Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein

被引:162
作者
Abe-Dohmae, S
Ikeda, Y
Matsuo, M
Hayashi, M
Okuhira, K
Ueda, K
Yokoyama, S [1 ]
机构
[1] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan
[2] Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Lab Cellular Biochem, Kyoto 6068502, Japan
关键词
D O I
10.1074/jbc.M309888200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Apolipoprotein-mediated release of cellular cholesterol and phospholipids was induced in HEK293 cells by expressing human ATP-binding cassette transporter A7 (ABCA7) and ABC transporter A1 (ABCA1) proteins, whether transient or stable, to generate cholesterol-rich high density lipoprotein (HDL). Green fluorescent protein (GFP) attached at their C termini did not influence the lipid release reactions. Transfected ABCA7-GFP induced apolipoprotein-mediated assembly of cholesterol-containing HDL also in L929 cells, which otherwise generate only cholesterol-deficient HDL with their endogenous ABCA1. Time-dependent release of cholesterol and phospholipid by apolipoprotein A ( apoA)-I was parallel both with ABCA1 and with ABCA7 when highly expressed in HEK293 cells, but dose-dependent profiles of lipid release on apoA-I and apoA-II were somewhat different between ABCA1 and ABCA7. Analyses of the stable clones with ABCA1-GFP (293/2c) and ABCA7-GFP (293/6c) by using the same vector indicated some differences in regulation of their activities by protein kinase modulators. Dibutyryl cyclic AMP increased ABCA1-GFP and the release of cholesterol and phospholipid in 293/2c but increased neither ABCA7-GFP nor the lipid release in 293/6c. Expression of ABCA1-GFP- and apoA-I-mediated lipid release were enhanced in parallel by phorbol 12-myristate 13-acetate (PMA) in 293/2c cells. In contrast, the same treatment of 293/6c increased ABCA7-GFP, but apoA-I-mediated lipid release was significantly suppressed. Despite these different responses to PMA, all of the effects of PMA were reversed by a specific protein kinase C inhibitor Go6976, suggesting that the changes were in fact due to protein kinase C activation. A thiol protease inhibitor, N-acetyl-Leu-Leu-norleucinal, increased the protein levels of ABCA1-GFP in 293/2c and ABCA7-GFP in 293/6c, indicating their common degradation pathway. The data indicated that human ABCA7 would compensate the function of ABCA1 for release of cell cholesterol in a certain condition(s), but post-transcriptional regulation of their activity is different.
引用
收藏
页码:604 / 611
页数:8
相关论文
共 37 条
[21]   Transport of lipids from Golgi to plasma membrane is defective in Tangier disease patients and Abc1-deficient mice [J].
Orsó, E ;
Broccardo, C ;
Kaminski, WE ;
Böttcher, A ;
Liebisch, G ;
Drobnik, W ;
Götz, A ;
Chambenoit, O ;
Diederich, W ;
Langmann, T ;
Spruss, T ;
Luciani, MF ;
Rothe, G ;
Lackner, KJ ;
Chimini, G ;
Schmitz, G .
NATURE GENETICS, 2000, 24 (02) :192-196
[22]   Decreased reverse cholesterol transport from Tangier disease fibroblasts - Acceptor specificity and effect of brefeldin on lipid efflux [J].
Remaley, AT ;
Schumacher, UK ;
Stonik, JA ;
Farsi, BD ;
Nazih, H ;
Brewer, HB .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (09) :1813-1821
[23]   Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred [J].
Remaley, AT ;
Rust, S ;
Rosier, M ;
Knapper, C ;
Naudin, L ;
Broccardo, C ;
Peterson, KM ;
Koch, C ;
Arnould, I ;
Prades, C ;
Duverger, N ;
Funke, H ;
Assman, G ;
Dinger, M ;
Dean, M ;
Chimini, G ;
Santamarina-Fojo, S ;
Fredrickson, DS ;
Denefle, P ;
Brewer, HB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12685-12690
[24]   Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1 [J].
Rust, S ;
Rosier, M ;
Funke, H ;
Real, J ;
Amoura, Z ;
Piette, JC ;
Deleuze, JF ;
Brewer, HB ;
Duverger, N ;
Denèfle, P ;
Assmann, G .
NATURE GENETICS, 1999, 22 (04) :352-355
[25]   Complete genomic sequence of the human ABCA1 gene:: Analysis of the human and mouse ATP-binding cassette A promoter [J].
Santamarina-Fojo, S ;
Peterson, K ;
Knapper, C ;
Qiu, Y ;
Freeman, L ;
Cheng, JF ;
Osorio, J ;
Remaley, A ;
Yang, XP ;
Haudenschild, C ;
Prades, C ;
Chimini, G ;
Blackmon, E ;
Francois, T ;
Duverger, N ;
Rubin, EM ;
Rosier, M ;
Denèfle, P ;
Fredrickson, DS ;
Brewer, HB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (14) :7987-7992
[26]   Cloning of rat ABCA7 and its preferential expression in platelets [J].
Sasaki, M ;
Shoji, A ;
Kubo, Y ;
Nada, S ;
Yamaguchi, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 304 (04) :777-782
[27]   Protein kinase a site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux [J].
See, RH ;
Caday-Malcolm, RA ;
Singaraja, RR ;
Zhou, S ;
Silverston, A ;
Huber, MT ;
Moran, J ;
James, ER ;
Janoo, R ;
Savill, JM ;
Rigot, V ;
Zhang, LH ;
Wang, MH ;
Chimini, G ;
Wellington, CL ;
Tafuri, SR ;
Hayden, MR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (44) :41835-41842
[28]   Cyclic AMP induces apolipoprotein E binding activity and promotes cholesterol efflux from a macrophage cell line to apolipoprotein acceptors [J].
Smith, JD ;
Miyata, M ;
Ginsberg, M ;
Grigaux, C ;
Shmookler, E ;
Plump, AS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (48) :30647-30655
[29]  
TAJIMA S, 1983, J BIOL CHEM, V258, P73
[30]   Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjogren's syndrome [J].
Tanaka, AR ;
Ikeda, Y ;
Abe-Dohmae, S ;
Arakawa, R ;
Sadanami, K ;
Kidera, A ;
Nakagawa, S ;
Nagase, T ;
Aoki, R ;
Kioka, N ;
Amachi, T ;
Yokoyama, S ;
Ueda, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 283 (05) :1019-1025