Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1813-1821
© 1997 American Heart Association, Inc.
Articles |
Decreased Reverse Cholesterol Transport from Tangier Disease Fibroblasts
Acceptor Specificity and Effect of Brefeldin on Lipid Efflux
From the National Institutes of Health, Clinical Center, Clinical Pathology Department, Bethesda, Maryland (A.T.R.); and National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda, Maryland (U.K.S., J.A.S., B.D.F., H.N., H.B.B.).
Correspondence to: A.T. Remaley, National Institutes of Health, Clinical Center, Clinical Pathology Department, Building 10/2C-431, Bethesda, Maryland 20892.
Abstract Tangier disease is characterized by HDL hypercatabolism and increased deposition of cholesterol in tissues. Tangier disease skin fibroblasts have decreased apoA-I-mediated cholesterol and phospholipid efflux, which may lead to the excess accumulation of cellular cholesterol. The mechanism of apolipoprotein-mediated cholesterol efflux and the apolipoprotein acceptor specificity for cholesterol efflux from normal and Tangier disease fibroblasts was investigated. Normal cells readily effluxed cholesterol and phospholipid to apoA-I and to all of the other apolipoproteins tested (apoA-II, AIV, C-I, C-II, C-III). In contrast, Tangier cells were almost completely defective in cholesterol efflux to apoA-I and to all of the other apolipoproteins tested. HDL was also less effective, by approximately 50%, in stimulating cholesterol efflux from Tangier cells compared with normal cells. In addition, Tangier cells also showed significantly reduced phospholipid efflux to both apolipoproteins and HDL. A similar rate of cholesterol efflux, however, was observed from normal and Tangier cells when phospholipid vesicles or cyclodextrin were used as acceptors. In contrast to normal cells, only phospholipid vesicles and cyclodextrin and not apoA-I or HDL depleted intracellular cholesteryl esters from Tangier cells. Brefeldin, an inhibitor of intracellular vesicular trafficking, decreased HDL-mediated cholesterol efflux by approximately 40% but almost completely blocked both cholesterol and phospholipid efflux to apoA-I from normal cells. Brefeldin also inhibited cholesteryl ester depletion by apoA-I and HDL from normal cells. Brefeldin, however, had no significant effect on cholesterol efflux from Tangier cells to HDL. In summary, Tangier cells were found to be defective in both cholesterol and phospholipid efflux to HDL and apoA-I. The defect in apolipoprotein-mediated lipid efflux was not specific for apoA-I but also occurred for other apolipoproteins, and brefeldin blocked HDL-mediated lipid efflux from normal but not Tangier disease cells. On the basis of these results, a model is proposed whereby decreased cholesterol efflux by apolipoproteins in Tangier cells is the result of a defect in a brefeldin-sensitive pathway of lipid efflux. (Arterioscler Thromb Vasc Biol. 1997;17:1813-1821.)
Key Words: Tangier disease • high-density lipoprotein • cholesterol • atherosclerosis • brefeldin
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M. Marcil, L. Yu, L. Krimbou, B. Boucher, J. F. Oram, J. S. Cohn, and J. Genest Jr Cellular Cholesterol Transport and Efflux in Fibroblasts Are Abnormal in Subjects With Familial HDL Deficiency Arterioscler. Thromb. Vasc. Biol., January 1, 1999; 19(1): 159 - 169. [Abstract] [Full Text] [PDF]
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K. L. Gillotte, W. S. Davidson, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips Removal of cellular cholesterol by pre-ß-HDL involves plasma membrane microsolubilization J. Lipid Res., October 1, 1998; 39(10): 1918 - 1928. [Abstract] [Full Text]
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W. Zhang, B. Asztalos, P. S. Roheim, and L. Wong Characterization of phospholipids in pre-{alpha} HDL: selective phospholipid efflux with apolipoprotein A-I J. Lipid Res., August 1, 1998; 39(8): 1601 - 1607. [Abstract] [Full Text]
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A. von Eckardstein, A. Chirazi, S. Schuler-Lüttmann, M. Walter, J. J. P. Kastelein, J. Geisel, J. T. Real, R. Miccoli, G. Noseda, G. Höbbel, et al. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I J. Lipid Res., May 1, 1998; 39(5): 987 - 998. [Abstract] [Full Text]
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P. Costet, Y. Luo, N. Wang, and A. R. Tall Sterol-dependent Transactivation of the ABC1 Promoter by the Liver X Receptor/Retinoid X Receptor J. Biol. Chem., September 1, 2000; 275(36): 28240 - 28245. [Abstract] [Full Text] [PDF]
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A. E. Bortnick, G. H. Rothblat, G. Stoudt, K. L. Hoppe, L. J. Royer, J. McNeish, and O. L. Francone The Correlation of ATP-binding Cassette 1 mRNA Levels with Cholesterol Efflux from Various Cell Lines J. Biol. Chem., September 8, 2000; 275(37): 28634 - 28640. [Abstract] [Full Text] [PDF]
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W. Chen, D. L. Silver, J. D. Smith, and A. R. Tall Scavenger Receptor-BI Inhibits ATP-binding Cassette Transporter 1- mediated Cholesterol Efflux in Macrophages J. Biol. Chem., September 29, 2000; 275(40): 30794 - 30800. [Abstract] [Full Text] [PDF]
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N. Wang, D. L. Silver, P. Costet, and A. R. Tall Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1 J. Biol. Chem., October 13, 2000; 275(42): 33053 - 33058. [Abstract] [Full Text] [PDF]
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A. J. Mendez, G. Lin, D. P. Wade, R. M. Lawn, and J. F. Oram Membrane Lipid Domains Distinct from Cholesterol/Sphingomyelin-Rich Rafts Are Involved in the ABCA1-mediated Lipid Secretory Pathway J. Biol. Chem., January 26, 2001; 276(5): 3158 - 3166. [Abstract] [Full Text] [PDF]
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M. L. Fitzgerald, A. J. Mendez, K. J. Moore, L. P. Andersson, H. A. Panjeton, and M. W. Freeman ATP-binding Cassette Transporter A1 Contains an NH2-terminal Signal Anchor Sequence That Translocates the Protein's First Hydrophilic Domain to the Exoplasmic Space J. Biol. Chem., April 27, 2001; 276(18): 15137 - 15145. [Abstract] [Full Text] [PDF]
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L. B. Cavelier, Y. Qiu, J. K. Bielicki, V. Afzal, J.-F. Cheng, and E. M. Rubin Regulation and Activity of the Human ABCA1 Gene in Transgenic Mice J. Biol. Chem., May 18, 2001; 276(21): 18046 - 18051. [Abstract] [Full Text] [PDF]
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N. Wang, D. L. Silver, C. Thiele, and A. R. Tall ATP-binding Cassette Transporter A1 (ABCA1) Functions as a Cholesterol Efflux Regulatory Protein J. Biol. Chem., June 22, 2001; 276(26): 23742 - 23747. [Abstract] [Full Text] [PDF]
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E. B. Neufeld, A. T. Remaley, S. J. Demosky, J. A. Stonik, A. M. Cooney, M. Comly, N. K. Dwyer, M. Zhang, J. Blanchette-Mackie, S. Santamarina-Fojo, et al. Cellular Localization and Trafficking of the Human ABCA1 Transporter J. Biol. Chem., July 13, 2001; 276(29): 27584 - 27590. [Abstract] [Full Text] [PDF]
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N. Fournier, A. Cogny, V. Atger, D. Pastier, D. Goudouneche, A. Nicoletti, N. Moatti, J. Chambaz, J.-L. Paul, and A.-D. Kalopissis Opposite Effects of Plasma From Human Apolipoprotein A-II Transgenic Mice on Cholesterol Efflux From J774 Macrophages and Fu5AH Hepatoma Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 638 - 643. [Abstract] [Full Text] [PDF]
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