2005
DOI: 10.1021/bi050962o
|View full text |Cite
|
Sign up to set email alerts
|

Point Mutations in Apolipoprotein A-I Mimic the Phenotype Observed in Patients with Classical Lecithin:Cholesterol Acyltransferase Deficiency

Abstract: We have analyzed the effect of charged to neutral amino acid substitutions around the kinks flanking helices 4 and 6 of apoA-I and of the deletion of helix 6 on the in vivo activity of LCAT and the biogenesis of HDL. The LCAT activation capacity of apoA-I in vitro was nearly abolished by the helix 6 point (helix 6P-apoA-I[R160V/H162A]) and deletion {helix 6Delta-apoA-I[Delta(144-165)]} mutants, but was reduced to 50% in the helix 4 point mutant (helix 4P-apoA-I[D102A/D103A]). Following adenovirus-mediated gene… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1

Citation Types

1
140
2
1

Year Published

2006
2006
2014
2014

Publication Types

Select...
4
2
1

Relationship

2
5

Authors

Journals

citations
Cited by 39 publications
(144 citation statements)
references
References 68 publications
(105 reference statements)
1
140
2
1
Order By: Relevance
“…The D102A/ D103A and R160V/H162A mutations have been shown to affect functional interactions of rHDL and SR-B1 and thereby affect cholesterol efflux (7). The D102A/D103A, E110A/ E111A, R160V/H162A, and Δ(61-78) mutations affect the LCAT-activation ability of apoA-I (12,31,32). Moreover, the E110A/E111A and Δ(61-78) mutations have been recently shown to affect lipid homeostasis and induce severe hypertriglyceridemia when expressed in A-Ideficient mice (12,32).…”
mentioning
confidence: 99%
“…The D102A/ D103A and R160V/H162A mutations have been shown to affect functional interactions of rHDL and SR-B1 and thereby affect cholesterol efflux (7). The D102A/D103A, E110A/ E111A, R160V/H162A, and Δ(61-78) mutations affect the LCAT-activation ability of apoA-I (12,31,32). Moreover, the E110A/E111A and Δ(61-78) mutations have been recently shown to affect lipid homeostasis and induce severe hypertriglyceridemia when expressed in A-Ideficient mice (12,32).…”
mentioning
confidence: 99%
“…45 Important steps for the maturation of HDL are the esterification of HDL of the nascent particles by Lcat, the transfer of lipids by Pltp, the cholesteryl ester transfer protein and the interaction of the HDL with the HDL receptor (SR-BI) and the ABCG1 lipid transporter. 28,35,45 The fenofibrate treatment significantly downregulated (9.75-fold) the expression of Apoa4 gene. A 10-fold decrease in the Apoa4 gene expression was previously observed in the rat liver by clofibrate treatment.…”
Section: Discussionmentioning
confidence: 95%
“…Plasma lipids, ApoA-I and FPLC profiles Total cholesterol and triglycerides of the plasma and the Fast Protein Liquid Chromatography (FPLC) fractions were determined as described 28 using the WACO (WACO Chemical, Dalton, GA, USA) and INFINITY reagent thermo DNA (Sigma-Aldrich) reagent kits, respectively, according to the manufacturer's instructions. Fractionation of plasma by density gradient ultracentrifugation, electron microscopy of the HDL fractions and non-denaturing two-dimensional gel electrophoresis of plasma was performed as described.…”
Section: Protein Analysismentioning
confidence: 99%
See 2 more Smart Citations