Biochemical characterization of the three major subclasses of lipoprotein A-I preparatively isolated from human plasma

Duverger, Nicolas; Rader, Daniel J.; Duchâteau, Philippe; Jc, Fruchart; Castro, Graciela; Hb, Brewer

doi:10.1021/bi00097a014

Cited by 53 publications

(27 citation statements)

References 58 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, small spherical particles containing only apoA-I represent the majority of the LpA-I particles in the plasma of LCAT-deficient patients. These particles are similar in size to those isolated from normal plasma (66) and are catabolized at a rate similar to that of small LpA-I particles in normal subjects. Given their size, lipid, and apolipoprotein composition, these small particles may be important in promoting cholesterol efflux from cells and maintaining effective reverse cholesterol transport in LCAT-deficient patients.…”

Section: Discussionmentioning

confidence: 67%

“…These combined results indicate that there are two major classes of HDL particles in classic LCAT deficiency and Fish-eye disease: large discoidal particles in the HDL2 density range containing apoA-I and apoA-II, and small spherical particles in the small HDL3 to d > 1.21 g/ml range containing apoA-I without apoA-II. The small particles containing only apoA-I resemble small LpA-I particles preparatively isolated from normolipidemic subjects (66). It has been suggested that the HDL isolated from LCAT-deficient patients may represent nascent HDL particles.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

Rader

Ikewaki²,

Duverger³

et al. 1994

J. Clin. Invest.

115

View full text Add to dashboard Cite

Classic (complete) lecithin:cholesterol acyltransferase (LCAT) deficiency and Fish-eye disease (partial LCAT deficiency) are genetic syndromes associated with markedly decreased plasma levels of high density lipoprotein (HDL) cholesterol but not with an increased risk of atherosclerotic cardiovascular disease. We investigated the metabolism of the HDL apolipoproteins (apo) apoA-I and apoA-II in a total of five patients with LCAT deficiency, one with classic LCAT deficiency and four with Fish-eye disease. Plasma levels ofapoA-II were decreased to a proportionately greater extent (23% of normal) than apoA-1

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

Rader

Ikewaki²,

Duverger³

et al. 1994

J. Clin. Invest.

115

View full text Add to dashboard Cite

show abstract

“…Lipoprotein cholesterol profiles were obtained by fast protein liquid chromatography as described (17). This system allows separation of the three major lipoprotein classes; VLDL, low density lipoproteins, and HDL.…”

Section: Methodsmentioning

confidence: 99%

Alterations in Lipoprotein Metabolism in Peroxisome Proliferator-activated Receptor α-deficient Mice

Peters

Hennuyer

Staels

et al. 1997

Journal of Biological Chemistry

405

279

View full text Add to dashboard Cite

The peroxisome proliferator-activated receptor-␣ (PPAR␣) controls gene expression in response to a diverse class of compounds collectively referred to as peroxisome proliferators. Whereas most known peroxisome proliferators are of exogenous origin and include hypolipidemic drugs and other industrial chemicals, several endogenous PPAR␣ activators have been identified such as fatty acids and steroids. The latter finding and the fact that PPAR␣ modulates target genes encoding enzymes involved in lipid metabolism suggest a role for PPAR␣ in lipid metabolism. This was investigated in the PPAR␣-deficient mouse model. Basal levels of total serum cholesterol, high density lipoprotein cholesterol, hepatic apolipoprotein A-I mRNA, and serum apolipoprotein A-I in PPAR␣-deficient mice are significantly higher compared with wild-type controls. Treatment with the fibrate Wy 14,643 decreased apoA-I serum levels and hepatic mRNA levels in wild-type mice, whereas no effect was detected in the PPAR␣-deficient mice. Administration of the fibrate Wy 14,643 to wild-type mice results in marked depression of hepatic apolipoprotein C-III mRNA and serum triglycerides compared with untreated controls. In contrast, PPAR␣-deficient mice were unaffected by Wy 14,643 treatment. These studies demonstrate that PPAR␣ modulates basal levels of serum cholesterol, in particular high density lipoprotein cholesterol, and establish that fibrate-induced modulation in hepatic apolipoprotein A-I, C-III mRNA, and serum triglycerides observed in wild-type mice is mediated by PPAR␣.

show abstract

“…Lecithin-cholesterol acyltransferase (LCAT)' is a 416-amino acid glycoprotein produced mainly by the liver that circulates in the plasma compartment as a functional unit with the cholesteryl ester transfer protein (CETP) and apo AI and apo D primarily in the HDL density range (2,3). LCAT, through its role in the esterification of cholesterol, promotes the packaging of this polar lipid into the core of the HDL particles, maintaining a concentration gradient for the diffusion of free cholesterol from peripheral tissues to HDL.…”

mentioning

confidence: 99%

Expression of human lecithin-cholesterol acyltransferase in transgenic mice. Effect of human apolipoprotein AI and human apolipoprotein all on plasma lipoprotein cholesterol metabolism.

Francone¹,

Gong²,

Ng³

et al. 1995

J. Clin. Invest.

View full text Add to dashboard Cite

IntroductionHuman (Hu) lecithin-cholesterol acyltransferase (LCAT) is a key enzyme in the plasma metabolism of cholesterol. To assess the effects of increased plasma levels of LCAT, four lines of transgenic mice were created expressing a Hu LCAT gene driven by either its natural or the mouse albumin enhancer promoter. Plasma LCAT activity increased from 1. The physiologic substrates for LCAT are nascent and mature HDL. Human (Hu) HDL is very heterogeneous both in particle size (5) and protein composition (6). HDL can be separated into two subpopulations on the basis of protein composition, one containing both apo AI and apo All (LpAI/AHI) and one containing apo AI but no apo All (LpAI). Both are heterogeneous in size (7). The size heterogeneity of Hu HDL distinguishes it from the monodisperse population of HDL particles present in the plasma of mice (8).LCAT is associated with transformation and remodeling of HDL. Plasma from LCAT-deficient patients (10, 11 ) contains small, discoidal HDL particles that probably represent nascent HDL (12). These particles undergo marked changes in composition and morphology when LCAT is added, suggesting an essential role of this enzyme in the biogenesis of circulating HDL.In Plasmid DNA was purified by alkaline hydrolysis (14) followed by two rounds of ultracentrifugation. Genomic DNA fragments were obtained by BamHI/NsiI or AatII/SspI digestion of clones pUCLCATBamNsi and pGEMAlbLCAT, respectively ( Fig. 1), separated from vector sequences by agarose gel electrophoresis, extracted from gels using the Geneclean kit (Bio 101, La Jolla, CA), and dialyzed in injection buffer (10 mM Tris-HCl, 1 mM EDTA, pH 7.4).Creation of transgenic mice. Methods utilized in the creation of transgenic mice have been previously described (15). Fertilized embryos used for the microinjection were derived from matings of inbred FVB mice (Charles River Laboratories, Wilmington, MA). The Hu apo AI and Hu apo All transgenic mice used in these studies have previously been described (16,17). These transgenic lines were created and maintained in the C57BL/6 background. In all the studies involving combinations of Hu apo Al, Hu apo All, and LCAT transgenes, the genetic background of each of the transgenic and control mice was (FVB x C57BL/6) F1 hybrids.Preparation and analysis ofDNA and RNA by Southern and Northern blot. Tail tip DNA from 3-wk-old mice was screened for integration of Hu LCAT gene sequences by PCR. Primers were directed to synthesize the exon 6 of the Hu LCAT gene. Amplification reaction using nontransgenic mouse DNA as a template yielded no amplification products. In some experiments, integration of the full-length genomic construct was detected by Southern blot hybridization. 10 jig genomic DNA was digested overnight with 5 U Pstl/jig DNA, electrophoresed in a 1% agarose gel, and transferred to a nylon membrane (Sigma Chemical Co., S. Louis, MO). DNA was cross-linked to the membranes (Stratagene, La Jolla, CA) and hybridized with a 32P-radiolabeled full-length Hu LCAT cDNA as a pro...

show abstract

Biochemical characterization of the three major subclasses of lipoprotein A-I preparatively isolated from human plasma

Cited by 53 publications

References 58 publications

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

Alterations in Lipoprotein Metabolism in Peroxisome Proliferator-activated Receptor α-deficient Mice

Expression of human lecithin-cholesterol acyltransferase in transgenic mice. Effect of human apolipoprotein AI and human apolipoprotein all on plasma lipoprotein cholesterol metabolism.

Contact Info

Product

Resources

About