| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 43, 2087-2094, December 2002
Copyright © 2002 by Lipid Research, Inc.
* Cardiovascular Genetics Laboratory, McGill University Health Centre, Royal Victoria Hospital, Montréal, QC H3A 1A1
Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada
1 To whom correspondence should be addressed. e-mail: jacques.genest{at}muhc.mcgill.ca
ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in apoA-I lipidation, a key step in reverse cholesterol transport. cAMP induces apoA-I binding activity and promotes cellular cholesterol efflux. We investigated the role of the cAMP/protein kinase A (PKA) dependent pathway in the regulation of cellular cholesterol efflux. Treatment of normal fibroblasts with 8-bromo-cAMP (8-Br-cAMP) increased significantly apoA-I-mediated cholesterol efflux, with specificity for apoA-I, but not for cyclodextrin. Concomitantly, 8-Br-cAMP increased ABCA1 phosphorylation in a time-dependent manner. Maximum phosphorylation was reached in <10 min, representing a 260% increase compared to basal ABCA1 phosphorylation level. Forskolin, a known cAMP regulator, increased both cellular cholesterol efflux and ABCA1 phosphorylation. In contrast, H-89 PKA inhibitor reduced cellular cholesterol efflux by 70% in a dose-dependent manner and inhibited almost completely ABCA1 phosphorylation. To determine whether naturally occurring mutants of ABCA1 may affect its phosphorylation activity, fibroblasts from subjects with familial HDL deficiency (FHD, heterozygous ABCA1 defect) and Tangier disease (TD, homozygous/compound heterozygous ABCA1 defect) were treated with 8-Br-cAMP or forskolin. Cellular cholesterol efflux and ABCA1 phosphorylation were increased in FHD but not in TD cells.
Taken together, these findings provide evidence for a link between the cAMP/PKA-dependent pathway, ABCA1 phosphorylation, and apoA-I mediated cellular cholesterol efflux.
Abbreviations: ABCA1, ATP-binding cassette transporter A1; CDX, cyclodextrin; CE, cholesteryl ester; CTR, normal control; FC, free cholesterol; FHD, familial HDL deficiency; FRK, forskolin; NBF, nucleotide binding folds; PAGGE, polyacrylamide gradient gel electrophoresis; PKA, protein kinase A; TD, Tangier disease; 8-Br-cAMP, 8-bromo-cAMP
Supplementary key words apolipoprotein A-I • high density lipoprotein • PKA • protein kinase A
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. H. Hassan, M. Denis, D.-Y. D. Lee, I. Iatan, D. Nyholt, I. Ruel, L. Krimbou, and J. Genest Identification of an ABCA1-dependent phospholipid-rich plasma membrane apolipoprotein A-I binding site for nascent HDL formation: implications for current models of HDL biogenesis J. Lipid Res., November 1, 2007; 48(11): 2428 - 2442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, H. Mu, H. Chai, D. Liao, Q. Yao, and C. Chen Human Immunodeficiency Virus Protease Inhibitor Ritonavir Inhibits Cholesterol Efflux from Human Macrophage-Derived Foam Cells Am. J. Pathol., July 1, 2007; 171(1): 304 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Berrougui, M. Isabelle, M. Cloutier, G. Grenier, and A. Khalil Age-related impairment of HDL-mediated cholesterol efflux J. Lipid Res., February 1, 2007; 48(2): 328 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. D. Landry, M. Denis, S. Nandi, S. Bell, A. M. Vaughan, and X. Zha ATP-binding Cassette Transporter A1 Expression Disrupts Raft Membrane Microdomains through Its ATPase-related Functions J. Biol. Chem., November 24, 2006; 281(47): 36091 - 36101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lee-Rueckert, R. Vikstedt, J. Metso, C. Ehnholm, P. T. Kovanen, and M. Jauhiainen Absence of endogenous phospholipid transfer protein impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells J. Lipid Res., August 1, 2006; 47(8): 1725 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-R. Nofer, A. T. Remaley, R. Feuerborn, I. Wolinnska, T. Engel, A. von Eckardstein, and G. Assmann Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter J. Lipid Res., April 1, 2006; 47(4): 794 - 803. [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]
|
|
|
|
 |
|
 W. Le Goff, P. Zheng, G. Brubaker, and J. D. Smith Identification of the cAMP-Responsive Enhancer of the Murine ABCA1 Gene: Requirement for CREB1 and STAT3/4 Elements Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 527 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Maric, R. S. Kiss, V. Franklin, and Y. L. Marcel Intracellular Lipidation of Newly Synthesized Apolipoprotein A-I in Primary Murine Hepatocytes J. Biol. Chem., December 2, 2005; 280(48): 39942 - 39949. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Walter, N. R. Forsyth, W. E. Wright, J. W. Shay, and M. G. Roth The Establishment of Telomerase-immortalized Tangier Disease Cell Lines Indicates the Existence of an Apolipoprotein A-I-inducible but ABCA1-independent Cholesterol Efflux Pathway J. Biol. Chem., May 14, 2004; 279(20): 20866 - 20873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Krimbou, M. Denis, B. Haidar, M. Carrier, M. Marcil, and J. Genest Jr. Molecular interactions between apoE and ABCA1: impact on apoE lipidation J. Lipid Res., May 1, 2004; 45(5): 839 - 848. [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]
|
|
|
|
|
|
S. Suzuki, T. Nishimaki-Mogami, N. Tamehiro, K. Inoue, R. Arakawa, S. Abe-Dohmae, A. R. Tanaka, K. Ueda, and S. Yokoyama Verapamil Increases the Apolipoprotein-Mediated Release of Cellular Cholesterol by Induction of ABCA1 Expression Via Liver X Receptor-Independent Mechanism Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 519 - 525. [Abstract] [Full Text]
|
|
|
|
|
|
M. Denis, B. Haidar, M. Marcil, M. Bouvier, L. Krimbou, and J. Genest Jr. Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1) J. Biol. Chem., February 27, 2004; 279(9): 7384 - 7394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Tang, A. M. Vaughan, and J. F. Oram Janus Kinase 2 Modulates the Apolipoprotein Interactions with ABCA1 Required for Removing Cellular Cholesterol J. Biol. Chem., February 27, 2004; 279(9): 7622 - 7628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Abe-Dohmae, Y. Ikeda, M. Matsuo, M. Hayashi, K.-i. Okuhira, K. Ueda, and S. Yokoyama Human ABCA7 Supports Apolipoprotein-mediated Release of Cellular Cholesterol and Phospholipid to Generate High Density Lipoprotein J. Biol. Chem., January 2, 2004; 279(1): 604 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamauchi, M. Hayashi, S. Abe-Dohmae, and S. Yokoyama Apolipoprotein A-I Activates Protein Kinase C{alpha} Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly J. Biol. Chem., November 28, 2003; 278(48): 47890 - 47897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Witting, J. N. Maiorano, and W. S. Davidson Ceramide Enhances Cholesterol Efflux to Apolipoprotein A-I by Increasing the Cell Surface Presence of ATP-binding Cassette Transporter A1 J. Biol. Chem., October 10, 2003; 278(41): 40121 - 40127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. O. Martinez, B. Agerholm-Larsen, N. Wang, W. Chen, and A. R. Tall Phosphorylation of a Pest Sequence in ABCA1 Promotes Calpain Degradation and Is Reversed by ApoA-I J. Biol. Chem., September 26, 2003; 278(39): 37368 - 37374. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
