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Cellular Lipid Metabolism pp 301–313Cite as

Cellular Cholesterol Transport–Microdomains, Molecular Acceptors and Mechanisms

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Abstract

“Reverse” cholesterol transport (RCT) from peripheral tissues to the liver is believed to play a major role in preventing accumulation of this lipid locally. Lipid-poor (prebeta-migrating) high-density lipoprotein (prebeta-HDL) plays a key and probably rate-limiting role in RCT, even though only a small proportion of the cholesterol content of circulating HDL originates from RCT. Normal RCT is explained here on the basis of a two-compartment recycling model. Prebeta-HDL is lipidated in interstitial fluid and lymph by ATP-dependent lipid transporters. These particles are then passed to the plasma compartment, where they become lipid-filled under the influence of the lecithin:cholesterol acyltransferase (LCAT) reaction without further input from transporters. In atherosclerosis, where activated macrophages are uniquely in contact with plasma, lipid transporters can directly stimulate RCT driven by LCAT.

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References

  • Adorni MP, Zimetti F, Billheimer JT, Wang N, Rader DJ, Phillips MC, Rothblat GH (2007) The roles of different pathways in the release of cholesterol from macrophages. J Lipid Res 48:2453–2462

    Article  PubMed  CAS  Google Scholar 

  • Cao G, Garcia CK, Wyne KL, Scultz RA, Parker KL, Hobbs HH (1997) Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor-1. J Biol Chem 272:33068–33076

    Article  PubMed  CAS  Google Scholar 

  • Capponi AM (2002) Regulation of cholesterol supply for mineralocorticoid biosynthesis. Trends Encrocrin Metab 13:118–121

    Article  CAS  Google Scholar 

  • Cavelier C, Lorenzi I, Rohrer L, von Eckardstein A (2006) Lipid efflux by the ATP-binding cassette transporters ABCA1 and ABCG1. Biochim Biophys Acta 1761:655–666

    PubMed  CAS  Google Scholar 

  • Chau P, Nakamura Y, Fielding CJ, Fielding PE (2006) Mechanism of prebeta HDL formation and activation. Biochemistry 45:3981–3987

    Article  PubMed  CAS  Google Scholar 

  • Chau P, Fielding PE, Fielding CJ (2007) Bone morphogenetic protein-1 (BMP-1) cleaves human proapolipoprotein A1 and regulates its activation for lipid binding. Biochemistry 46:8445–8450

    Article  PubMed  CAS  Google Scholar 

  • Clark SB, Norum KR (1977) The lecithin-cholesterol acyltrasnferase activity of lymph. J Lipid Res 18:293–300

    PubMed  CAS  Google Scholar 

  • Curtiss LK, Bonnet DJ, Rye KA (2000) The conformation of apolipoprotein A-I in high density lipoproteins is influenced by lipid composition and particle size: a surface plasmon resonance study. Biochemistry 39:5712–5721

    Article  PubMed  CAS  Google Scholar 

  • Dietschy JM, Turley SD (2002) Control of cholesterol turnover in the mouse. J Biol Chem 277:3801–3804

    Article  PubMed  CAS  Google Scholar 

  • Fielding CJ, Fielding PE (2001) Cellular cholesterol efflux. Biochim Biophys Acta 1533:175–189

    PubMed  CAS  Google Scholar 

  • Fielding CJ, Fielding PE (2007) Reverse cholesterol transport - new roles for prebeta1-HDL and lecithin:cholesterol acyltransferase. In: Fielding CJ (ed) High density lipoproteins. Wiley-VCH, Weinheim, pp 143–161

    Chapter  Google Scholar 

  • Fielding CJ, Fielding PE (2008) In: Vance D, Vance J(eds) Lipids, lipoproteins and membranes, 5th edn. Elsevier, London, pp 533–553

    Chapter  Google Scholar 

  • Fielding PE, Fielding CJ (1995) Plasma membrane caveolae mediate the efflux of cellular free cholesterol. Biochemistry 34:14288–14292

    Article  PubMed  CAS  Google Scholar 

  • Fielding CJ, Bist A, Fielding PE (1999) Intracellular cholesterol transport in synchronized human skin fibroblasts. Biochemistry 38:2506–2513

    Article  PubMed  CAS  Google Scholar 

  • Fielding PE, Nagao K, Hakamata H, Chimini G, Fielding CJ (2000) A two-step mechanism for free cholesterol and phospholipid efflux from human vascular cells to apolipoprotein A-I. Biochemistry 39:14113–14120

    Article  PubMed  CAS  Google Scholar 

  • Hassan HH, Denis M, Krimbou L, Marcil M, Genest J (2006) Cellular cholesterol homeostasis in vascular endothjelial cells. Can J Cardiol 22:35B–40B

    Article  PubMed  Google Scholar 

  • Hennessy LK, Kunitake ST, Kane JP (1993) Apolipoprotein-AI-containing lipoproteins, with or without apolipoprotein A-II, as progenitors of prebeta high density lipoprotein particles. Biochemistry 32:5759–5765

    Article  PubMed  CAS  Google Scholar 

  • Hill WG, Almasri E, Ruiz WG, Apodaca G, Zeidel ML (2005) Water and solute permeability of rat lung caveolae: high permeabilities explained by acyl chain unsaturation. Am J Physiol Cell Physiol 289:C33–C41

    Article  PubMed  CAS  Google Scholar 

  • Kawano M, Miida T, Fielding CJ, Fielding PE (1993) Quantitation of prebeta-HDL-dependent and nonspecific components of the total efflux of cellular cholesterol and phospholipids. Biochemistry 32:5025–5028

    Article  PubMed  CAS  Google Scholar 

  • Kennedy MA, Barrera GC, Nakamura K, Baldan A, Tarr P, Fishbein MC, Frank J Francone OL, Edwards PA (2005) ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 1:121–131

    Article  PubMed  CAS  Google Scholar 

  • Krimbou L, Marcil M, Genest J (2006) New insights into the biogenesis of human high-density lipoproteins. Curr Opin Lipidol 17:258–267

    Article  PubMed  CAS  Google Scholar 

  • Kujiraoka T, Nanjee MN, Oka T, Ito M, Nagano M, Cooke CJ, Takahashi S, Olszewski WL, Wong JS, Stepanova IP, Hamilton RL, Egashira T, Hattori H, Miller NE (2003) Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP and CETP in plasma and peripheral lymph in humans. Arterioscler Thromb Vasc Biol 23:1653–1659

    Article  PubMed  CAS  Google Scholar 

  • Lee JY, Lanningham-Foster L, Boudyguina EY, Smith TL, Young ER, Colvin PL, Thomas MJ, Parks JS (2004) Prebeta high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice. J Lipid Res 45:716–728

    Article  PubMed  CAS  Google Scholar 

  • Lee-Rueckert M, Vikstedt R, Metso J, Ehnholm C, Kovanen PT, Jauhiainen M (2006) Absence of endogeneous phospholipid transfer protein impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells. J Lipid Res 47:1725–1732

    Article  PubMed  CAS  Google Scholar 

  • Lewis GF, Rader DJ (2005) New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 96:1221–1232

    Article  PubMed  CAS  Google Scholar 

  • Lin YC, Ma C, Hsu WC, Lo HF, Yang VC (2007) Molecular interaction between caveolin-1 and ABCA1 on high density lipoprotein-mediated cholesterol efflux in aortic endothelial cells. Cardiovascular Res 75:575–583

    Article  CAS  Google Scholar 

  • Mendez AJ, Lin G, Wade DP, Lawn RM, Oram JF (2001) Membrane domains distinct from cholesterol/sphingomyelin-rich rafts are involved in the ABCA1-mediated lipid secretory pathway. J Biol Chem 276:3158–3166

    Article  PubMed  CAS  Google Scholar 

  • Mitchell CD, King WC, Applegate KR, Forte T, Glomset JA, Norum KR, Gjone E (1980) Characterization of apolipoprotein E-rich high density lipoproteins in familial lecithin:cholesterol acyltransferase deficiency. J Lipid Res 21:625–634

    PubMed  CAS  Google Scholar 

  • Nakamura Y, Kotite L, Gan Y, Spencer TA, Fielding CJ, Fielding PE (2004) Molecular mechanism of reverse cholesterol transport: reaction of prebeta-migrating high density lipoprotein with plasma lecithin:cholesterol acyltransferase. Biochemistry 43:14811–14820

    Article  PubMed  CAS  Google Scholar 

  • Nanjee MN, Cooke CJ, Olszewski WL, Miller NE (2000) Concentrations of electrophoretic and size subclasses of apolipoprotein AI-containing particles in human peripheral lymph. Arterioscler Thromb Vasc Biol 20:2148–2155

    Article  PubMed  CAS  Google Scholar 

  • Nikkari T, Schreibman PH, Ahrens EH (1975) Isotope kinetics of human skin cholesterol secretion. J Exp Med 141:620–634

    Article  PubMed  CAS  Google Scholar 

  • O’Connell BJ, Denis M, Genest J (2004) Cellular physiology of cholesterol efflux in vascular endothelial cells. Circulation 110:2881–2888

    Article  PubMed  Google Scholar 

  • Oram JF, Wolfbauer G, Vaughan AM, Tang C, Albers JJ (2003) Phospholipid transfer protein interacts with and stabilizes ATP-binding cassette transporter A1 and enhances cholesterol efflux from cells. J Biol Chem 278:52379–52385

    Article  PubMed  CAS  Google Scholar 

  • Ortegren U, Karlsson M, Blazic N, Blomqvist M, Nystrom FH, Gustavsson J, Fredman P, Stralfors P (2004) Lipids and glycosphingolipids in caveolae and surrounding plasma membrane of primary rat adipocytes. Eur J Biochem 271:2028–2036

    Article  PubMed  Google Scholar 

  • Out R, Hoekstra M, Habets K, Meurs I, de Waard V, Hildebrand RB, Wang Y, Chimini G, Kuiper J, Van Berkel TJ, Van Eck M (2008) Combined deletion of macrophage ABCA1 and ABCG1 leads to massive lipid accumulation in tissue macrophages and distinct atherosclerosis at relatively low plasma cholesterol levels. Arterioscler Thromb Vasc Biol 28:258–264

    Article  PubMed  CAS  Google Scholar 

  • Parpal S, Karlsson M, Thorn H, Stralfors P (2001) Cholesterol depletion disrupts caveolae and insulin receptor signaling for metabolic control via insulin receptor substrate-1 but not for mitogen-activated protein kinase control. J Biol Chem 276:9670–9678

    Article  PubMed  CAS  Google Scholar 

  • Rothblat GH, Mahlberg FH, Johnson WJ, Phillips MC (1992) Apolipoproteins, membrane cholesterol domains, and the regulation of cholesterol efflux. J Lipid Res 33:1091–1097

    PubMed  CAS  Google Scholar 

  • Sdrobnik W, Borsukova H, Bottcher A, Pfeiffer A, Liebisch G, Schutz GJ, Schindler H, Schmitz G (2002) Apo AI/ABCA1-dependent and HDL3-mediated lipid efflux from compositionally distinct cholesterol-based microdomains. Traffic 3:268–278

    Article  Google Scholar 

  • Sens P, Turner MS (2004) Theoretical model for the formation of caveolae and similar membrane invaginations. Biophys J 86:2049–2057

    Article  PubMed  CAS  Google Scholar 

  • Singaraja RR, Visscher H, James ER, Chroni A, Coutinho JM, Brunham LR, Kang MH, Zannis VI, Chimini G, Hayden MR (2006) Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitro. Circ Res 99:389–397

    Article  PubMed  CAS  Google Scholar 

  • Sparks DL, Frank PG, Braschi S, Neville TA, Marcel YL (1999) Effect of apolipoprotein A-I lipidation on the formation and function of prebeta- and alpha-migrating LpA-I particles. Biochemistry 38:1727–1735

    Article  PubMed  CAS  Google Scholar 

  • Wang N, Silver DL, Costet P, Tall AR (2000) Specific binding of apo A-I, enhanced cholesterol efflux and altered plasma membrane morphology in cells expressing ABCA1. J Biol Chem 275:33053–33058

    Article  PubMed  CAS  Google Scholar 

  • Wolfrum C, Poy MN, Stoffel M (2005) Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med 11:418–422

    Article  PubMed  CAS  Google Scholar 

  • Zeidan A, Broman J, Hellstrand P, Sward K (2003) Cholesterol dependence of vascular ERK1/2 activation and growth in response to stretch: role of endothelin-1. Arterioscler Thromb Vasc Biol 23:1528–1534

    Article  PubMed  CAS  Google Scholar 

  • Zha X, Gauthier A, Genest J, McPherson R (2003) Secretory vesicular transport from the Golgi is altered during ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux. J Biol Chem 278:10002–10005

    Article  PubMed  CAS  Google Scholar 

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  1. Cardiovascular Research Institute, University of California San Francisco, 4th & Parnassus, 0130, San Francisco, CA, 94143, USA

    Christopher J. Fielding

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    Fielding, C.J. (2009). Cellular Cholesterol Transport–Microdomains, Molecular Acceptors and Mechanisms. In: Ehnholm, C. (eds) Cellular Lipid Metabolism. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00300-4_12

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