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At least 19 recordsLinked to original sources
PubMed1991

Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent cellular metabolism of human triglyceride-rich lipoproteins through the low density lipoprotein receptor pathway.

The mechanism of inhibition by apolipoprotein C of the uptake and degradation of triglyceride-rich lipoproteins from human plasma via the low density lipoprotein (LDL) receptor pathway was investigated in cultured human skin fibroblasts. Very low density lipoprotein (VLDL) density subfractions and intermediate density lipoprotein (IDL) with or without added exogenous recombinant apolipoprotein E-3 were used. Total and individual (C-I, C-II, C-III-1, and C-III-2) apoC molecules effectively inhibited apoE-3-mediated cell metabolism of the lipoproteins through the LDL receptor, with apoC-I being most effective. When the incubation was carried out with different amounts of exogenous apoE-3 and exogenous apoC, it was shown that the ratio of apoE-3 to apoC determined the uptake and degradation of VLDL. Excess apoE-3 overcame, at least in part, the inhibition by apoC. ApoC, in contrast, did not affect LDL metabolism. Neither apoA-I nor apoA-II, two apoproteins that do not readily associate with VLDL, had any effect on VLDL cell metabolism. The inhibition of VLDL and IDL metabolism cannot be fully explained by interference of association of exogenous apoE-3 with or displacement of endogenous apoE from the lipoproteins. IDL is a lipoprotein that contains both apoB-100 and apoE. By using monoclonal antibodies 4G3 and 1D7, which specifically block cell interaction by apoB-100 and apoE, respectively, it was possible to assess the effects of apoC on either apoprotein. ApoC dramatically depressed the interaction of IDL with the fibroblast receptor through apoE, but had only a moderate effect on apoB-100. The study thus demonstrates that apoC inhibits predominantly the apoE-3-dependent interaction of triglyceride-rich lipoproteins with the LDL receptor in cultured fibroblasts and that the mechanism of inhibition reflects association of apoC with the lipoproteins and specific concentration-dependent effects on apoE-3 at the lipoprotein surface.

Antibodies, Monoclonal↗
PubMed2004

Association of serum apolipoprotein C III levels and apolipoprotein C III gene Sst I polymorphism with carotid intima-media thickness in Chinese type 2 diabetic patients.

Apolipoprotein C III (apo C III) plays a central role in regulating plasma metabolism of triglyceride-rich lipoprotein (TRL). The G3238C allele (Sst I) in the 3'-untranslated region has been found to be associated with raised apo C III levels and hypertriglyceridemia (HTG). Some studies suggest that apo C III and the S(2) allele of apo C III gene are independent risk factors for atherosclerotic diseases. To study the potential association between these factors we analyzed the clinical data and their correlations with serum apo C III levels, apo C III gene Sst I polymorphism, and carotid intima-media thickness (IMT) in 78 unrelated Chinese patients with type 2 diabetes. Apo C III gene Sst I polymorphism was examined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Carotid IMT was measured by color doppler ultrasound examination. Serum apo C III levels were found to be positively associated with plasma TG ( r = 0.527, P < 0.001), TC (r = 0.424, P < 0.001), LDL-C (r = 0.308, P < 0.01) concentrations, and carotid IMT (r =0.359, P < 0.01 ). Multivariate analysis (backward) showed that diastolic blood pressure, apo C III, and fasting insulin levels were independent risk factors of carotid IMT. However, the results did not show the association between S(2) allele and carotid IMT in our diabetic patients. Thus, our study suggested that apo C III is an independent risk factor for atherosclerotic diseases in Chinese type 2 diabetes.

Apolipoprotein C-III↗
PubMed1997

A new fluorometric method for measuring the action of C apolipoproteins on milk lipoprotein lipase.

Monolayer vesicles containing pyrene-labelled nonanoyltriglyceride (1-2 ditetradecyl 3-pyrene nonanoyl glyceride) were used as a substrate to measure bovine milk lipoprotein lipase activity. The activation of lipoprotein lipase by synthetic fragments of apolipoprotein C II and apo C III was measured. Fragments 30-78 and 43-78 had actions similar to that of the entire apo C II. Fragments 50-78 and 55-78 were 50% active, fragment 60-78 was 10% active and fragment 66-78 was inactive. Thus the activating capacity depended on the length of the carboxyterminal fragment. Replacing tyrosine 62 in apo C II by glycine removed all lipoprotein lipase activating capacity, while making Tyr 62 less accessible for binding to lipids and enzyme decreased apo C II activating capacity. Apo C III1 inhibited both basal lipoprotein lipase activity (no apo C II) and lipoprotein lipase activated by apo C II. Apo C III, fragment A (1-40) which did not bind lipids, had no inhibitory effect, while fragment B(41-79) had the same effect as whole apo C III,. Apo AI, AII and C I also inhibited lipoprotein lipase. The fluorometric assay is easy to perform, and suitable for metabolic studies such as fatty-acid exchanges between lipoproteins, as it produces no alteration in the reaction products. It also avoids the use of a radio-labelled substrate.

Animals↗
PubMed1985

Monoclonal antibodies to rat C apolipoproteins: production and characterization of a unique antibody whose binding to apoC-I is inhibited by nonionic detergents.

Four monoclonal antibodies to rat apo (apolipoproteins) C were produced. Three of the monoclonals reacted to apoC-I and one to apoC-III. The IgG monoclonals LRB 21 and LRB 45 recognized a spatially close together or identical apoC-I epitope. The monoclonal LRB 80, however, recognized an epitope that is close to, but distinct from, that recognized by LRB 45 and LRB 21. The antibody LRB 45 recognized an apoC-I epitope that is specific for rat apoC-I, and the antibody did not cross-react with dog or human lipoproteins. Rat apoC-I could be detected in all lipoprotein density fractions, but not in the d greater than 1.21 g/ml fraction. Freezing and thawing of serum did not alter the antibody antigen binding. However, lipolysis of whole serum resulted in a 30% increase in antigenic epitope expression. Antibody antigen reaction could be inhibited by subcritical micellar concentration of nonionic detergents. The inhibition was specific but could be partially reversed if lipid-containing serum was used as a dilution buffer. On feeding animals a diet of olive oil and cholesterol for 2 weeks, apoC-I levels decreased.

Amino Acids↗
PubMed1981

Metabolism of C-apolipoproteins: kinetics of C-II, C-III1 and C-III2, and VLDL-apolipoprotein B in normal and hyperlipoproteinemic subjects.

The turnover and metabolism of the individual C apolipoproteins (C-II, C-III1, and C-III2) were studied following the injection of 125I-labeled VLDL into 15 normal and hyperlipoproteinemic subjects. The C apolipoproteins from very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were separated by analytical isoelectric focusing, and subsequent densitometric scanning and radioassay of the stained bands yielded values for specific activity. In 13 of 15 subjects, kinetics of C-II, C-III1, and C-III2 were best described by a one-pool model, whereas two subjects showed biexponential kinetics. The specific activity-time curves for VLDL and HDL were super-imposable, indicating rapid exchange of all C apolipoproteins in hyperlipidemic as well as in normal subjects. In each subject the half-life was similar for C-II, C-III1, and C-III2, which suggests similar synthesis and catabolic mechanisms for each C apolipoprotein. The mass of exchangeable C-II (range 1.0-5.8 mg/kg), C-III1 (2.6-20 mg/kg), and C-III2 (2.0-13 mg/kg) increased with plasma triglyceride concentrations. Values for flux of C-II were 1.0-2.8 mg/d per kg, for C-III1 1.6-5.6 mg/d per kg, and for C-III2 1.2-3.1 mg/d per kg, but they were not related to levels of plasma triglyceride. However the irreversible fractional catabolic rates were inversely related to C apolipoprotein (and triglyceride) mass, suggesting that expansion in C apolipoprotein pool size is related to slower removal, due to the longer residence time of triglyceride-rich VLDL particles in plasma. This was confirmed by similar findings for B apolipoprotein kinetics in VLDL carried out simultaneously.

Adult↗
PubMed1980

[Relative concentration of VLDL C-apolipoproteins in the hyperlipoproteinaemia of haemodialysis-treated chronic renal failure (author's transl)].

The hypertriglyceridaemia of patients with haemodialysis-treated chronic renal insufficiency was characterized in respect of the apolipoproteins C of VLDL. Using Kane's method, particular attention was paid to the CII/CIII ratio of VLDL isolated by ultracentrifugation in eleven hemodialyzed patients with hypertriglyceridaemia. There was a significant decrease of this ratio compared to twenty three patients with essential hypertriglyceridaemia. A removal defect is suggested as fundamental to the pathogenesis of the hypertriglyceridaemia of renal failure since apoprotein CII acts as a specific activator of lipoprotein lipase.

Humans↗
PubMed1980

Bovine apolipoproteins C. I. Isolation and spectroscopic investigations of the phospholipid binding properties.

Seven low-molecular weight proteins of the C class of apolipoproteins have been isolated from bovine serum high density lipoprotein. Amino acid analysis has shown five of these to be equivalent to the apolipoproteins previously described (Lim, C.T. and Scanu, A.M. (1976) Artery 2, 483-496). A spectroscopic examination of these proteins in the presence of increasing amounts of L-alpha-dimyristoyl phosphatidylcholine single-bilayer vesicles indicates that all bovine apolipoproteins C exhibit changes in secondary and tertiary structure as shown by intrinsic fluorescence intensity, wavelength, and polarization changes, and increases in alpha-helical content as seen by circular dichroism. Evidence is presented to show that bovine apolipoproteins C, like all human apolipoproteins of the A and C classes, can cause phospholipid multilamellar liposomes to disrupt and/or rearrange into a smaller complex which scatters less light. This paper details the screening of the bovine apolipoproteins for their phospholipid binding properties, whereas the following paper will examine the nature of their complexes with phospholipid in more detail. Together, these papers represent the first investigation of protein-lipid interactions involving any nonhuman apolipoproteins C.

Animals↗
PubMed1983

Distribution of C apolipoproteins between the vascular and lymph compartments of the rat.

This study has investigated the kinetics of transfer of C apolipoproteins between the vascular and lymph compartments of the rat. Very-low-density lipoprotein, labeled with [125I]apolipoprotein C, was injected intravenously into lymph duct-cannulated rats and the redistribution of radioactivity between lymph and plasma followed at frequent intervals for 3 h. Equilibration between the two compartments was rapid (10-15 min), and thereafter removal from both compartments continued at similar rates. Specific radioactivity determinations showed that lymph C-III-0, C-III-3, and C-III-2,1 apolipoproteins rapidly reached values identical to those of corresponding plasma C apolipoproteins and the interrelationship between the curves were consistent with precursor-product relationships in which all, or most, of the product (lymph apolipoprotein C-III) was derived from the precursor (plasma). However, the specific radioactivity curves for C-II peptide did not cross; the lower value for lymph C-II apolipoprotein suggests that, unlike C-III apolipoproteins, a substantial proportion (approx. 40%) of lymph C-II peptide is not derived from the plasma compartment. The most likely source of the unlabeled lymph apolipoprotein C-II is synthesis and secretion from the intestine.

Animals↗
PubMed1985

Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver.

Like rat C apolipoproteins, each of the C apolipoproteins from human blood plasma (C-I, C-II, C-III-1, and C-III-2) bound to small chylomicrons from mesenteric lymph of estradiol-treated rats and inhibited their uptake by the isolated perfused rat liver. This inhibitory effect of the C apolipoproteins was independent of apolipoprotein E, which is present only in trace amounts in these chylomicrons. Addition of rat apolipoprotein E to small chylomicrons from mesenteric lymph of normal rats did not displace C apolipoproteins and had no effect on the uptake of these particles by the perfused liver, indicating that an increased ratio of E apolipoproteins to C apolipoproteins on chylomicron particles, unaccompanied by depletion of the latter, may not promote recognition by the chylomicron remnant receptor. The hepatic uptake of remnants of rat hepatic very low density lipoproteins (VLDL) and small chylomicrons, which had been produced in functionally eviscerated rats, was also inhibited by addition of C apolipoproteins. These observations are consistent with the hypothesis that the addition of all of the C apolipoproteins to newly secreted chylomicrons and VLDL inhibits premature uptake of these particles by the liver and that depletion of all of these apolipoproteins from remnant particles facilitates their hepatic uptake. Remnants of chylomicrons and VLDL incubated with rat C apolipoproteins efficiently took up C-III apolipoproteins, but not apolipoprotein C-II (the activator protein for lipoprotein lipase). Preferential loss of apolipoprotein C-II during remnant formation may regulate the termination of triglyceride hydrolysis prior to complete removal of triglycerides from chylomicrons and VLDL.

Animals↗
PubMed1999

Semi-automated rapid isoelectric focusing of apolipoproteins C from human plasma using Phastsystem and immunofixation.

Apolipoproteins (apo) C-I, C-II, and C-III play crucial roles in intravascular lipid metabolism. Whereas apo C-II is an obligate cofactor for lipoprotein lipase, apo C-III was shown to inhibit its action. Apo C-I can be a potent cofactor of human lecithin:cholesterol acyltransferase. Structural mutants and deficiencies of apo C-II lead to hypertriglyceridemia. A similar phenotype is associated with apo C-III mutants and is inducible by overexpression of human apo C-III in transgenic animals. No structural variant has so far been reported for apo C-I. The present paper describes a rapid semi-automated procedure for isoelectric focusing analysis of these C-apolipoproteins from whole plasma or serum and their visualization by immunofixation and silver staining. The procedure allows detection of charged variants of C-apolipoproteins. As applied to 295 patients with coronary heart disease and 85 controls, it also serves to detect deficiency syndromes of these apolipoproteins. The procedure provides reliable, easy and quick analysis of C-apolipoproteins applicable as a routine or screening procedure not restricted to specialized laboratories.

Acrylic Resins↗
PubMed1988

Analysis of human apolipoproteins C by isoelectric focusing in immobilized pH gradients.

Apolipoproteins C are involved in many ways in the metabolism of plasma lipoproteins. Apolipoproteins C from the delipidated VLDL of 35 controls and 165 normo- and hyperlipoproteinemic patients were analyzed by isoelectric focusing on an immobilized pH gradient, pH 4.0-5.0, with 7 M urea, which raised the apparent pH range to 4.8-5.7. This method is an improvement over conventional isoelectric focusing with carrier ampholytes with regard to both resolution and reproducibility. Due to the high resolution (0.1 pH units per cm) additional apolipoprotein C-III bands: C-III0 A1, C-III0 A2, C-III1 C and C-III2 C (the designations A, anodic, and C, cathodic, refer to direction of migration on IEF in relation to the main band) are described for the first time. The possible artifactual nature of these protein bands could be excluded. Cleavage with neuraminidase and peptidases, immunological detection and/or two-dimensional electrophoresis were used to obtain more information. The additional bands seem, in part, to be hydrolysis products of carboxypeptidase A (C-III1 C, C-III2 C). The appearance of C-III1 C and C-III2C was dependent upon the serum triglyceride concentration. The percent distribution of C apolipoproteins in very low density lipoproteins (VLDL) from control serum agreed with previously published data. Apolipoproteins C can also be focused in immobilized pH gradients from VLDL and serum without delipidation.

Apolipoproteins C↗
PubMed1985

The effect of apolipoprotein A on in vitro apolipoprotein C binding and in vivo removal of artificial triacylglycerol-rich particles.

Although the presence of apolipoprotein A on the surface of chylomicrons and its exchange for apolipoprotein C in the mesenteric lymph is known, the functional role of apolipoprotein A in triacylglycerol transport has not been elucidated. Mimicking the in vivo situation, artificial triacylglycerol rich particles (TGRP) with which apolipoprotein AI had been associated, were incubated with high-density lipoproteins (HDL). It was found that apo AI-TGRP bound approximately twice as much apolipoprotein C from HDL as nonprotein-containing TGRP, losing 75% of the apolipoprotein AI originally present. To test whether an increased apolipoprotein C binding in vitro implicated an increased removal rate in vivo, boluses of apolipoprotein AI preincubated and control TGRP were given intravenously (IV) to six hypertriacylglycerolemic patients. The fractional catabolic rate was 35% (range 6% to 65%) higher for apolipoprotein AI preincubated TGRP than for control TGRP. In accordance with the in vitro incubations, the molar ratio of apolipoprotein C to phospholipid on TGRP reisolated 30 minutes after injection was 39% (range 12% to 115%) higher for apo AI triacylglycerol rich particles (TRP) than for control TGRP. The maximal removal capacity of apo AI-TRP, tested in one patient by constant infusion, was increased 53% as compared to control TGRP. Thus, the function of apolipoprotein AI in triacylglycerol transport may be to enhance apolipoprotein C binding to chylomicrons, which are comparable to TRP, and in doing so to enhance their removal from the plasma compartment.

Adult↗
PubMed1979

Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro.

In this study we have determined the fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis of rat plasma very low density lipoprotein (rat VLDL). The experiment was carried out in vitro with lipoprotein lipase purified from bovine milk, VLDL labeled with [(14)C]palmitate, [(3)H]cholesterol, [(32)P]phospholipids, and (125)I-labeled apolipoprotein C and in plasma-devoid systems. Triglyceride hydrolysis ranged between 0 and 98.6%. [(32)P]Phospholipids, unesterified [(3)H]cholesterol, and (125)I-labeled apolipoprotein C were removed from the VLDL (d < 1.019 g/ml) during lipolysis. About one-third of the [(32)P]phosphatidylcholine was hydrolyzed to lysolecithin, and was transferred to the fraction d > 1.21 g/ml. The other two-thirds of the phospholipids were removed unhydrolyzed, mainly to the fraction d 1.04-1.21 g/ml. With the progression of the lipolysis, unesterified [(3)H]cholesterol was removed from VLDL at increasing rates, predominantly to the fraction d 1.04-1.21 g/ml. (125)I-Labeled apolipoprotein C removed from the VLDL partitioned between the fraction of d 1.04-1.21 g/ml and d > 1.21 g/ml. Negative-staining electron microscopy of the fraction d 1.04-1.21 g/ml (containing phospholipids, unesterified cholesterol, and apolipoprotein C) revealed many discoidal lipoproteins. [(3)H]Cholesteryl esters remained associated with the VLDL even when 70-80% of the triglycerides were hydrolyzed. These observations suggest that during in vitro lipolysis of VLDL, surface constituents leave the lipoprotein concomitantly with the hydrolysis of core triglycerides. The process of removal of surface constituents is independent of the presence of an acceptor lipoprotein and may occur in the form of a surface-fragment particle. -Eisenberg, S., and T. Olivecrona. Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro.

Animals↗
PubMed1982

Apolipoprotein C in type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia.

The composition of apolipoprotein C of the very low density lipoproteins (VLDL) was examined in 23 treated Type 2 (non-insulin-dependent) diabetic patients, who had elevated VLDL concentrations. Apolipoprotein C was separated by isoelectric focussing into apolipoprotein C-II which is known as the specific activator of lipoprotein lipase, and three apolipoprotein C-III fragments. A regulatory role has been ascribed to the ratio of apolipoprotein C-II to apolipoprotein C-III in the removal of plasma triglycerides. In our diabetic group, the composition of apolipoprotein C of the VLDL particles was not different from that of a healthy control group. In particular, the above apolipoprotein ratio and the relative amounts of apolipoprotein C-III fragments were normal. Hypertriglyceridaemia in these diabetic subjects does not seem to be related to alterations in the apolipoprotein C composition.

Apolipoprotein C-I↗
PubMed1986

Influence of lysophosphatidylcholine on the C-apolipoprotein content of rat and human triglyceride-rich lipoproteins during triglyceride hydrolysis.

Remnants produced from rat chylomicrons in hepatectomized rats or from human chylomicrons by incubation in postheparin plasma contained much less C-apolipoproteins, but more lysophosphatidylcholine than the parent chylomicrons. A phospholipid-triglyceride emulsion absorbed C-apolipoproteins during incubation in serum, yet not in postheparin plasma, which led to lipid-hydrolysis and increased in lysophosphatidylcholine. The fraction d = 1.006-1.019 g/ml of human serum comprised more lysophosphatidylcholine and less C-apolipoproteins than the fraction d less than 1.006 g/ml. Injection of heparin induced hydrolysis with an increase in lysophosphatidylcholine and loss of C-apolipoproteins in both fractions. These inverse changes of lysophosphatidylcholine and C-apolipoproteins during lipid-hydrolysis suggest a causal relationship, which is strongly supported by the induction of loss of C-apolipoproteins from rat chylomicrons and human triglyceride-rich lipoproteins by addition of lysophosphatidylcholine in vitro. Apolipoprotein C-II was more affected than C-III. These results may elucidate a mechanism for the regulation of the termination of the triglyceride hydrolysis and the final hepatic uptake of remnants.

Animals↗
PubMed1981

Redistribution of apolipoproteins C removed from human very low density lipoprotein during in vitro lipolysis by lipoprotein lipase.

In order to localize the labelled apolipoproteins C removed from Very Low Density Lipoproteins (VLDL) during lipolysis by lipoprotein lipase, we used human VLDL labelled with 125I-labelled apolipoproteins C and employed density gradient ultracentrifugation to analyze lipolytic products. Triacylglycerol hydrolysis occurs when albumin is present even in the absence of serum or High Density Lipoproteins (HDL). In this case, apolipoproteins C were found to be located in several fractions, in different density regions. When either HDL or serum were present in the incubation medium, the removed apolipoproteins C were recovered in only one main fraction in the high density region (1.10 g/ml). Incubations in the presence of either HDL2 or HDL3 gave quite similar results.

Apolipoproteins↗
PubMed2001

Involvement of adenine nucleotide carrier in the mechanism of the apolipoprotein C induced decrease of membrane potential in rat liver mitochondria.

Apolipoprotein C (apo C) was shown to decrease the Ca2+ capacity and membrane potential of mitochondria isolated from rat liver. The specific ligands of adenine nucleotide carrier, ADP and carboxyatractyloside (CAT), inhibited the effect of apo C on the mitochondrial membrane potential. The effect of ADP and CAT was revealed in the absence of Ca2+. We conclude that in the presence of apo C, adenine nucleosides carrier transforms into a pore, and this causes the decrease in the membrane potential of the mitochondria. ADP and CAT support the primary conformation of the carrier and therefore inhibit the effect of apolipoprotein C.

Adenosine Diphosphate↗