HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 41, 40121-40127, October 10, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/41/40121    most recent M305193200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Witting, S. R. Articles by Davidson, W. S. Search for Related Content PubMed PubMed Citation Articles by Witting, S. R. Articles by Davidson, W. S. Social Bookmarking                      What's this?

Ceramide Enhances Cholesterol Efflux to Apolipoprotein A-I by Increasing the Cell Surface Presence of ATP-binding Cassette Transporter A1^*

Scott R. Witting, J. Nicholas Maiorano and W. Sean Davidson 

From the Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529

It is widely accepted that functional ATP-binding cassette transporter A1 (ABCA1) is critical for the formation of nascent high density lipoprotein particles. However, the cholesterol pool(s) and the cellular signaling processes utilized by the ABCA1-mediated pathway remain unclear. Sphingomyelin maintains a preferential interaction with cholesterol in membranes, and its catabolites, especially ceramide, are potent signaling molecules that could play a role in ABCA1 regulation or function. To study the potential role of ceramide in this process, we treated a variety of cell lines with 20 µM C₂-ceramide and examined apolipoprotein-mediated cholesterol efflux to lipid-free apoA-I. We found that cell lines expressing ABCA1 displayed 2-3-fold increases in cholesterol efflux to apoA-I. Cell lines not expressing ABCA1 were unaffected by ceramide. We further characterized the cholesterol efflux effect in Chinese hamster ovary cells. Ceramide treatment did not cause significant cytotoxicity or apoptosis and did not affect cholesterol efflux to non-apolipoprotein acceptors. Raising endogenous ceramide levels increased cholesterol efflux to apoA-I. Using a cell surface biotinylation method, we found that the total cellular ABCA1 and that at the plasma membrane were increased with ceramide treatment. Also ceramide enhanced the binding of fluorescently labeled apoA-I to Chinese hamster ovary cells. These data suggest that ceramide may increase the plasma membrane content of ABCA1, leading to increased apoA-I binding and cholesterol efflux.

Received for publication, May 17, 2003 , and in revised form, July 22, 2003.

^* This work was supported by NHLBI, National Institutes of Health RO1 Grants HL62542 and HL67093 (to W. S. D.) and a summer student fellowship from the University of Cincinnati Research Counsel (to S. R. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

An Established Investigator of the American Heart Association. To whom correspondence should be addressed: Dept. of Pathology and Laboratory Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0529. Tel.: 513-558-3707; Fax: 513-558-2289; E-mail: Sean.Davidson{at}UC.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. E. Faulkner, S. E. Panagotopulos, J. D. Johnson, L. A. Woollett, D. Y. Hui, S. R. Witting, J. N. Maiorano, and W. S. Davidson An analysis of the role of a retroendocytosis pathway in ABCA1-mediated cholesterol efflux from macrophages J. Lipid Res., June 1, 2008; 49(6): 1322 - 1332. [Abstract] [Full Text] [PDF]

				J. F. Oram The ins and outs of ABCA J. Lipid Res., June 1, 2008; 49(6): 1150 - 1151. [Full Text] [PDF]

				M.-D. Wang, V. Franklin, M. Sundaram, R. S. Kiss, K. Ho, M. Gallant, and Y. L. Marcel Differential Regulation of ATP Binding Cassette Protein A1 Expression and ApoA-I Lipidation by Niemann-Pick Type C1 in Murine Hepatocytes and Macrophages J. Biol. Chem., August 3, 2007; 282(31): 22525 - 22533. [Abstract] [Full Text] [PDF]

				C. Vedhachalam, A. B. Ghering, W. S. Davidson, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips ABCA1-Induced Cell Surface Binding Sites for ApoA-I Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1603 - 1609. [Abstract] [Full Text] [PDF]

				B. Haidar, R. S. Kiss, L. Sarov-Blat, R. Brunet, C. Harder, R. McPherson, and Y. L. Marcel Cathepsin D, a Lysosomal Protease, Regulates ABCA1-mediated Lipid Efflux J. Biol. Chem., December 29, 2006; 281(52): 39971 - 39981. [Abstract] [Full Text] [PDF]

				A. B. Ghering and W. S. Davidson Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I J. Lipid Res., December 1, 2006; 47(12): 2781 - 2788. [Abstract] [Full Text] [PDF]

				A. Kodvawala, A. B. Ghering, W. S. Davidson, and D. Y. Hui Carboxyl Ester Lipase Expression in Macrophages Increases Cholesteryl Ester Accumulation and Promotes Atherosclerosis J. Biol. Chem., November 18, 2005; 280(46): 38592 - 38598. [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]

				J. F. Oram and J. W. Heinecke ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease Physiol Rev, October 1, 2005; 85(4): 1343 - 1372. [Abstract] [Full Text] [PDF]

				R. S. Kiss, J. Maric, and Y. L. Marcel Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux J. Lipid Res., September 1, 2005; 46(9): 1877 - 1887. [Abstract] [Full Text] [PDF]

				L. Krimbou, H. Hajj Hassan, S. Blain, S. Rashid, M. Denis, M. Marcil, and J. Genest Biogenesis and speciation of nascent apoA-I-containing particles in various cell lines J. Lipid Res., August 1, 2005; 46(8): 1668 - 1677. [Abstract] [Full Text] [PDF]

				E. N. Glaros, W. S. Kim, C. M. Quinn, J. Wong, I. Gelissen, W. Jessup, and B. Garner Glycosphingolipid Accumulation Inhibits Cholesterol Efflux via the ABCA1/Apolipoprotein A-I Pathway: 1-PHENYL-2-DECANOYLAMINO-3-MORPHOLINO-1-PROPANOL IS A NOVEL CHOLESTEROL EFFLUX ACCELERATOR J. Biol. Chem., July 1, 2005; 280(26): 24515 - 24523. [Abstract] [Full Text] [PDF]

				W. Le Goff, D.-Q. Peng, M. Settle, G. Brubaker, R. E. Morton, and J. D. Smith Cyclosporin A Traps ABCA1 at the Plasma Membrane and Inhibits ABCA1-Mediated Lipid Efflux to Apolipoprotein A-I Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2155 - 2161. [Abstract] [Full Text] [PDF]

				M. Denis, B. Haidar, M. Marcil, M. Bouvier, L. Krimbou, and J. Genest Characterization of Oligomeric Human ATP Binding Cassette Transporter A1: POTENTIAL IMPLICATIONS FOR DETERMINING THE STRUCTURE OF NASCENT HIGH DENSITY LIPOPROTEIN PARTICLES J. Biol. Chem., October 1, 2004; 279(40): 41529 - 41536. [Abstract] [Full Text] [PDF]

				S. K. Noh and S. I. Koo Milk Sphingomyelin Is More Effective than Egg Sphingomyelin in Inhibiting Intestinal Absorption of Cholesterol and Fat in Rats J. Nutr., October 1, 2004; 134(10): 2611 - 2616. [Abstract] [Full Text] [PDF]

				B. Haidar, M. Denis, M. Marcil, L. Krimbou, and J. Genest Jr. Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter J. Biol. Chem., March 12, 2004; 279(11): 9963 - 9969. [Abstract] [Full Text] [PDF]