ABCMdb

PMID: 25522986

Zannis VI, Fotakis P, Koukos G, Kardassis D, Ehnholm C, Jauhiainen M, Chroni A
HDL biogenesis, remodeling, and catabolism.
Handb Exp Pharmacol. 2015;224:53-111. doi: 10.1007/978-3-319-09665-0_2., [PubMed]

Sentences

No. Mutations Sentence Comment

50 ABCA1 p.Trp590Ser A notable exemption is the ABCA1[W590S] mutant which cross-linked stronger to apoA-I than to WT ABCA1 but had diminished capacity to promote cholesterol efflux and to promote formation of HDL (Bodzioch et al. 1999; Fitzgerald et al. 2001, 2002). Login to comment 76 ABCA1 p.Leu222Ala Adenovirus-mediated gene transfer of these mutants in apoA-I / x apoE / mice (Fotakis et al. 2013a, b) showed that compared to the WT apoA-I, the expression of an apoA-I[L218A/L219A/V221A/L222A] mutant decreased plasma cholesterol, apoA-I, and HDL cholesterol levels and generated preb2;- and b1;4 HDL subpopulations (Fotakis et al. 2013a) (Table 1 and Fig. 3a-g). Login to comment 77 ABCA1 p.Leu222Ala To eliminate the involvement of apoE in the generation of apoE-containing HDL particles (Kypreos and Zannis 2007), the apoA-I[L218A/L219A/V221A/L222A] mutant was expressed in apoA-I / x apoE / mice via adenovirus-mediated gene transfer (Fotakis et al. 2013a). Login to comment 81 ABCA1 p.Leu222Ala ABCA1 p.Leu222Ala ABCA1 p.Leu222Ala Table 1 Plasma lipids and hepatic mRNA levels of apoA-I / or apoA-I / x apoE / mice expressing WT and mutant forms of apoA-I in the presence and absence of LCAT as indicated Protein expressed Total cholesterol (mg/dL) Triglycerides (mg/dL) Relative apoA-I mRNA (%) apoA-I plasma levels (mg/dL) WT apoA-I in apoA-I / mice 278 74 78 24 100 26 260 40 apoA-I[L218A/L219A/V221A/ L222A] in apoA-I / mice 45 14 50 20 95 24 41 5 WT apoA-I in apoA-I / x apoE / mice 1,343 104 294 129 100 13 - apoA-I[L218A/L219A/V221A/ L222A] in apoA-I / x apoE / mice 778 52 18 2 92 23 - apoA-I[L218A/L219A/V221A/ L222A] plus LCAT in apoA-I / x apoE / mice 754 122 37 10 90 3 - Fig. 3 (a-g) ApoA-I mutations and their effect on the HDL phenotypes. Login to comment 82 ABCA1 p.Leu222Ala Analysis of plasma of apoA-I / x apoE / mice infected with adenoviruses expressing the WT apoA-I or the apoA-I [L218A/L219A/V221A/L222A] mutant, as indicated, by density gradient ultracentrifugation and SDS-PAGE (a, e). Login to comment 83 ABCA1 p.Leu222Ala EM analysis of HDL fractions 6-7 obtained from apoA-I / x apoE / mice expressing the WT apoA-I or the apoA-I[L218A/L219A/V221A/L222A] mutant, as indicated, following density gradient ultracentrifugation of plasma (b, f). Login to comment 85 ABCA1 p.Leu222Ala Two-dimensional gel electrophoresis of plasma of apoA-I / x apoE / mice infected with adenoviruses expressing WT apoA-I or the apoA-I[L218A/L219A/V221A/L222A] mutant, as indicated (d, g) These particles may originate from apoB-48 containing lipoproteins that are found in the HDL fractions (Fig. 3c). Login to comment 88 ABCA1 p.Leu222Ala Co-expression of the apoA-I[L218A/L219A/V221A/L222A] mutant and human LCAT in apoA-I / x apoE / mice did not correct the plasma apoA-I levels and did not correct the aberrant HDL phenotype. Login to comment 92 ABCA1 p.Leu222Ala The phenotype produced by the apoA-I[L218A/L219A/V221A/L222A] mutations is distinct from all previously described phenotypes and cannot be corrected by overexpression of LCAT. Login to comment 94 ABCA1 p.Leu222Ala Although other interpretations are possible, the in vivo and in vitro data suggest that the interaction of the apoA-I [L218A/L219A/V221A/L222A] mutant with ABCA1 results in defective lipidation of apoA-I that leads to the generation of preb2;-HDL particles that are not a good substrate for LCAT. Login to comment 99 ABCA1 p.Leu222Ala The phenotype generated by the expression of the apoA-I[F225A/V227A/ F229A/L230A] mutant was similar to that obtained with the apoA-I[L218A/ L219A/V221A/L222A] mutant. Login to comment 421 ABCA1 p.Leu222Ala ApoA-I mutants with defective C-terminal apoA-I[Ɗ(185-243)] and apoA-I[L218A/L219A/V221A/ L222A] had 80 % decreased specific binding and 90 % decreased specific transport by aortic endothelial cells. Login to comment