on October 28, 2004
Published online before print October 28, 2004, doi: 10.1161/01.ATV.0000148706.15947.8a
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 14, 2004
Accepted on October 7, 2004
Probucol Inhibits ABCA1-Mediated Cellular Lipid Efflux
Elda Favari ;
From the Departments of Pharmacological and Biological Sciences and Applied Chemistry (E.F., I.Z., F.Z., F.B.) and Clinical Medicine, Nephrology, and Health Sciences (N.R.), University of Parma, Italy; and Gastroenterology and Nutrition (G.H.R.), Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pa.
* To whom correspondence should be addressed. E-mail: fbernini{at}unipr.it.
Objective--ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of lipids from cells to lipid-poor apolipoproteins. In this article, we characterize the effect of this drug on cellular ABCA1-mediated lipid efflux.
Methods and Results--Probucol inhibited cholesterol efflux up to 80% in J774 macrophages expressing ABCA1. In Fu5AH hepatoma cells that contain scavenger receptor class B, type I, but not functional ABCA1, we observed no effect of probucol on cholesterol efflux. Probucol inhibited cholesterol efflux from normal human skin fibroblasts but not from fibroblasts from a Tangier patient. Fluorescent confocal microscopy and biotinylation assay demonstrated that in J774 cells probucol impaired the translocation of ABCA1 from intracellular compartments to the plasma membrane. Probucol also inhibited the formation of an ABCA1-linked cholesterol oxidase sensitive plasma membrane domain. Consistent with the inhibitory effect on ABCA1 translocation to the plasma membrane, probucol reduced cell surface-specific [125I]-labeled apolipoprotein-AI binding.
Conclusions--We conclude that probucol is an effective inhibitor of ABCA1-mediated cholesterol efflux without influencing scavenger receptor class B type I-mediated efflux. The inhibition of ABCA1 translocation to the plasma membrane may in part explain the reported in vivo high-density lipoprotein-lowering action of probucol.
Key words: probucol • lipid efflux • ABCA1 • macrophages • fibroblasts
This article has been cited by other articles:
 |
|
 |
|
  R. Arakawa, M. Tsujita, N. Iwamoto, C. Ito-Ohsumi, R. Lu, C.-A. Wu, K. Shimizu, T. Aotsuka, H. Kanazawa, S. Abe-Dohmae, et al. Pharmacological inhibition of ABCA1 degradation increases HDL biogenesis and exhibits antiatherogenesis J. Lipid Res., November 1, 2009; 50(11): 2299 - 2305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tanigawa, J. T. Billheimer, J.-i. Tohyama, I. V. Fuki, D. S. Ng, G. H. Rothblat, and D. J. Rader Lecithin: Cholesterol Acyltransferase Expression Has Minimal Effects on Macrophage Reverse Cholesterol Transport In Vivo Circulation, July 14, 2009; 120(2): 160 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Weibel, M. R. Joshi, E. T. Alexander, P. Zhu, I. A. Blair, and G. H. Rothblat Overexpression of Human 15(S)-Lipoxygenase-1 in RAW Macrophages Leads to Increased Cholesterol Mobilization and Reverse Cholesterol Transport Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 837 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stefulj, U. Panzenboeck, T. Becker, B. Hirschmugl, C. Schweinzer, I. Lang, G. Marsche, A. Sadjak, U. Lang, G. Desoye, et al. Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1 Circ. Res., March 13, 2009; 104(5): 600 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Delvecchio, P. Bilan, P. Nair, and J. P. Capone LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1 Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L949 - L957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Hassan, D. Bailey, D.-Y. D. Lee, I. Iatan, A. Hafiane, I. Ruel, L. Krimbou, and J. Genest Quantitative Analysis of ABCA1-dependent Compartmentalization and Trafficking of Apolipoprotein A-I: IMPLICATIONS FOR DETERMINING CELLULAR KINETICS OF NASCENT HIGH DENSITY LIPOPROTEIN BIOGENESIS J. Biol. Chem., April 25, 2008; 283(17): 11164 - 11175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Bates, J.-Q. Tao, K. J. Yu, Z. Borok, E. D. Crandall, H. L. Collins, and G. H. Rothblat Expression and Biological Activity of ABCA1 in Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 283 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Adorni, F. Zimetti, J. T. Billheimer, N. Wang, D. J. Rader, M. C. Phillips, and G. H. Rothblat The roles of different pathways in the release of cholesterol from macrophages J. Lipid Res., November 1, 2007; 48(11): 2453 - 2462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Favari, M. Gomaraschi, I. Zanotti, F. Bernini, M. Lee-Rueckert, P. T. Kovanen, C. R. Sirtori, G. Franceschini, and L. Calabresi A Unique Protease-sensitive High Density Lipoprotein Particle Containing the Apolipoprotein A-IMilano Dimer Effectively Promotes ATP-binding Cassette A1-mediated Cell Cholesterol Efflux J. Biol. Chem., February 23, 2007; 282(8): 5125 - 5132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Zanotti, F. Poti, E. Favari, K. R. Steffensen, J.-A. Gustafsson, and F. Bernini Pitavastatin Effect on ATP Binding Cassette A1-Mediated Lipid Efflux from Macrophages: Evidence for Liver X Receptor (LXR)-Dependent and LXR-Independent Mechanisms of Activation by cAMP J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 395 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zimetti, G. K. Weibel, M. Duong, and G. H. Rothblat Measurement of cholesterol bidirectional flux between cells and lipoproteins J. Lipid Res., March 1, 2006; 47(3): 605 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yokoyama Assembly of High-Density Lipoprotein Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 20 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xia, M. Hou, H. Zhu, J. Ma, Z. Tang, Q. Wang, Y. Li, D. Chi, X. Yu, T. Zhao, et al. Anthocyanins Induce Cholesterol Efflux from Mouse Peritoneal Macrophages: THE ROLE OF THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {gamma}-LIVER X RECEPTOR {alpha}-ABCA1 PATHWAY J. Biol. Chem., November 4, 2005; 280(44): 36792 - 36801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Hirano, C. Ikegami, K.-i. Tsujii, Z. Zhang, F. Matsuura, Y. Nakagawa-Toyama, M. Koseki, D. Masuda, T. Maruyama, I. Shimomura, et al. Probucol Enhances the Expression of Human Hepatic Scavenger Receptor Class B Type I, Possibly Through a Species-Specific Mechanism Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2422 - 2427. [Abstract] [Full Text] [PDF]
|
|