Apolipoprotein A-I-containing lipoproteins, with or without apolipoprotein A-II, as progenitors of pre-.beta. high-density lipoprotein particles

Hennessy, Lori K.; Kunitake, Steven T.; Kane, John P.

doi:10.1021/bi00073a006

Cited by 64 publications

(22 citation statements)

References 51 publications

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“…Whereas some investigators (24) have reported that lipid-poor apoA-I is generated when (A-I/A-II)HDL are isolated from human plasma by immunoaffinity chromatography and incubated with CETP and LDL, others (25) have found this not to be the case. This discrepancy highlights the problems that arise when the HDL from human plasma are used to address questions of this type.…”

Section: Discussionmentioning

confidence: 98%

Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

Rye

Wee

Curtiss

et al. 2003

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 98%

Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

Rye

Wee

Curtiss

et al. 2003

Journal of Biological Chemistry

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“…In addition, processes catalyzed by hepatic lipase, CETP and PLTP can generate preβ-HDL from α-HDL particles (48)(49)(50)(51)(52). Furthermore, deficiency of apoM inhibits the formation of preβ-HDL (53;54).…”

Section: Discussionmentioning

confidence: 99%

The Carboxy-Terminal Region of apoA-I Is Required for the ABCA1-Dependent Formation of α-HDL But Not Preβ-HDL Particles in Vivo

et al. 2007

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ABCA1-mediated lipid efflux to lipid poor apoA-I results in the gradual lipidation of apoA-I. This leads to the formation of discoidal HDL which are subsequently converted to spherical HDL by the action of LCAT. We have investigated the effect of point mutations and deletions in the carboxyterminal region of apoA-I on the biogenesis of HDL using adenovirus-mediated gene transfer in apoA-I deficient mice. It was found that the plasma HDL levels were greatly reduced in mice expressing the carboxy-terminal deletion mutants apoA-I [Δ(185-243)] and apoA-I [Δ(220-243)], shown previously to diminish the ABCA1-mediated lipid efflux. The HDL levels were normal in mice expressing the WT apoA-I, the apoA-I[Δ(232-243)] deletion mutant or the apoA-I[E191A/ H193A/K195A] point mutant, which promote normal ABCA1-mediated lipid efflux. Electron microscopy and two-dimensional gel electrophoresis showed that the apoA-I [Δ(185-243)] and apoA-I[Δ(220-243)] mutants formed mainly preβ-HDL particles and few spherical particles enriched in apoE, while WT apoA-I, apoA-I [Δ(232-243)] and apoA-I[E191A/H193A/K195A] formed spherical α-HDL particles. The findings establish that a) deletions that eliminate the 220-231 region of apoA-I prevent the synthesis of α-HDL, but allow the synthesis of preβ-HDL particles in vivo, b) the aminoterminal segment 1-184 of apoA-I can promote synthesis of preβ-HDL type particles in an ABCA1-independent process and c) the charged residues in the 191-195 region of apoA-I do not influence the biogenesis of HDL.Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL), and plays an essential role in the biogenesis, structure, function and plasma concentration of HDL (1-5). ApoA-I contains 22-and 11-amino acid repeats (6;7) which based on earlier x-ray crystallography (8) and computer modeling (7) are organized in amphipathic α-helices. Most recently the lipid-free apoA-I has been crystallized in salt buffers containing 500 μM Cr(III)-Tris-acetylacetonate (Cr-acac3) (9). Under the conditions of crystallization, the protein consists of a four helix amino-terminal bundle and two carboxy-terminal helices.The biogenesis and catabolism of HDL can be considered as a complex pathway that involves several proteins (5). In the early steps of this pathway, apoA-I is secreted mostly lipid-free by Address correspondence to: Angeliki Chroni, Institute of Biology, National Center for Scientific Research "Demokritos", Agia Paraskevi, Athens 15310, Greece; Tel. +30 210 6503626; Fax. +30 210 6511767; Email: achroni@bio.demokritos.gr. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2008 September 3. Published in final edited form as:Biochemistry. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the liver and acquires phospholipid and cholesterol via its interactions with the ATP-binding cassette A1 (ABCA1) lipid transporter (2;10;11). Through a series of intermediate steps that are poorly understood, apoA-I is gradually lipidat...

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“…The depletion in HDL core in vivo might be explained by two distinct mechanisms: either (i) the net transfer of cholesteryl esters from HDL donors toward lipoprotein acceptors without equimolecular net mass transfer of triglycerides in the opposite direction (10), or (ii) the hepatic lipase-catalyzed hydrolysis of HDL triglycerides initially transferred by CETP (7). In both cases, since the amounts of surface components would remain virtually unchanged, the surface-to-core ratio of HDL would progressively increase, and apoA-I excess would finally dissociate from the HDL surface, leading to the generation of a new HDL product of smaller size (41)(42)(43). As observed in the present study in alcoholic patients undergoing a withdrawal therapy, that latter mechanism might promote in vivo mainly the shift of the plasma HDL 2a subfraction toward the small HDL 3b fraction.…”

Section: Table IVmentioning

confidence: 99%

Opposite Effects of Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein on the Size Distribution of Plasma High Density Lipoproteins

Lagrost

Athias

Herbeth

et al. 1996

Journal of Biological Chemistry

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The aim of the present study was to investigate the role of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) in determining the size distribution of high density lipoproteins (HDL) in human plasma. Whereas both purified CETP and PLTP preparations were able to promote the size redistribution of isolated HDL 3 , CETP favored the emergence of small HDL, while PLTP induced the formation of both small and large conversion products. When the total plasma lipoprotein fractions isolated from nine distinct subjects were incubated for 24 h at 37°C with either purified PLTP or purified CETP, significant alterations in the relative proportions of the five distinct plasma HDL subpopulations, i.e., HDL 2b (9.71-12.90 nm), HDL 2a (8.77-9.71 nm), HDL 3a (8.17-8.77 nm), HDL 3b (7.76 -8.17 nm), and HDL 3c (7.21-7.76 nm) were also observed. PLTP induced a significant increase in the relative abundance of HDL 2b (8.66 ؎ 2.34% versus 7.87 ؎ 1.83% in controls; p < 0.01) and a significant decrease in the relative abundance of HDL 3a (32.76 ؎ 3.42% versus 37.87 ؎ 2.62% in controls; p < 0.05). In contrast, CETP significantly reduced the relative proportion of HDL 2a (33.03 ؎ 2.53% versus 37.56 ؎ 6.43% in controls; p < 0.01) but significantly increased the relative proportion of both HDL 3b (21.36 ؎ 6.97% versus 15.58 ؎ 7.75% in controls; p < 0.01) and HDL 3c (3.21 ؎ 4.84% versus 1.13 ؎ 0.56% in controls; p < 0.05). Finally, in order to assess further the physiological relevance of in vitro observations, CETP activity, PLTP activity, and HDL size distribution were determined in plasmas from 33 alcoholic patients entering a cessation program. Alcohol withdrawal was associated with (i) a significant increase in plasma CETP activity (173.5 ؎ 70.5%/h/ml before versus 223.2 ؎ 69.3%/h/ml after alcohol withdrawal, p ‫؍‬ 0.0007), (ii) a significant reduction in plasma PLTP activity (473.9 ؎ 203.7%/h/ml before versus 312.7 ؎ 148.4%/h/ml after alcohol withdrawal, p ‫؍‬ 0. In human plasma, five distinct high density lipoprotein (HDL) 1 subpopulations have been identified on the basis of their apparent diameter as determined by using polyacrylamide gradient gel electrophoresis: HDL 2b (9.71-12.90 nm), HDL 2a (8.77-9.71 nm), HDL 3a (8.17-8.77 nm), HDL 3b (7.76 -8.17 nm), and HDL 3c (7.21-7.76 nm) (1). The heterogeneity of HDL in terms of size distribution may be of physiopathological relevance, and Cheung and coworkers (2) reported significant alterations in HDL size in patients with symptomatic coronary artery disease as compared with healthy control subjects. Interestingly, the presence of coronary artery disease was more strongly associated with abnormalities in HDL particle size distribution than with low HDL cholesterol levels (2). Therefore, these observations raised a considerable interest in identifying the factors that can induce alterations in the relative proportions of plasma HDL 2b , HDL 2a , HDL 3a , HDL 3b , and HDL 3c subfractions in vivo.It is now well established that plasma lipoproteins do ...

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Apolipoprotein A-I-containing lipoproteins, with or without apolipoprotein A-II, as progenitors of pre-.beta. high-density lipoprotein particles

Cited by 64 publications

References 51 publications

Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

The Carboxy-Terminal Region of apoA-I Is Required for the ABCA1-Dependent Formation of α-HDL But Not Preβ-HDL Particles in Vivo

Opposite Effects of Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein on the Size Distribution of Plasma High Density Lipoproteins

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