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Y L Marcel

Publications and source records attributed to Y L Marcel.

At least 55 records · Page 3Linked to original sources
PubMed1993

Adipose tissue cholesteryl ester transfer protein mRNA in response to probucol treatment: cholesterol and species dependence.

Probucol treatment results in an increase in plasma concentrations of cholesteryl ester transfer protein (CETP) which may account, in part, for the effects of this agent on plasma concentrations of HDL cholesterol. We have examined the mechanism by which probucol increases plasma CETP and have determined the associated changes in the plasma distribution of high density lipoprotein (HDL) particles. Studies were carried out in nine hypercholesterolemic subjects and five normal volunteers. Probucol treatment resulted in a 31% increase in plasma concentrations of CETP and a 23% decrease in HDL cholesterol (P < 0.01). The plasma concentration of LpA-I decreased by 40% (P < 0.01) whereas no change occurred in the LpA-I/A-II subclass of HDL. Plasma CETP increased significantly by 1 week of therapy and remained stable over 10 to 14 weeks of therapy. In spite of the significant increase in plasma concentrations of CETP, the abundance of CETP mRNA in peripheral adipose tissue decreased markedly (P < 0.001). These results suggested that probucol may alter CETP synthesis in another tissue such as liver or, alternatively, may have other effects on CETP secretion into or catabolism out of the plasma pool. Further studies were carried out in hamsters because, in this species, adipose tissue is a major site and liver is a negligible site for CETP synthesis. Hamsters were fed probucol with or without dietary cholesterol because this species was previously shown to respond to dietary cholesterol with an increase in adipose tissue mRNA levels and in plasma CETP concentrations, thus providing the opportunity to determine whether probucol would alter these parameters independently of the dietary cholesterol effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol.

Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol-induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins. The first two possibilities are studied further in this paper using data on 47 alcohol abusers and 31 control subjects. The activity of CETP was measured as the rate of cholesteryl ester transfer between radio-labeled low density lipoproteins and unlabeled HDL using an in vitro method independent of endogenous plasma lipoproteins. Plasma CETP concentration was determined by a Triton-based radioimmunoassay. The alcohol abusers consuming alcohol (on average 154 g/day) had 28% higher HDL cholesterol (P less than 0.01), 27% lower plasma CETP concentration (P less than 0.001), and 22% lower plasma CETP activity (P less than 0.001) than the controls. Plasma CETP concentration showed a negative correlation with HDL cholesterol among all the subjects (r = -0.317, P less than 0.01) but not among the alcohol abusers alone (r = -0.102, N. S.). During 2 weeks of alcohol withdrawal, plasma CETP concentration and activity of 8 subjects increased, whereas HDL cholesterol decreased by 42% (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Apolipoprotein D transcription occurs specifically in nonproliferating quiescent and senescent fibroblast cultures.

We studied apolipoprotein D (apoD) mRNA in primary cultures of human diploid fibroblasts (HDF). In early-passage HDF no apoD mRNA was detected in replicating cells in sparse culture, but the gene was expressed in quiescent cells in confluent and in serum-starved cultures. In contrast, late-passage HDF expressed apoD mRNA in sparse culture, but the level increased after attainment of confluence. Thus fibroblasts, the common cell-type expressing apoD mRNA in vivo, express this characteristic following growth-arrest. The same pattern of activation was found in another fibroblast cell line deficient in apoB/E (LDL) receptors, excluding a role for cellular cholesterol delivery by the LDL-receptor pathway controlling apoD expression.

Apolipoproteins↗
PubMed1991

Differential effects of lecithin and cholesterol on the immunoreactivity and conformation of apolipoprotein A-I in high density lipoproteins.

Recently identified epitopes in apoA-I define a distinct N-terminal region with a complex tertiary structure, characterized by multiple discontinuous epitopes. Other epitopes are constituted of short domains centered either on beta-turns or random coils or on the 22-mer amphipathic alpha-helices (Marcel, Y. L., Provost, P. R., Koa, H., Raffaï, E., Vu Dac, N., Fruchart, J.-C., and Rassart, E. (1991) J. Biol. Chem. 266, 3644-3653). The compared immunoreactivity of seven epitopes studies here in response first to delipidation of high density lipoprotein (HDL) apoA-I by detergents, and second to modifications of HDL lipid composition by phospholipase A2 or by enrichment in surface lipids demonstrates that apoA-I has a flexible conformation which is readily responsive to the nature and concentration of bound lipids and that the structure of lipid-free apoA-I is significantly different from that of HDL-bound apoA-I, possibly representing a condensed molecule with several masked domains. In HDL apoA-I, these epitopes define five distinct domains which are characterized by particular responses to lipid modifications. However, two domains, each starting at the N-terminal beta-turn of an amphipathic alpha-helical repeat (residues 99-121 and 186-209, respectively) have almost identical immunoreactivity whether after detergent treatment or after changes in cholesterol and phospholipid levels, a property which probably reflects the known periodicity of apoA-I structural 22-mers. The immunoreactivity of a discontinuous epitope, representative of the N-terminal domain, is inversely related to the concentration of phospholipids, a unique characteristic among the epitopes tested here which indicates that the complex N-terminal region interacts with phospholipids, either directly or indirectly. These studies demonstrate that the conformation of multiple domains of HDL apoA-I is dependent on lipid phase composition and differentially affected by cholesterol and phospholipids.

Apolipoprotein A-I↗
PubMed1991

The amphipathic alpha-helical repeats of apolipoprotein A-I are responsible for binding of high density lipoproteins to HepG2 cells.

Nine monoclonal antibodies (mAbs) against apoA-I reacting with distinct but overlapping epitopes covering more than 90% of the sequence have been used to block the interaction of 125I-labeled high density lipoprotein (125I-HDL) with HepG2 cells in order to delineate the cell binding domain of apolipoprotein A-I (apoA-I). While 2 mAbs reacting with epitopes exclusively localized in the N-terminal region (residues 1 to 86) enhanced slightly association of 125I-HDL, all other mAbs, which react with epitopes localized in the regions of amphipathic alpha-helical repeats, inhibited that association by 9 to 15%. Although this inhibition is not significant compared to the effect of an irrelevant mAb, combination of these mAbs could significantly inhibit the association of 125I-HDL (32 to 43%) as could polyclonal antibodies (up to 95%). These results are compatible with the concept of HDL binding to these cells via the nonexclusive interaction of each of the amphipathic alpha-helical repeats of apoA-I. When the same approach was applied to block the association of 3H-cholesteryl ether (CE)-labeled HDL to HepG2 cells, each anti-apoA-I could inhibit by 15 to 25% the cellular association of cholesteryl ether while mAbs in combination or polyclonal antibodies could inhibit this association up to 45% or 60%, respectively. The cholesteryl ether radioactivity that remained associated with the cells (40%) in the presence of polyclonal antibodies could be effectively blocked by addition of an antibody against the receptor binding domain of apoE (1D7). Therefore, the differential cellular association of cholesteryl ether compared to apolipoprotein can be explained by the presence of apoE secreted by HepG2 and apoE or apoB/E receptors. Thus, we conclude that the optimum uptake of both cholesteryl ether and apoA-I of HDL by cells requires the accessibility of the entire apoA-I and the cooperative binding of the amphipathic alpha-helical repeats to HepG2 cell membranes. This type of interaction would explain the competitive binding observed for apoA-I, -A-II, and -A-IV by others.

Antibodies, Monoclonal↗
PubMed1991

Mapping apolipoprotein B on the low density lipoprotein surface by immunoelectron microscopy.

Apolipoprotein B (apoB) was mapped using electron microscopy to visualize pairs of monoclonal antibodies binding to the low density lipoprotein (LDL) surface. The sites at which these monoclonals bind the apoB polypeptide sequence had already been established. The angular distances between all possible pairs of binding sites except one allowed the relative placement of six epitopes on the LDL sphere. We conclude that apoB extends over at least a hemisphere of the LDL surface since four epitopes are located in the Northern Hemisphere at sites arbitrarily designated as the North Pole, the Aleutian Islands, Bogotá, and in the Atlantic Ocean, while two are found in the Southern Hemisphere at Buenos Aires and at Madagascar. ApoB appears to possess a restricted flexibility, since these relative epitope locations show a substantial standard deviation in latitude and longitude. Mapping of additional epitopes may provide an answer to the question of whether apoB circumnavigates the LDL sphere.

Antibodies, Monoclonal↗
PubMed1991

The epitopes of apolipoprotein A-I define distinct structural domains including a mobile middle region.

The definition of epitopes on apoA-I provides evidence for a very dense packing of the peptide chain and supports the proposed supersecondary structure, made of repetitive antiparallel helices. Screening with overlapping synthetic hexapeptides shows that only a few epitopes are continuous and that all continuous contact sequences identified within the epitopes coincide or are contiguous to a putative beta-turn, such as residues 1-8, 48-55, 98-104, 118-123, and 135-140. On the N-terminal half of apoA-I we identified 6 overlapping tertiary discontinuous epitopes, uniquely constituted by amino acids and discontinuous sequences on helical segments that are far apart and which define a particular region with a complex tertiary structure. Among these are the epitopes for antibody 5G6, which reacts with residues 45-51, 83-92, 119-126, and 136-143; for A16, which reacts with 14-19, 23-28, and 60-82; and for r-FC1, which reacts with 1-8, 29-35, 78-83, and 98-121. The very far apart discontinuous sequences included in these epitopes can be explained by the predicted turns and coiled domains, and thus provide evidence for such a tertiary structure. Alternatively, these results could also be explained by intermolecular epitopes involving the N-terminal region. In contrast, in the middle of apoA-I, all identified epitopes are shorter and discontinuous within the secondary structure and are constituted by residues forming a beta-turn with all or part of an adjacent alpha-helix. We hypothesize that these multiple epitopes, that are mostly limited to a single helix, reflect the existence of a very mobile domain, possibly with hinged pairs of adjacent alpha-helices. On the C-terminal half of apoA-I, several monoclonal antibodies react with overlapping epitopes located between residues 149 and 186, which probably reflects 2 antiparallel alpha-helices interrupted by a beta-turn.

Amino Acid Sequence↗
PubMed1991

Apolipoprotein D--an atypical apolipoprotein.

The structure of ApoD and its sites of synthesis have been discovered. These characteristics differ from those of the other apolipoproteins. The role of ApoD in the plasma lipoprotein system remains to be discovered, but the recent, rapid increase in our knowledge of this protein suggests that it plays an important role in the homeostasis or housekeeping of probably all organs. One of its functions is likely to be the transport of a hydrophobic ligand (a lipid) in a one-to-one molar ratio with itself. This transport is likely to occur unidirectionally between neighboring cells in an organ, and between perivascular cells and the blood circulation. The chemical structure of the natural ligand, or ligands, of ApoD in normal cells in vivo or in culture is not known, but ApoD has been shown to bind some steroids and bilirubin. Remarkable upregulation of synthesis of ApoD has been observed during regeneration of injured peripheral nerves. Perhaps the physiologic role of ApoD will prove to be more interesting and of equal importance in biology to the roles of the other apolipoproteins in cardiovascular disease.

Animals↗
PubMed1991

Expression of recombinant human apolipoprotein A-I in Chinese hamster ovary cells and Escherichia coli.

Human recombinant apolipoprotein (apo) A-I was produced by Chinese hamster ovary (CHO) cells and Escherichia coli with expression vectors containing cDNAs encoding preproapoA-I or apoA-I, respectively. The apoA-I from CHO cells was purified from the culture medium by ammonium sulfate precipitation, phenyl-Sepharose chromatography, and affinity purification on anti-apoA-I immunoabsorber. Human apoA-I was produced in E. coli as a fusion protein with glutathione S-transferase. A four amino acid linker, which separated the two proteins, was specifically recognized and cut by Factor Xa. The purification was accomplished by chromatography of E. coli extracts on glutathione-Sepharose and digestion with Factor Xa. The highest production level was found to be 0.5 micrograms/ml of culture medium per 48 h for a clone of stable transformant of CHO cells, whereas E. coli could produce as much as 20 micrograms/ml of bacterial culture. These apoA-I forms were compared in terms of molecular weight, isoelectric point, and expression of several epitopes. Recombinant apoA-I obtained from CHO cells appears intact and its isoelectric point is compatible with that of the mature form and the proform of apoA-I, whereas a part of the apoA-I produced by E. coli does not contain the COOH-terminus. Also, two of six epitopes are expressed to a greater extent in apoA-I obtained from E. coli than in apoA-I obtained from human plasma.

Animals↗
PubMed1991

Cu2(+)-mediated oxidation of dialyzed plasma: effects on low and high density lipoproteins and cholesteryl ester transfer protein.

We previously reported that the expression of an epitope of apolipoprotein B (apoB), mapped to the C-terminus and defined by antibody Bsol7, increased during Cu2(+)-mediated oxidation of isolated low density lipoprotein (LDL). We describe now the properties of Bsol7 as a marker of LDL oxidation in whole plasma in relation to other effects of oxidative treatment of plasma, such as the distribution of apoA-I and cholesteryl ester transfer protein (CETP). In dialyzed plasma, no LDL oxidation was detected at Cu2+ concentrations (5 microM) sufficient for extensive oxidation of isolated LDL. At a higher Cu2+ concentration (50 microM), an increased expression of the Bsol7 epitope was observed; at 250 microM Cu2+, other evidence of LDL oxidation was found. The pattern of LDL response to Cu2+ observed in dialyzed plasma could be reproduced by adding 3% bovine serum albumin to isolated LDL. We demonstrate that the effect of albumin most likely results from its ability to bind copper ions. Incubation of plasma with increasing concentrations of Cu2+ resulted first in the disappearance of alpha 2-migrating HDL, the usual carrier of CEPT; free CETP and high molecular weight apoA-I-containing particles were also generated during oxidation. Addition of oxidized, but not native, LDL to plasma resulted in a transfer to LDL of some of the CETP initially associated with apoA-I. In conclusion, the increased immunoreactivity of the Bsol7 epitope was the most sensitive parameter of LDL oxidation, but other parameters, such as the presence of alpha 2-HDL and CETP-lipoprotein associations were even more sensitive evidence of lipoprotein oxidation.

Apolipoproteins B↗
PubMed1991

Localization of the major sites of rabbit apolipoprotein D gene transcription by in situ hybridization.

We have identified the sites of transcription of the apolipoprotein D (apoD) gene in the rabbit by in situ hybridization. We show here for the first time that 1) apoD mRNA production does not correlate with the sites of steroid hormone production in adrenal glands nor male genital tissues; and 2) the expression of the apoD gene is clearly higher in white than in gray matter throughout the central nervous system (CNS). Specifically, apoD mRNA was abundant near blood vessels and was expressed mostly in fibroblast-like cells, in particular in the testis, the efferent ducts, the ductus epididymis, the lung, and the subarachnoid space of the CNS. Other positive cell types were endothelial cells of adrenal sinusoidal capillaries and glial cells of the CNS. We detected apoD mRNA in both the adrenal cortex and medulla. White but not gray matter showed high levels of apoD mRNA throughout both the rabbit CNS and in human brain. The red pulp of spleen showed a strong hybridization. In prepubertal rabbits apoD mRNA levels were moderate in both testis and epididymis. Epididymal but not testicular expression increased with the onset of puberty and epididymal levels always exceeded those of the testes in animals showing spermatogenesis. Thus, the variation in levels of apoD mRNA among organs in vivo, that we and others have previously reported, can be explained by transcription being not only characteristic of cell type, with a few common cell types producing in each organ, but transcription also varied among cells of the same lineage.

Adrenal Glands↗
PubMed1990

Use of bacterial expression cloning to localize the epitopes for a series of monoclonal antibodies against apolipoprotein B100.

Bacterial expression of apolipoprotein (apo) B cDNA constructs has been used to map a series of monoclonal antibodies (mAbs) to apoB by immunoblotting. In some cases assignments have been confirmed and refined by (i) semipurification of expressed protein, CNBr digestion, and assignment of the immunoreactive fragments; (ii) controlled digestion of the cDNA with the exonuclease Bal31 and bacterial expression of the truncated proteins that result; or (iii) expression of specific segments of cDNA amplified by the polymerase chain reaction. Forty mAbs were mapped to a minimum of 17 separate determinants on apoB. Tryptic fragments have been used to confirm the epitope assignments. In addition, this approach in conjunction with immunoassay, enables some deductions to be made about the trypsin-accessible regions in low density lipoprotein (LDL). The cleavage pattern obtained predicts retention of structure in the cysteine-rich domain of the amino terminus and also in the LDL receptor binding region. Trypsinized LDL was shown to bind to the LDL receptor by an authentic process, using monoclonal antibodies as competing ligands. In conjunction with the previous paper (Milne, R. W., Theolis, R., Maurice, R., Pease, R. J., Weech, P. K., Rassart, E., Fruchart, J.-C., Scott, J., and Marcel, Y. L. (1989) J. Biol. Chem. 265, 19754-19760) the mapped mAbs have been used to define the receptor-binding domain of apoB100 in LDL.

Antibodies, Monoclonal↗
PubMed1990

Distribution and concentration of cholesteryl ester transfer protein in plasma of normolipemic subjects.

A MAb (TP-2) directed against human cholesteryl ester transfer protein (CETP) has been applied to the development of a competitive solid-phase RIA. Experiments with immobilized CETP have shown that upon incubation with plasma or HDL in the presence of Tween (0.05%) apo A-I (but not apo A-II) binds to CETP while TP-2 binding to CETP is concomitantly decreased. With high detergent concentration (0.5% Triton), the interference is eliminated and a specific RIA in which all plasma CETP fractions have the same affinity can be obtained. Plasma levels of CETP, apo A-I, lipids, and lipoproteins were measured in 50 normolipemic, healthy subjects of both sexes. CETP levels varied nearly fourfold with a mean value of 1.7 micrograms/ml. CETP was positively correlated only with apo A-I (r = 0.38) and HDL-triglyceride (r = 0.39). In 29 other normolipemic subjects, where several apolipoproteins were also measured, significant correlations of CETP with apo A-I (0.41), apo E (0.43), and HDL-cholesterol (0.41) were observed, but there was no significant relationship between CETP and either apo A-II, B, or D. In other experiments CETP was shown to be present mostly in HDL3 and VHDL, to display exclusively an alpha 2-electrophoretic migration, and to occur within discrete particles ranging in size from 129 to 154 kD. In conclusion, the association of CETP with apo A-I-containing lipoproteins probably explains the correlation between CETP and apo A-I levels. The relationship between CETP and apo E suggests either a common metabolism or a specific cooperative role in cholesterol ester transport for these proteins.

Adult↗
PubMed1990

Atherogenic diet increases cholesteryl ester transfer protein messenger RNA levels in rabbit liver.

Cholesteryl ester transfer activity is increased in plasma of cholesterol-fed rabbits. To investigate the mechanisms leading to changes in activity, we measured cholesteryl ester transfer protein (CETP) mass by RIA and CETP mRNA abundance by Northern and slot blot analysis using a human CETP cDNA probe in control (n = 8) and cholesterol-fed rabbits (n = 10). Cholesterol feeding (chow plus 0.5% cholesterol, 10% corn oil) for 30 d increased CETP mass in plasma 3.2-fold in the cholesterol-fed rabbits (12.45 +/- 0.82 micrograms/ml) compared with controls (3.86 +/- 0.38 micrograms/ml). In the hypercholesterolemic rabbit, liver CETP mRNA levels were increased 2.8 times control mRNA levels. Actin, apo E, lecithin-cholesterol acyltransferase, and albumin mRNA abundances were unchanged. In contrast to the widespread tissue distribution in humans, CETP mRNA was not detected in extrahepatic tissues of either control or cholesterol-fed animals. Using a sensitive RNase protection assay, the increase in liver CETP mRNA was detectable within 3 d of beginning the high cholesterol diet. Thus, in response to the atherogenic diet there is an early increase in liver CETP mRNA, probably causing increased CETP synthesis and secretion, and increased plasma CETP. The results indicate that the CETP gene may be regulated by diet-induced changes in lipid metabolism.

Actins↗
PubMed1990

Apolipoprotein B-100: immunolocalization and synthesis in human intestinal mucosa.

Despite the evidence that the human small intestine produces two separate species of apoB mRNA encoding for B-100 and B-48, there is a paucity of data concerning the expression of the latter form in this organ. Using a high resolution immunogold approach, with specific polyclonal antibodies and a panel of monoclonal antibodies (2D8, 3A10, 4G3), both forms of apoB (B-48 and B-100) were revealed over enterocytes of pediatric intestinal samples. Intense labeling was observed over microvilli, apical smooth membrane vesicles, multivesicular bodies, the basolateral membrane, as well as the trans Golgi region. Only low labeling was found over the rough endoplasmic reticulum (rER). Similar patterns of apoB distribution characterized both duodenal and jejunal regions. The presence of labeling over the Golgi apparatus and rER suggests a synthetic activity of both forms of apoB by the epithelial cells. To test this hypothesis, human intestine was incubated with [3H]leucine, homogenized, and subjected to immunoprecipitation for apoB. Immunoprecipitates contained radioactivity mainly in apoB-48 with relatively small amounts in apoB-100 when examined by NaDodSO4-polyacrylamide gel electrophoresis. These findings were further supported by the biochemical determination of apoB-100 and apoB-48 in chylomicron particles isolated from thoracic duct lymph of a human donor. Taken together, our data suggest that the human intestine is able to synthesize and to express the apoB-100.

Apolipoprotein B-100↗
PubMed1990

Molecular characterization and differential mRNA tissue distribution of rabbit apolipoprotein D.

We report for the first time the quantification of relative apolipoprotein D (apoD) mRNA concentrations in a wide selection of organs and a detailed characterization of the rabbit protein. ApoD cDNA clones were isolated from a rabbit testis cDNA library by screening with a human apoD cDNA-derived RNA probe. The 912 nucleotide sequence of rabbit apoD cDNA contains a unique reading frame coding for a protein sharing 80% homology with human apoD. The two sequences have two potential asparagine-linked glycosylation sites at the same positions, almost superimposable hydrophobicity plot, and the antigenic proteins show similar charge polymorphism, Mr, and lipoprotein distribution. This high degree of similarity shows that the rabbit system can be used as a model for apoD studies. Moreover, the two consensus sequences of the hydrophobic ligand carrier (alpha 2-microglobulin) family present in human apoD are also found in the rabbit protein and these sequences coincide with the most conserved regions. The distribution of apoD mRNA among rabbit organs was determined by Northern blot and quantitative dot blot analysis. The highest levels of mRNA were found in spleen, adrenal glands, lungs, brain, testis, and kidneys. Moderate or low concentrations were detected in all the other organs tested including liver and small intestine. Thus, our results show that the apoD gene is expressed mainly in peripheral organs, with levels as high as 59-fold that of the liver, unlike other apolipoproteins. We suggest that apoD exerts its main function locally in peripheral organs.

Amino Acid Sequence↗
PubMed1989

The use of monoclonal antibodies to localize the low density lipoprotein receptor-binding domain of apolipoprotein B.

Human apolipoprotein (apo) B-100 is composed of 4536 amino acids. It is thought that the binding of apoB to the low density lipoprotein (LDL) receptor involves an interaction between basic amino acids of the ligand and acidic residues of the receptor. Three alternative models have been proposed to describe this interaction: 1) a single region of apoB is involved in receptor binding; 2) groups of basic amino acids from throughout the apoB primary structure act in concert in apoB receptor binding; and 3) apoB contains multiple independent binding regions. We have found that monoclonal antibodies (Mabs) specific for a region that spans a thrombin cleavage site at apoB residue 3249 (T2/T3 junction) totally blocked LDL binding to the LDL receptor. Mabs specific for epitopes outside this region had either no or partial ability to block LDL binding. In order to define the region of apoB directly involved in the interaction with the LDL receptor we have tested 22 different Mabs for their ability to bind to LDL already fixed to the receptor. A Mab specific for an epitope situated between residues 2835 and 2922 could bind to its epitope on LDL fixed to its receptor whereas a second epitope between residues 2980 and 3084 is inaccessible on receptor-bound LDL. A series of epitopes near residue 3500 of apoB is totally inaccessible, and another situated between residues 4027 and 4081 is poorly accessible on receptor-bound LDL. In contrast, an epitope that is situated between residues 4154 and 4189 is fully exposed. Mabs specific for epitopes upstream and downstream of the region 3000-4000 can bind to receptor-bound LDL with a stoichiometry close to unity. Our results strongly suggest that the unique region of apoB directly involved in the LDL-receptor interaction is that of the T2/T3 junction.

Antibodies, Monoclonal↗