Human apolipoprotein C-I accounts for the ability of plasma nigh density lipoproteins to inhibit the cholesteryl ester transfer protein activity

被引:107
作者
Gautier, T
Masson, D
de Barros, JPP
Athias, A
Gambert, P
Aunis, D
Metz-Boutigue, MH
Lagrost, L
机构
[1] Hop Bocage, INSERM U498, Lab Biochim Lipoprot, F-21034 Dijon, France
[2] CNRS, Ctr Neurochim, INSERM U338, Lab Biol Commun Cellulaire, F-67084 Strasbourg, France
关键词
D O I
10.1074/jbc.M007210200
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
The aim of the present study was to identify the protein that accounts for the cholesteryl ester transfer protein (CETP)-inhibitory activity that is specifically associated with human plasma high density lipoproteins (HDL). To this end, human HDL apolipoproteins were fractionated by preparative polyacrylamide gradient gel electrophoresis, and 30 distinct protein fractions with molecular masses ranging from 80 down to 2 kDa were tested for their ability to inhibit CETP activity. One single apolipoprotein fraction was able to completely inhibit CETP activity. The N-terminal sequence of the 6-kDa protein inhibitor matched the N-terminal sequence of human apoC-I, the inhibition was completely blocked by specific anti-apolipoprotein C-I antibodies, and mass spectrometry analysis confirmed the identity of the isolated inhibitor with full-length human apoC-I. Pure apoC-I was able to abolish CETP activity in a concentration-dependent manner and with a high efficiency (IC50 = 100 nmol/liter). The inhibitory potency of total delipidated HDL apolipoproteins completely disappeared after a treatment with anti-apolipoprotein C-I antibodies, and the apoC-I deprivation of native plasma HDL by immunoaffinity chromatography produced a mean 43% rise in cholesteryl ester transfer rates. The main localization of apoC-I in HDL and not in low density lipoprotein in normolipidemic plasma provides further support for the specific property of HDL in inhibiting CETP activity.
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页码:37504 / 37509
页数:6
相关论文
共 46 条
[1]  
BARTER PJ, 1980, J LIPID RES, V21, P238
[2]  
CHEUNG MC, 1984, J BIOL CHEM, V259, P2201
[3]   A peptide from hog plasma that inhibits human cholesteryl ester transfer protein [J].
Cho, KH ;
Lee, JY ;
Choi, MS ;
Cho, JM ;
Lim, JS ;
Park, YB .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1998, 1391 (02) :133-144
[4]   Inhibition of cholesteryl ester transfer protein by apolipoproteins, lipopolysaccharides, and cholesteryl sulfate [J].
Connolly, DT ;
Krul, ES ;
Heuvelman, D ;
Glenn, KC .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1996, 1304 (02) :145-160
[5]   Characterization of antibacterial COOH-terminal proenkephalin-A-derived peptides (PEAP) in infectious fluids -: Importance of enkelytin, the antibacterial PEAP209-237 secreted by stimulated chromaffin cells [J].
Goumon, Y ;
Lugardon, K ;
Kieffer, B ;
Lefèvre, JF ;
Van Dorsselaer, A ;
Aunis, D ;
Metz-Boutigue, MH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (45) :29847-29856
[6]   Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. Relation to atherogenesis susceptibility [J].
Guyard-Dangremont, V ;
Desrumaux, C ;
Gambert, P ;
Lallemant, C ;
Lagrost, L .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 1998, 120 (03) :517-525
[7]  
GUYARDDANGREMONT V, 1994, J LIPID RES, V35, P982
[8]   DIFFERENCES IN PLASMA CHOLESTERYL ESTER TRANSFER ACTIVITY IN 16 VERTEBRATE SPECIES [J].
HA, YC ;
BARTER, PJ .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 1982, 71 (02) :265-269
[9]  
HIGGINS DG, 1992, COMPUT APPL BIOSCI, V8, P189
[10]  
IHM J, 1982, J LIPID RES, V23, P1328