Molecular physiology of reverse cholesterol transport.
Journal of Lipid ResearchPublished 1 February 1995Open access
C J Fielding, P E Fielding
Citations1,450
SJR quartileQ1
SJR score1.66
SNIP1.20
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TL;DR
The removal of cholesterol from cells, like its delivery, appears to be specific and well regulated, and RCT can now be understood in molecular terms.
Abstract
Reverse cholesterol transport (RCT) is the pathway by which peripheral cell cholesterol can be returned to the liver for catabolism. Evidence of specific functions for molecular structures within individual plasma lipoprotein species has rapidly accumulated from recent studies using molecular and cellular physiology techniques. The removal of cholesterol from cells, like its delivery, appears to be specific and well regulated. Although further research will be needed, RCT can now be understood in molecular terms.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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Journal of Lipid ResearchMetabolism of apoE-free high density lipoproteins in rat hepatoma cells: evidence for a retroendocytic pathway.
78 Citations1990J G DeLamatre, T. G. Sarphie +2 more
It is concluded that of the HDL apoprotein taken up by the cells, the majority is resecreted by a retroendocytosis pathway, and for the possibility that the endocytotic-retroendocyTosis pathway may be involved in lipid delivery to the cell.
BiochemistryUnique Epitope of Apolipoprotein A-I Expressed in Pre-.beta.-1 High-Density Lipoprotein and Its Role in the Catalyzed Efflux of Cellular Cholesterol
75 Citations1994Phoebe E. Fielding, Mikihiko Kawano +4 more
This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-beta-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species.
AtherosclerosisAn investigation of the role of lecithin: cholesterol acyltransferase and triglyceride-rich lipoproteins in the metabolism of pre-beta high density lipoproteins
72 Citations1991R H Neary, Deepak Bhatnagar +4 more
The findings suggest binding and release of pre-beta HDL by triglyceride-rich lipoproteins depending on the prandial state and production from alpha-HDL through the action of lipases.
Biochemical JournalPurification and characterization of two high-density-lipoprotein-binding proteins from rat and human liver
72 Citations1989Minoru Tozuka, Noel Fidge
Evidence is provided for at least two liver plasma-membrane proteins which bind HDL apolipoproteins, suggesting that protein-protein interaction participates to some degree in the mechanism of HDL recognition by cells.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid MetabolismDifferential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: Functional correlation with lecithin : cholesterol acyltransferase
67 Citations1992Takao Ohta, Rie Nakamura +5 more
The results suggest that (i) the function of LpA-I is closely linked to the LCAT activity while that of Lcithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid is not, and (ii) these mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.
BiochemistryApolipoprotein A-I conformation in discoidal particles: Evidence for alternate structures
66 Citations1993Laura Calabresi, Qiang Meng +2 more
Although the variation in immunoreactivity of the epitopes between various LpA-I was not drastic, significant differences in the calculated ED50 values were observed for a number of antibodies in small versus large particles within each class, indicating that particle size can modulate apoA- I conformation.
BiochemistryStructure-function relationships in human lecithin:cholesterol acyltransferase. Site-directed mutagenesis at serine residues 181 and 216
65 Citations1991Omar L. Francone, Christopher J. Fielding
Sequence comparison with other lipases suggests that serine-216 may be at or near the hinge of a helical flap displaced following substrate binding, which strengthens the structural-functional relationship between LCAT and otherlipases.
Journal of Biological ChemistryThe number of amphipathic alpha-helical segments of apolipoproteins A-I, E, and A-IV determines the size and functional properties of their reconstituted lipoprotein particles.
65 Citations1993Alain M. Jonas, Armin Steinmetz +1 more
The results indicate that the diameters of the largest rHDL particles, containing two apolipoproteins per particle, correlate with the maximum number of putative amphipathic alpha-helical segments in their sequences, and that smaller particles of this class may arise from the removal of one or more alpha- Helical segments from contact with lipid.
Journal of Biological ChemistryStructural and functional domains of apolipoprotein A-I within high density lipoproteins.
64 Citations1993Marguerite B. Dalton, J B Swaney
There is a protease-resistant domain constituted by the first 90 residues of A-I, which, in HDL, contain little of the class of amphipathic helix characteristic of the rest of the molecule and most likely form a structure dominated by protein-protein interactions.
Journal of Lipid ResearchInterconversion of prebeta-migrating lipoproteins containing apolipoprotein A-I and HDL.
63 Citations1990BY Ishida, Deborah Albee +1 more
The two strains, the atherosclerosis-susceptible C57BL/6 and -resistant C3H, displayed a similar elevation and induction of prebeta HDL during a dietary switch from laboratory chow to an atherogenic diet with a transient peak occurring at 7 days even when total HDL in the susceptible strain was greatly reduced.
Proceedings of the National Academy of SciencesEffects of site-directed mutagenesis at residues cysteine-31 and cysteine-184 on lecithin-cholesterol acyltransferase activity.
62 Citations1991Omar L. Francone, C J Fielding
The classical inhibitor of LCAT activity, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), which strongly inhibited the native enzyme, had partial inhibitory activity with mutant enzyme species containing a single -SH residue, while the double mutant was not significantly inhibited by DTNB.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid MetabolismEffects of high-density lipoprotein particles containing apo A-I, with or without apo A-II, on intracellular cholesterol efflux
59 Citations1993Shinichi Oikawa, Armando J. Mendez +3 more
The apo-specific HDL particles Lp A-I and LpA-I/A-II are both effective promoters of cholesterol efflux from fibroblasts and aortic endothelial cells.
Biochemical JournalPurification of an apolipoprotein A binding protein from mouse adipose cells
59 Citations1990Ronald Barbaras, Pascal Puchois +3 more
A protein recognizing apolipoproteins AI, AII and AIV was purified from cultured mouse adipose cells of the Ob17MT18 clonal line and revealed two protein bands that were undetectable in growing Ob17PY cells previously shown not to bind the various Apolipoprotein A and not to undergo cholesterol efflux, whereas they were conspicuous in growth-arrested Ob17 PY cells which have recovered these properties.
Journal of Biological ChemistryLocalization of an apolipoprotein A-I epitope critical for lipoprotein-mediated cholesterol efflux from monocytic cells.
58 Citations1994Carole L. Banka, Audrey S. Black +1 more
An immunochemical approach was employed to evaluate the role of human apolipoprotein (apo) A-I in cellular cholesterol efflux and to test the hypothesis that discrete structural domains of the molecule mediate this function.
BiochemistryIntracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins
57 Citations1990M. Mahmood Hussain, Vassilis I. Zannis
The combined data are consistent with the following intra- and/or extracellular modifications of apoAII: modification of the apOAII which results in the net loss of two positive charges; glycosylation of the modified proapoAII with carbohydrate chains containing sialic acid; and proteolytic removal of the prosegment and cyclization of the N-terminal glutamine.
BiochemistryMechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma
55 Citations1990Takashi Miida, C J Fielding +1 more
It is suggested that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol.
Journal of Biological ChemistryRole of low density lipoprotein receptor-dependent and -independent sites in binding and uptake of chylomicron remnants in rat liver.
54 Citations1988Yasuo Nagata, J Chen +1 more
It is concluded that although binding of chylomicron remnants to liver cell membranes is not dependent on the LDL receptor, their intact uptake by hepatocytes is, and this was true for intact membranes and for solubilized reconstituted membranes and with both a crude membrane fraction as well as with purified sinusoidal membranes.
Journal of Biological ChemistryApolipoprotein A-I domains involved in the activation of lecithin:cholesterol acyltransferase. Importance of the central domain
54 Citations1993Qiang-Hua Meng, Laura Calabresi +2 more
It is proposed that enhancing mAbs act by stabilization of an apoA-I conformation which is not favored in small LpA- I, i.e. by increasing binding of amphipathic helices to lipids and indirectly of the lipids in small particles.
Proceedings of the National Academy of SciencesSynthesis and secretion of wild-type and mutant human plasma cholesteryl ester transfer protein in baculovirus-transfected insect cells: the carboxyl-terminal region is required for both lipoprotein binding and catalysis of transfer.
53 Citations1992Janice Au-Young, C J Fielding
Structural and functional analysis suggests that a conserved neutral lipid-binding sequence may be one important factor in the activity of CETP and possibly in several other proteins of plasma and cellular lipid metabolism.
BiochemistryCholesterol is poorly available for free apolipoprotein-mediated cellular lipid efflux from smooth muscle cells
52 Citations1993Qianqian Li, Akira Komaba +1 more
Free cholesterol of SMC is less available than that of MP for free apolipoprotein-mediated generation of HDLs with cellular lipids, resulting in a high phospholipid:cholesterol ratio.
Journal of Biological ChemistryEvidence for the separation of albumin- and apo A-I-dependent mechanisms of cholesterol efflux from cultured fibroblasts into human plasma.
52 Citations1982Christopher J. Fielding, K Moser
Results indicate that efflux to albumin and to high density lipoprotein in plasma represent independent mechanisms; only the latter is coupled to net transport.
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