Article (Scientific journals)
Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A Novel Apolipoprotein C-Iii Variant Ala23thr
Liu, Hq.; Labeur, C.; Xu, Cf. et al.
2000In Journal of Lipid Research, 41 (11), p. 1760-1771
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Abstract :
[en] We have identified a G-to-A transition in exon 3 of the APOC3 gene resulting in a novel Ala23Thr apolipoprotein (apo) C-III variant, associated with apoC-III deficiency in three unrelated Yucatan Indians. The Ala23Thr substitution modifies the hydrophobic/hydrophilic repartition of the helical N-terminal peptide and hence could disturb the lipid association. In vitro expression in Escherichia coli of wild-type and mutant apoC-III enabled the characterization of the variant. Compared with wild-type apoC-III-Ala23, the mutant apoC-III-Thr23 showed reduced affinity for dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles with higher amounts of free apoC-III. Displacement of apoE from discoidal apoE:dipalmitoylphosphatidycholine (DPPC) complex by apoC-III-Thr23 was comparable to wild type but the less efficient binding of the apoC-III-Thr23 to the discoidal complex resulted in a higher apoE/apoC-III (mol/mol) ratio (34%) than with wild-type/apoE:DPPC mixtures. The inhibition of lipoprotein lipase (LPL) by apoC-III-Thr23 was comparable to that of wild type, and therefore effects on LPL activity could not explain the lower triglyceride (Tg) levels in Thr-23 carriers. Thus, these in vitro results suggest that in vivo the less efficient lipid binding of apoC-III-Thr23 might lead to a faster catabolism of free apoC-III, reflected in the reduced plasma apoC-III levels identified in Thr-23 carriers, and poorer competition with apoE, which might enhance clearance of Tg-rich lipoproteins and lower plasma Tg levels seen in Thr-23 carriers.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Liu, Hq.
Labeur, C.
Xu, Cf.
Ferrell, R.
Lins, Laurence  ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Brasseur, Robert ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Rosseneu, M.
Weiss, Km.
Humphries, Se.
Talmud, Pj.
Language :
English
Title :
Characterization Of The Lipid-Binding Properties And Lipoprotein Lipase Inhibition Of A Novel Apolipoprotein C-Iii Variant Ala23thr
Publication date :
2000
Journal title :
Journal of Lipid Research
ISSN :
0022-2275
eISSN :
1539-7262
Publisher :
Lipid Research, United States - Maryland
Volume :
41
Issue :
11
Pages :
1760-1771
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 June 2010

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