras GTPases: integrins’ friends or foes. Nat Rev Mol Cell Biol 4:767–776

    PubMed  CAS  Google Scholar 

  • Knutsen Rydberg E, Salomonsson L, Hulten LM, Noren K, Bondjers G, Wiklund O, Bjornheden T, Ohlsson BG (2003) Hypoxia increases 25-hydroxycholesterol-induced interleukin-8 protein secretion in human macrophages. Atherosclerosis 170:245–252

    Google Scholar 

  • Kolsch H, Lutjohann D, von Bergmann K, Heun R (2003) The role of 24S-hydroxycholesterol in Alzheimer’s disease. J Nutr Health Aging 7:37–41

    PubMed  CAS  Google Scholar 

  • Kozminski KG, Alfaro G, Dighe S, Beh CT (2006) Homologues of oxysterol-binding proteins affect Cdc42p- and Rho1p-mediated cell polarization in Saccharomyces cerevisiae. Traffic 7:1–19

    Google Scholar 

  • Kritharides L, Jessup W, Mander EL, Dean RT (1995) Apolipoprotein A-I-mediated efflux of sterols from oxidized LDL-loaded macrophages. Arterioscler Thromb Vasc Biol 15:276–289

    PubMed  CAS  Google Scholar 

  • Kvam E, Goldfarb DS (2004) Nvj1p is the outer-nuclear-membrane receptor for oxysterol-binding protein homolog Osh1p in Saccharomyces cerevisiae. J Cell Sci 117:4959–4968

    PubMed  CAS  Google Scholar 

  • Lagace TA, Byers DM, Cook HW, Ridgway ND (1997) Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese-hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. Biochem J 326:205–213

    PubMed  CAS  Google Scholar 

  • Lagace TA, Byers DM, Cook HW, Ridgway ND (1999) Chinese hamster ovary cells overexpressing the oxysterol binding protein (OSBP) display enhanced synthesis of sphingomyelin in response to 25-hydroxycholesterol. J Lipid Res 40:109–116

    PubMed  CAS  Google Scholar 

  • Laitinen S, Lehto M, Lehtonen S, Hyvärinen K, Heino S, Lehtonen E, Ehnholm C, Ikonen E, Olkkonen VM (2002) ORP2, a homolog of oxysterol binding protein, regulates cellular cholesterol metabolism. J Lipid Res 43:245–255

    PubMed  CAS  Google Scholar 

  • Lange Y, Ye J, Strebel F (1995) Movement of 25-hydroxycholesterol from the plasma membrane to the rough endoplasmic reticulum in cultured hepatoma cells. J Lipid Res 36:1092–1097

    PubMed  CAS  Google Scholar 

  • Lange Y, Ory DS, Ye J, Lanier MH, Hsu FF, Steck TL (2008) Effectors of rapid homeostatic responses of endoplasmic reticulum cholesterol and 3-hydroxy-3-methylglutaryl-CoA reductase. J Biol Chem 283:1445–1455

    PubMed  CAS  Google Scholar 

  • Larsson DA, Baird S, Nyhalah JD, Yuan XM, Li W (2006) Oxysterol mixtures, in atheroma-relevant proportions, display synergistic and proapoptotic effects. Free Radic Biol Med 41:902–910

    PubMed  CAS  Google Scholar 

  • Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM (1997) Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem 272:3137–3140

    PubMed  CAS  Google Scholar 

  • Lehto M, Olkkonen VM (2003) The OSBP-related proteins: a novel protein family involved in vesicle transport, cellular lipid metabolism, and cell signalling. Biochim Biophys Acta 1631:1–11

    PubMed  CAS  Google Scholar 

  • Lehto M, Laitinen S, Chinetti G, Johansson M, Ehnholm C, Staels B, Ikonen E, Olkkonen VM (2001) The OSBP-related protein family in humans. J Lipid Res 42:1203–1213

    PubMed  CAS  Google Scholar 

  • Lehto M, Tienari J, Lehtonen S, Lehtonen E, Olkkonen VM (2004) Subfamily III of mammalian oxysterol-binding protein (OSBP) homologues: the expression and intracellular localization of ORP3, ORP6, and ORP7. Cell Tissue Res 315:39–57

    PubMed  CAS  Google Scholar 

  • Lehto M, Hynynen R, Karjalainen K, Kuismanen E, Hyvarinen K, Olkkonen VM (2005) Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. Exp Cell Res 310:445–462

    PubMed  CAS  Google Scholar 

  • Lehto M, Mäyränpää MI, Pellinen T, Po I, Lehtonen S, Kovanen PT, Groop P-H, Ivaska J, Olkkonen VM (2008) The R-Ras interaction partner ORP3 regulates cell adhesion. J Cell Sci 121:695–705

    PubMed  CAS  Google Scholar 

  • Lemaire-Ewing S, Prunet C, Montange T, Vejux A, Berthier A, Bessede G, Corcos L, Gambert P, Neel D, Lizard G (2005) Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols. Cell Biol Toxicol 21:97–114

    PubMed  CAS  Google Scholar 

  • Lemaire-Ewing S, Berthier A, Royer MC, Logette E, Corcos L, Bouchot A, Monier S, Prunet C, Raveneau M, Rebe C, Desrumaux C, Lizard G, Neel D (2008) 7β-Hydroxycholesterol and 25-hydroxycholesterol-induced interleukin-8 secretion involves a calcium-dependent activation of c-fos via the ERK1/2 signaling pathway in THP-1 cells: oxysterols-induced IL-8 secretion is calcium-dependent. Cell Biol Toxicol (in press), DOI: PMID 18317936

    Google Scholar 

  • Leonarduzzi G, Biasi F, Chiarpotto E, Poli G (2004) Trojan horse-like behavior of a biologically representative mixture of oxysterols. Mol Aspects Med 25:155–167

    PubMed  CAS  Google Scholar 

  • Leonarduzzi G, Gamba P, Sottero B, Kadl A, Robbesyn F, Calogero RA, Biasi F, Chiarpotto E, Leitinger N, Sevanian A, Poli G (2005) Oxysterol-induced up-regulation of MCP-1 expression and synthesis in macrophage cells. Free Radic Biol Med 39:1152–1161

    PubMed  CAS  Google Scholar 

  • Leoni V, Masterman T, Diczfalusy U, De Luca G, Hillert J, Björkhem I (2002) Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis. Neurosci Lett 331:163–166

    PubMed  CAS  Google Scholar 

  • Lessmann E, Ngo M, Leitges M, Minguet S, Ridgway ND, Huber M (2007) Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation. Cell Signal 19:384–392

    PubMed  CAS  Google Scholar 

  • Lev S (2004) The role of the Nir/rdgB protein family in membrane trafficking and cytoskeleton remodeling. Exp Cell Res 297:1–10

    PubMed  CAS  Google Scholar 

  • Levanon D, Hsieh CL, Francke U, Dawson PA, Ridgway ND, Brown MS, Goldstein JL (1990) cDNA cloning of human oxysterol-binding protein and localization of the gene to human chromosome 11 and mouse chromosome 19. Genomics 7:65–74

    PubMed  CAS  Google Scholar 

  • Levine T (2004) Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions. Trends Cell Biol 14:483–490

    PubMed  CAS  Google Scholar 

  • Levine TP, Munro S (1998) The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes. Curr Biol 8:729–739

    PubMed  CAS  Google Scholar 

  • Levine TP, Munro S (2001) Dual targeting of Osh1p, a yeast homologue of oxysterol-binding protein, to both the Golgi and the nucleus-vacuole junction. Mol Biol Cell 12:1633–1644

    PubMed  CAS  Google Scholar 

  • Levine TP, Munro S (2002) Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components. Curr Biol 12:695–704

    PubMed  CAS  Google Scholar 

  • Li AC, Glass CK (2004) PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis. J Lipid Res 45:2161–2173

    PubMed  CAS  Google Scholar 

  • Li DY, Inoue H, Takahashi M, Kojima T, Shiraiwa M, Takahara H (2008) Molecular characterization of a novel salt-inducible gene for an OSBP (oxysterol-binding protein)-homologue from soybean. Gene 407:12–20

    PubMed  CAS  Google Scholar 

  • Li W, Dalen H, Eaton JW, Yuan XM (2001) Apoptotic death of inflammatory cells in human atheroma. Arterioscler Thromb Vasc Biol 21:1124–1130

    PubMed  CAS  Google Scholar 

  • Li X, Rivas MP, Fang M, Marchena J, Mehrotra B, Chaudhary A, Feng L, Prestwich GD, Bankaitis VA (2002) Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex. J Cell Biol 157:63–77

    PubMed  CAS  Google Scholar 

  • Li X, Pandak WM, Erickson SK, Ma Y, Yin L, Hylemon P, Ren S (2007) Biosynthesis of the regulatory oxysterol, 5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res 48:2587–2596

    PubMed  CAS  Google Scholar 

  • Li Y, Prinz WA (2004) ATP-binding cassette (ABC) transporters mediate nonvesicular, raft-modulated sterol movement from the plasma membrane to the endoplasmic reticulum. J Biol Chem 279:45226–45234

    PubMed  CAS  Google Scholar 

  • Li-Hawkins J, Lund EG, Turley SD, Russell DW (2000) Disruption of the oxysterol 7alpha-hydroxylase gene in mice. J Biol Chem 275:16536–16542

    PubMed  CAS  Google Scholar 

  • Loewen CJ, Roy A, Levine TP (2003) A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. EMBO J 22:2025–2035

    PubMed  CAS  Google Scholar 

  • Loewen CJ, Gaspar ML, Jesch SA, Delon C, Ktistakis NT, Henry SA, Levine TP (2004) Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid. Science 304:1644–1647

    PubMed  CAS  Google Scholar 

  • Lordan S, O’Callaghan YC, O’Brien NM (2007) Death-signaling pathways in human myeloid cells by oxLDL and its cytotoxic components 7beta-hydroxycholesterol and cholesterol-5beta,6beta-epoxide. J Biochem Mol Toxicol 21:362–372

    PubMed  CAS  Google Scholar 

  • Lund E, Björkhem I, Furster C, Wikvall K (1993) 24-, 25- and 27-hydroxylation of cholesterol by a purified preparation of 27-hydroxylase from pig liver. Biochim Biophys Acta 1166:177–182

    PubMed  CAS  Google Scholar 

  • Lund EG, Kerr TA, Sakai J, Li WP, Russell DW (1998) cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. J Biol Chem 273:34316–34327

    PubMed  CAS  Google Scholar 

  • Luoma PV (2007) Cytochrome P450 - physiological key factor against cholesterol accumulation and the atherosclerotic vascular process. Ann Med 39:359–370

    PubMed  CAS  Google Scholar 

  • Luthra S, Dong J, Gramajo AL, Chwa M, Kim DW, Neekhra A, Kuppermann BD, Kenney MC (2007) 7-Ketocholesterol activates caspases-3/7, -8, and -12 in human microvascular endothelial cells in vitro. Microvasc Res 75:343–350

    Google Scholar 

  • Lütjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, Björkhem I (1996) Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA 93:9799–804

    PubMed  Google Scholar 

  • Lütjohann D, Papassotiropoulos A, Björkhem I, Locatelli S, Bagli M, Oehring RD, Schlegel U, Jessen F, Rao ML, von Bergmann K, Heun R (2000) Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res 41:195–198

    PubMed  Google Scholar 

  • Lyons MA, Brown AJ (2001a) 7-Ketocholesterol delivered to mice in chylomicron remnant-like particles is rapidly metabolised, excreted and does not accumulate in aorta. Biochim Biophys Acta 1530:209–218

    PubMed  CAS  Google Scholar 

  • Lyons MA, Brown AJ (2001b) Metabolism of an oxysterol, 7-ketocholesterol, by sterol 27-hydroxylase in HepG2 cells. Lipids 36:701–711

    PubMed  CAS  Google Scholar 

  • Lyons MA, Samman S, Gatto L, Brown AJ (1999) Rapid hepatic metabolism of 7-ketocholesterol in vivo: implications for dietary oxysterols. J Lipid Res 40:1846–1857

    PubMed  CAS  Google Scholar 

  • Maor I, Kaplan M, Hayek T, Vaya J, Hoffman A, Aviram M (2000) Oxidized monocyte-derived macrophages in aortic atherosclerotic lesion from apolipoprotein E-deficient mice and from human carotid artery contain lipid peroxides and oxysterols. Biochem Biophys Res Commun 269:775–780

    PubMed  CAS  Google Scholar 

  • Marchant CE, Van der Veen C, Law NS, Hardwick SJ, Carpenter KL, Mitchinson MJ (1996) Oxidation of low-density lipoprotein by human monocyte-macrophages results in toxicity to the oxidising culture. Free Radic Res 24:333–342

    PubMed  CAS  Google Scholar 

  • Mark M, Muller P, Maier R, Eisele B (1996) Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells. J Lipid Res 37:148–158

    PubMed  CAS  Google Scholar 

  • Mattsson-Hulten L, Lindmark H, Diczfalusy U, Björkhem I, Ottosson M, Liu Y, Bondjers G, Wiklund O (1996) Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages. J Clin Invest 97:461–468

    Google Scholar 

  • Millanvoye-Van Brussel E, Topal G, Brunet A, Do Pham T, Deckert V, Rendu F, David-Dufilho M (2004) Lysophosphatidylcholine and 7-oxocholesterol modulate Ca2+ signals and inhibit the phosphorylation of endothelial NO synthase and cytosolic phospholipase A2. Biochem J 380:533–539

    PubMed  CAS  Google Scholar 

  • Mohammadi A, Perry RJ, Storey MK, Cook HW, Byers DM, Ridgway ND (2001) Golgi localization and phosphorylation of oxysterol binding protein in Niemann-Pick C and U18666A-treated cells. J Lipid Res 42:1062–1071

    PubMed  CAS  Google Scholar 

  • Monier S, Samadi M, Prunet C, Denance M, Laubriet A, Athias A, Berthier A, Steinmetz E, Jurgens G, Negre-Salvayre A, Bessede G, Lemaire-Ewing S, Neel D, Gambert P, Lizard G (2003) Impairment of the cytotoxic and oxidative activities of 7 beta-hydroxycholesterol and 7-ketocholesterol by esterification with oleate. Biochem Biophys Res Commun 303:814–824

    PubMed  CAS  Google Scholar 

  • Moreira EF, Jaworski C, Li A, Rodriguez IR (2001) Molecular and biochemical characterization of a novel oxysterol-binding protein (OSBP2) highly expressed in retina. J Biol Chem 276:18570–18578

    PubMed  CAS  Google Scholar 

  • Morel DW, Edgerton ME, Warner GE, Johnson WJ, Phillips MC, Rothblat GH (1996) Comparison of the intracellular metabolism and trafficking of 25-hydroxycholesterol and cholesterol in macrophages. J Lipid Res 37:2041–2051

    PubMed  CAS  Google Scholar 

  • Nelson JA, Steckbeck SR, Spencer TA (1981) Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide. J Biol Chem 256:1067–1068

    PubMed  CAS  Google Scholar 

  • Nishimura T, Inoue T, Shibata N, Sekine A, Takabe W, Noguchi N, Arai H (2005) Inhibition of cholesterol biosynthesis by 25-hydroxycholesterol is independent of OSBP. Genes Cells 10:793–801

    PubMed  CAS  Google Scholar 

  • Norlin M, Andersson U, Björkhem I, Wikvall K (2000a) Oxysterol 7 alpha-hydroxylase activity by cholesterol 7 alpha-hydroxylase (CYP7A). J Biol Chem 275:34046–34053

    PubMed  CAS  Google Scholar 

  • Norlin M, Toll A, Björkhem I, Wikvall K (2000b) 24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A). J Lipid Res 41:1629–1639

    PubMed  CAS  Google Scholar 

  • Ohtsuka M, Miyashita Y, Shirai K (2006) Lipids deposited in human atheromatous lesions induce apoptosis of human vascular smooth muscle cells. J Atheroscler Thromb 13:256–262

    PubMed  CAS  Google Scholar 

  • Olkkonen VM, Lehto M (2004) Oxysterols and oxysterol binding proteins: role in lipid metabolism and atherosclerosis. Ann Med 36:562–572

    PubMed  CAS  Google Scholar 

  • Olkkonen VM, Levine TP (2004) Oxysterol binding proteins: in more than one place at one time. Biochem Cell Biol 82:87–98

    PubMed  CAS  Google Scholar 

  • Ouimet M, Wang M-D, Cadotte N, Ho K, Marcel YL (2008) Epoxycholesterol impairs cholesterol ester hydrolysis in macrophage foam cells, resulting in decreased cholesterol efflux. Arterioscler Thromb Vasc Biol 28:1144–1150

    PubMed  CAS  Google Scholar 

  • Oram JF, Vaughan AM (2006) ATP-Binding cassette cholesterol transporters and cardiovascular disease. Circ Res 99:1031–1043

    PubMed  CAS  Google Scholar 

  • Panzenboeck U, Andersson U, Hansson M, Sattler W, Meaney S, Björkhem I (2007) On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis. J Lipid Res 48:1167–1174

    PubMed  CAS  Google Scholar 

  • Park YU, Hwang O, Kim J (2002) Two-hybrid cloning and characterization of OSH3, a yeast oxysterol-binding protein homolog. Biochem Biophys Res Commun 293:733–740

    PubMed  CAS  Google Scholar 

  • Peretti D, Dahan N, Shimoni E, Hirschberg K, Lev S (2008) Coordinated lipid transfer between the ebnoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol Biol Cell 19:3871–3884

    PubMed  CAS  Google Scholar 

  • Perry RJ, Ridgway ND (2006) Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein. Mol Biol Cell 17:2604–2616

    PubMed  CAS  Google Scholar 

  • Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL (2007) Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc Natl Acad Sci USA 104:6511–6518

    PubMed  CAS  Google Scholar 

  • Ramachandra RK, Lankford SE, Weber GM, Rexroad CE, 3rd, Yao J (2007) Identification of OORP-T, a novel oocyte-specific gene encoding a protein with a conserved oxysterol binding protein domain in rainbow trout. Mol Reprod Dev 74:502–511

    PubMed  CAS  Google Scholar 

  • Raychaudhuri S, Im YJ, Hurley JH, Prinz WA (2006) Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides. J Cell Biol 173:107–119

    PubMed  CAS  Google Scholar 

  • Repa JJ, Mangelsdorf DJ (2000) The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 16:459–481

    PubMed  CAS  Google Scholar 

  • Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ (2000a) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14:2819–2830

    PubMed  CAS  Google Scholar 

  • Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, Heyman RA, Dietschy JM, Mangelsdorf DJ (2000b) Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289:1524–1529

    PubMed  CAS  Google Scholar 

  • Richardson JA, Amantea CM, Kianmahd B, Tetradis S, Lieberman JR, Hahn TJ, Parhami F (2007) Oxysterol-induced osteoblastic differentiation of pluripotent mesenchymal cells is mediated through a PKC- and PKA-dependent pathway. J Cell Biochem 100:1131–1145

    PubMed  CAS  Google Scholar 

  • Ridgway ND, Dawson PA, Ho YK, Brown MS, Goldstein JL (1992) Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. J Cell Biol 116:307–319

    PubMed  CAS  Google Scholar 

  • Ridgway ND, Lagace TA, Cook HW, Byers DM (1998) Differential effects of sphingomyelin hydrolysis and cholesterol transport on oxysterol-binding protein phosphorylation and Golgi localization. J Biol Chem 273:31621–31628

    PubMed  CAS  Google Scholar 

  • Rimner A, Al Makdessi S, Sweidan H, Wischhusen J, Rabenstein B, Shatat K, Mayer P, Spyridopoulos I (2005) Relevance and mechanism of oxysterol stereospecifity in coronary artery disease. Free Radic Biol Med 38:535–544

    PubMed  CAS  Google Scholar 

  • Romeo GR, Kazlauskas A (2008) Oxysterol and diabetes activate STAT3, and control endothelial expression of profilin-1 via OSBP1. J Biol Chem 283:9595–9605

    PubMed  CAS  Google Scholar 

  • Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Björkhem I, Seckl J, Lathe R (1997) Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone. Proc Natl Acad Sci USA 94:4925–4930

    PubMed  CAS  Google Scholar 

  • Rowe AH, Argmann CA, Edwards JY, Sawyez CG, Morand OH, Hegele RA, Huff MW (2003) Enhanced synthesis of the oxysterol 24(S),25-epoxycholesterol in macrophages by inhibitors of 2,3-oxidosqualene:lanosterol cyclase: a novel mechanism for the attenuation of foam cell formation. Circ Res 93:717–725

    PubMed  CAS  Google Scholar 

  • Roy A, Levine TP (2004) Multiple pools of phosphatidylinositol 4-phosphate detected using the pleckstrin homology domain of Osh2p. J Biol Chem 279:44683–44689

    PubMed  CAS  Google Scholar 

  • Russell DW (2000) Oxysterol biosynthetic enzymes. Biochim Biophys Acta 1529:126–135

    PubMed  CAS  Google Scholar 

  • Sabol SL, Brewer HB, Jr., Santamarina-Fojo S (2005) The human ABCG1 gene: identification of LXR response elements that modulate expression in macrophages and liver. J Lipid Res 46:2151–2167

    PubMed  CAS  Google Scholar 

  • Saito E, Wachi H, Saro F, Seyama Y (2008) 7-ketocholesterol, a major oxysterol, promotes Pi-induced vascular calcification in cultured smooth muscle cells. J Atheroscler Thromb 15:130–137

    PubMed  CAS  Google Scholar 

  • Salonen JT, Nyyssonen K, Salonen R, Porkkala-Sarataho E, Tuomainen TP, Diczfalusy U, Björkhem I (1997) Lipoprotein oxidation and progression of carotid atherosclerosis. Circulation 95:840–845

    PubMed  CAS  Google Scholar 

  • Schmalix WA, Bandlow W (1994) SWH1 from yeast encodes a candidate nuclear factor containing ankyrin repeats and showing homology to mammalian oxysterol-binding protein. Biochim Biophys Acta 1219:205–210

    PubMed  CAS  Google Scholar 

  • Schroepfer GJ Jr (2000) Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 80:361–554

    PubMed  CAS  Google Scholar 

  • Schulz TA, Prinz WA (2007) Sterol transport in yeast and the oxysterol binding protein homologue (OSH) family. Biochim Biophys Acta 1771:769–780

    PubMed  CAS  Google Scholar 

  • Schweizer RA, Zurcher M, Balazs Z, Dick B, Odermatt A (2004) Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme. J Biol Chem 279:18415–18424

    PubMed  CAS  Google Scholar 

  • Sevanian A, Hodis HN, Hwang J, McLeod LL, Peterson H (1995) Characterization of endothelial cell injury by cholesterol oxidation products found in oxidized LDL. J Lipid Res 36:1971–1986

    PubMed  CAS  Google Scholar 

  • Sevanian A, Bittolo-Bon G, Cazzolato G, Hodis H, Hwang J, Zamburlini A, Maiorino M, Ursini F (1997) LDL- is a lipid hydroperoxide-enriched circulating lipoprotein. J Lipid Res 38:419–428

    PubMed  CAS  Google Scholar 

  • Siems W, Quast S, Peter D, Augustin W, Carluccio F, Grune T, Sevanian A, Hampl H, Wiswedel I (2005) Oxysterols are increased in plasma of end-stage renal disease patients. Kidney Blood Press Res 28:302–306

    PubMed  CAS  Google Scholar 

  • Skirpan AL, Dowd PE, Sijacic P, Jaworski CJ, Gilroy S, Kao TH (2006) Identification and characterization of PiORP1, a Petunia oxysterol-binding-protein related protein involved in receptor-kinase mediated signaling in pollen, and analysis of the ORP gene family in Arabidopsis. Plant Mol Biol 61:553–565

    PubMed  CAS  Google Scholar 

  • Smith LL, Teng JI, Lin YY, Seitz PK, McGehee MF (1981) Sterol metabolism XLVII. Oxidized cholesterol esters in human tissues. J Steroid Biochem 14:889–900

    PubMed  CAS  Google Scholar 

  • Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924

    PubMed  CAS  Google Scholar 

  • Storey MK, Byers DM, Cook HW, Ridgway ND (1998) Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. Biochem J 336:247–256

    PubMed  CAS  Google Scholar 

  • Sturley SL, Patterson MC, Balch W, Liscum L (2004) The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta 1685:83–87

    PubMed  CAS  Google Scholar 

  • Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M, Saarinen H, Radzikowska A, Thiele C, Olkkonen VM (2007) The mammalian OSBP-related proteins (ORP) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem J 405:473–480

    PubMed  CAS  Google Scholar 

  • Sugano S, Miura R, Morishima N (1996) Identification of intermediates in the conversion of cholesterol to pregnenolone with a reconstituted cytochrome p-450scc system: accumulation of the intermediate modulated by the adrenodoxin level. J Biochem 120:780–787

    PubMed  CAS  Google Scholar 

  • Sugawara K, Morita K, Ueno N, Shibuya H (2001) BIP, a BRAM-interacting protein involved in TGF-beta signalling, regulates body length in Caenorhabditis elegans. Genes Cells 6:599–606

    PubMed  CAS  Google Scholar 

  • Sullivan DP, Ohvo-Rekila H, Baumann NA, Beh CT, Menon AK (2006) Sterol trafficking between the endoplasmic reticulum and plasma membrane in yeast. Biochem Soc Trans 34:356–358

    PubMed  CAS  Google Scholar 

  • Sun LP, Seemann J, Goldstein JL, Brown MS (2007) Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci USA 104:6519–6526

    PubMed  CAS  Google Scholar 

  • Sung SC, Kim K, Lee KA, Choi KH, Kim SM, Son YH, Moon YS, Eo SK, Rhim BY (2008) 7-ketocholesterol upregulates interleukin-6 via mechanisms that are distinct from those of tumor necrosis factor-alpha, in vascular smooth muscle cells. J Vasc Res 46:36–44

    PubMed  Google Scholar 

  • Tam SP, Mok L, Chimini G, Vasa M, Deeley RG (2006) ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of oxysterol by intact cells. Am J Physiol Cell Physiol 291:C490–C502

    Google Scholar 

  • Taylor FR, Kandutsch AA (1985) Oxysterol binding protein. Chem Phys Lipids 38:187–194

    PubMed  CAS  Google Scholar 

  • Taylor FR, Saucier SE, Shown EP, Parish EJ, Kandutsch AA (1984) Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase. J Biol Chem 259:12382–12387

    PubMed  CAS  Google Scholar 

  • Taylor FR, Shown EP, Thompson EB, Kandutsch AA (1989) Purification, subunit structure, and DNA binding properties of the mouse oxysterol receptor. J Biol Chem 264:18433–18439

    PubMed  CAS  Google Scholar 

  • Terasaka N, Wang N, Yvan-Charvet L, Tall AR (2007) High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1. Proc Natl Acad Sci USA 104:15093–15098

    PubMed  CAS  Google Scholar 

  • Tertov VV, Sobenin IA, Gabbasov ZA, Popov EG, Jaakkola O, Solakivi T, Nikkari T, Smirnov VN, Orekhov AN (1992) Multiple-modified desialylated low density lipoproteins that cause intracellular lipid accumulation. Isolation, fractionation and characterization. Lab Invest 67:665–675

    PubMed  CAS  Google Scholar 

  • Tertov VV, Sobenin IA, Orekhov AN, Jaakkola O, Solakivi T, Nikkari T (1996) Characteristics of low density lipoprotein isolated from circulating immune complexes. Atherosclerosis 122:191–199

    PubMed  CAS  Google Scholar 

  • Theunissen JJ, Jackson RL, Kempen HJ, Demel RA (1986) Membrane properties of oxysterols. Interfacial orientation, influence on membrane permeability and redistribution between membranes. Biochim Biophys Acta 860:66–74

    PubMed  CAS  Google Scholar 

  • Tontonoz P, Mangelsdorf DJ (2003) Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol 17:985–993

    PubMed  CAS  Google Scholar 

  • Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, Korach KS, Shaul PW, Mangelsdorf DJ (2007) 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13:1185–1192

    PubMed  CAS  Google Scholar 

  • van de Bovenkamp P, Kosmeijer-Schuil TG, Katan MB (1988) Quantification of oxysterols in Dutch foods: egg products and mixed diets. Lipids 23:1079–1085

    PubMed  CAS  Google Scholar 

  • Varjosalo M, Taipale J (2007) Hedgehog signaling. J Cell Sci 120:3–6

    PubMed  CAS  Google Scholar 

  • Wang C, JeBailey L, Ridgway ND (2002) Oxysterol-binding-protein (OSBP)-related protein 4 binds 25-hydroxycholesterol and interacts with vimentin intermediate filaments. Biochem J 361:461–472

    PubMed  CAS  Google Scholar 

  • Wang P, Duan W, Munn AL, Yang H (2005a) Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae. FEBS J 272:4703–4715

    PubMed  CAS  Google Scholar 

  • Wang P, Zhang Y, Li H, Chieu HK, Munn AL, Yang H (2005b) AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. EMBO J 24:2989–2999

    PubMed  CAS  Google Scholar 

  • Wang PY, Weng J, Anderson RG (2005c) OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science 307:1472–1476

    PubMed  CAS  Google Scholar 

  • Wang PY, Weng J, Lee S, Anderson RG (2008a) N-terminus controls sterol binding while c-terminus regulates scaffolding function of OSBP. J Biol Chem 283:8034–8045

    PubMed  CAS  Google Scholar 

  • Wang X, Briggs MR, Hua X, Yokoyama C, Goldstein JL, Brown MS (1993) Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. II. Purification and characterization. J Biol Chem 268:14497–14504

    PubMed  CAS  Google Scholar 

  • Wang Y, Rogers P, Su C, Varga G, Stayrook KR, Burris TP (2008b) Regulation of cholesterologenesis by the oxysterol receptor, LXRα. J Biol Chem 283:26332–26339

    PubMed  CAS  Google Scholar 

  • Wassif CA, Yu J, Cui J, Porter FD, Javitt NB (2003) 27-Hydroxylation of 7- and 8-dehydrocholesterol in Smith-Lemli-Opitz syndrome: a novel metabolic pathway. Steroids 68:497–502

    PubMed  CAS  Google Scholar 

  • Vaya J, Aviram M, Mahmood S, Hayek T, Grenadir E, Hoffman A, Milo S (2001) Selective distribution of oxysterols in atherosclerotic lesions and human plasma lipoproteins. Free Radic Res 34:485–497

    PubMed  CAS  Google Scholar 

  • Venkateswaran A, Repa JJ, Lobaccaro JM, Bronson A, Mangelsdorf DJ, Edwards PA (2000) Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J Biol Chem 275:14700–14707

    PubMed  CAS  Google Scholar 

  • Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ (1995) LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev 9:1033–1045

    PubMed  CAS  Google Scholar 

  • Wong J, Quinn CM, Brown AJ (2004) Statins inhibit synthesis of an oxysterol ligand for the liver x receptor in human macrophages with consequences for cholesterol flux. Arterioscler Thromb Vasc Biol 24:2365–2371

    PubMed  CAS  Google Scholar 

  • Wong J, Quinn CM, Brown AJ (2007a) Synthesis of the oxysterol, 24(S), 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol. Lipids Health Dis 6:10

    PubMed  Google Scholar 

  • Wong J, Quinn CM, Guillemin G, Brown AJ (2007b) Primary human astrocytes produce 24(S),25-epoxycholesterol with implications for brain cholesterol homeostasis. J Neurochem 103:1764–1773

    PubMed  CAS  Google Scholar 

  • Wong J, Quinn CM, Gelissen IC, Brown AJ (2008) Endogenous 24(S),25-epoxycholesterol fine-tunes acute control of cellular cholesterol homeostasis. J Biol Chem 283:700–707

    PubMed  CAS  Google Scholar 

  • Wyles JP, Ridgway ND (2004) VAMP-associated protein-A regulates partitioning of oxysterol-binding protein-related protein-9 between the endoplasmic reticulum and Golgi apparatus. Exp Cell Res 297:533–547

    PubMed  CAS  Google Scholar 

  • Wyles JP, McMaster CR, Ridgway ND (2002) Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum. J Biol Chem 277:29908–29918

    PubMed  CAS  Google Scholar 

  • Wyles JP, Perry RJ, Ridgway ND (2007) Characterization of the sterol-binding domain of oxysterol-binding protein (OSBP)-related protein 4 reveals a novel role in vimentin organization. Exp Cell Res 313:1426–1437

    PubMed  CAS  Google Scholar 

  • Xu Y, Liu Y, Ridgway ND, McMaster CR (2001) Novel members of the human oxysterol-binding protein family bind phospholipids and regulate vesicle transport. J Biol Chem 276:18407–18414

    PubMed  CAS  Google Scholar 

  • Yabe D, Brown MS, Goldstein JL (2002) Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc Natl Acad Sci USA 99:12753–12758

    PubMed  CAS  Google Scholar 

  • Yan D, Olkkonen VM (2008) Characteristics of oxysterol binding proteins. Int Rev Cytol 265:253–285

    PubMed  CAS  Google Scholar 

  • Yan D, Jauhiainen M, Hildebrand RB, van Dijk KW, Van Berkel TJC, Ehnholm C, Van Eck M, Olkkonen VM (2007a) Expression of human OSBP-related protein 1L in macrophages enhances atherosclerotic lesion development in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 27:1618–1624

    PubMed  CAS  Google Scholar 

  • Yan D, Lehto M, Rasilainen L, Metso J, Ehnholm C, Ylä-Herttuala S, Jauhiainen M, Olkkonen VM (2007b) Oxysterol binding protein induces upregulation of SREBP-1c and enhances hepatic lipogenesis. Arterioscler Thromb Vasc Biol 27:1108–1114

    PubMed  CAS  Google Scholar 

  • Yan D, Mäyränpää MI, Wong J, Perttilä J, Lehto M, Jauhiainen M, Kovanen PT, Ehnholm C, Brown AJ, Olkkonen VM (2008) OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages. J Biol Chem 283:332–340

    PubMed  CAS  Google Scholar 

  • Yanagisawa LL, Marchena J, Xie Z, Li X, Poon PP, Singer RA, Johnston GC, Randazzo PA, Bankaitis VA (2002) Activity of specific lipid-regulated ADP ribosylation factor-GTPase-activating proteins is required for Sec14p-dependent Golgi secretory function in yeast. Mol Biol Cell 13:2193–206

    PubMed  CAS  Google Scholar 

  • Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (2002) Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110:489–500

    PubMed  CAS  Google Scholar 

  • Yano T, Inukai M, Isono F (2004) Deletion of OSH3 gene confers resistance against ISP-1 in Saccharomyces cerevisiae. Biochem Biophys Res Commun 315:228–234

    PubMed  CAS  Google Scholar 

  • Yasunobu Y, Hayashi K, Shingu T, Yamagata T, Kajiyama G, Kambe M (2001) Coronary atherosclerosis and oxidative stress as reflected by autoantibodies against oxidized low-density lipoprotein and oxysterols. Atherosclerosis 155:445–453

    PubMed  CAS  Google Scholar 

  • Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS (1993) SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 75:187–197

    PubMed  CAS  Google Scholar 

  • Yoshikawa T, Shimano H, Amemiya-Kudo M, Yahagi N, Hasty AH, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Kimura S, Ishibashi S, Yamada N (2001) Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. Mol Cell Biol 21:2991–3000

    PubMed  CAS  Google Scholar 

  • Zelcer N, Tontonoz P (2006) Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 116:607–614

    PubMed  CAS  Google Scholar 

  • Zeng B, Zhu G (2006) Two distinct oxysterol binding protein-related proteins in the parasitic protist Cryptosporidium parvum (Apicomplexa). Biochem Biophys Res Commun 346:591–399

    PubMed  CAS  Google Scholar 

  • Zerbinatti CV, Cordy JM, Chen C-D, Guillily M, Suon S, Ray WJ, Seabrook GR, Abraham CR, Wolozin B (2008) Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein. Mol Neurodegener 3:5

    PubMed  Google Scholar 

  • Zhou Q, Wasowicz E, Handler B, Fleischer L, Kummerow FA (2000) An excess concentration of oxysterols in the plasma is cytotoxic to cultured endothelial cells. Atherosclerosis 149:191–197

    PubMed  CAS  Google Scholar 

  • Zieden B, Kaminskas A, Kristenson M, Kucinskiene Z, Vessby B, Olsson AG, Diczfalusy U (1999) Increased plasma 7 beta-hydroxycholesterol concentrations in a population with a high risk for cardiovascular disease. Arterioscler Thromb Vasc Biol 19:967–971

    PubMed  CAS  Google Scholar 

  • Zinser E, Sperka-Gottlieb CD, Fasch EV, Kohlwein SD, Paltauf F, Daum G (1991) Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae. J Bacteriol 173:2026–2034

    PubMed  CAS  Google Scholar 

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Acknowledgements

Work in the author’s group is supported by the Academy of Finland (grant 121457), the Sigrid Juselius Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Cultural Foundation, the Magnus Ehrnrooth Foundation, and the European Union FP7 (LipidomicNet, agreement no. 202272).

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  1. Department of Molecular Medicine, National Public Health Institute, Biomedicum, 104, 00251, Helsinki, Finland

    Vesa M. Olkkonen

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Correspondence to Vesa M. Olkkonen .

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    This chapter is dedicated to my parents, Raimo and Riitta Olkkonen

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    Olkkonen, V.M. (2009). Oxysterols and Oxysterol-Binding Proteins in Cellular Lipid Metabolism. In: Ehnholm, C. (eds) Cellular Lipid Metabolism. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00300-4_2

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