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At least 631 records · Page 35Linked to original sources
PubMed2002

High-density lipoprotein-facilitated entry of thyroid hormones into cells: a mechanism different from the low-density lipoprotein-facilitated entry.

In human skin fibroblasts incubated with interstitial fluid concentrations of low-density lipoproteins (LDL) (22 microg/mL) that had been preincubated with [(125)I] thyroid hormone (TH), thyroxine (T(4)) whole-cell saturable up-take (CSU) is approximately 40% greater than in control fibroblasts. This effect of the LDL, which requires upregulation of low-density lipoprotein-receptors (LDL-R; K(d) approximately 20 microg/mL), is less for [(125)I]triiodothyronine (T(3)). We have evaluated high-density lipoproteins (HDL), and assessed whether lipoproteins target TH to the nucleus. In some experiments, fibroblasts were cholesterol-deprived (chol(-)) or cholesterol-enriched (chol(+)) to upregulate LDL-R or high-density lipoprotein-receptors (HDL-R), respectively. In chol(-) fibroblasts, 25 microg/mL of LDL increased both T(4) CSU and T(4) nuclear saturable uptake (NSU) by 48% or 30%, respectively; the latter becoming appreciable at approximately 180 minutes. Interstitial fluid concentrations of HDL (280 microg/mL or approximately 50-fold greater than K(d) of the HDL-R) inhibited both T(4) and T(3) CSU even in chol(+) fibroblasts. However, when chol(+) fibroblasts were incubated first with HDL, and after cell washings with [(125)I]T(4) or [(125)I]T(3), T(4) or T(3) CSU increased by 24% or 12%, respectively. The corresponding increase in chol(-) fibroblasts was 8% or 0%, and in nonmanipulated fibroblasts was 15% or 4%. Unlike LDL, the magnitude of the increase in T(4) or T(3) NSU caused by HDL matched the corresponding CSU, and was already evident at 30 minutes. In conclusion, cells have a LDL-facilitated, LDL-R-mediated mode of entry of TH (T(4) >> T(3)) that targets relatively late only part of TH to the nucleus, and an HDL-facilitated mode of entry (T(4) > T(3)) that targets immediately to the nucleus all of the TH, suggesting entry of TH in free form. This effect of HDL represents facilitated diffusion of TH through the cell membrane.

Cell Nucleus↗
PubMed1987

Lipoprotein lipases, lipoproteins and tissue lipids in rats fed fish oil or coconut oil.

The effect of fish oil and coconut oil on plasma lipoproteins and lipoprotein-catabolizing enzymes [lipoprotein lipase (LPL) and hepatic endothelial lipase (HL)] was studied in rats. Male rats were fed for 4 wk purified diets containing equienergetic, amounts of either coconut oil (group A), coconut oil:fish oil, 50:50 (group B) or fish oil (group C). Whole plasma triacylglycerol, cholesterol and phospholipid concentrations were appreciably lower in group C than in group A, mainly due to a fall in very low density lipoprotein (VLDL) and subgroup 2 of high density lipoprotein (HDL2), with less consistent changes in LDL and HDL3. VLDL components of group B were also considerably lower than corresponding ones in group A. LPL and HL activities were about 50% lower in groups B and C than in group A. Increased hepatic triacylglycerol and cholesterol concentrations were observed in groups B and C. It is suggested that the decrease in LPL and HL activity of fish oil-fed rats may be an adaptive response to the low concentration of the substrate (triacylglycerols) for these enzymes.

Animals↗
PubMed1992

Dietary fish protein modulates high density lipoprotein cholesterol and lipoprotein lipase activity in rabbits.

To explore the pathways by which fish protein feeding influences HDL metabolism, postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured in rabbits fed fish protein or soybean protein combined with corn oil or coconut oil in a 2 x 2 factorial arrangement. In addition to greater serum total and LDL-cholesterol concentrations, the elevated HDL cholesterol concentration caused by feeding fish protein, compared with soybean protein, was accompanied by lower VLDL triglycerides and parallel higher lipoprotein lipase activity in fish protein-fed rabbits. These results suggest an enhanced assembly of circulating HDL through promoted lipoprotein lipase activity in rabbits fed fish protein. Moreover, dietary proteins and lipids interacted with one another to alter HDL triglycerides and liver cholesterol concentrations. Diet-induced changes in lipoprotein lipase activity were, however, not related to insulinemia, which was unaltered by purified diet feeding. The present results suggest that fish protein may affect HDL metabolism through the modulation of lipoprotein lipase activity in rabbits.

Animals↗
PubMed1995

New aspects of risk factors for the development of atherosclerosis, including small low-density lipoprotein, homocyst(e)ine, and lipoprotein(a).

The risk factors for coronary artery disease have been expanded in recent years to include several clinically significant metabolic disorders. The small, dense low-density lipoprotein trait is one of the most common inherited coronary artery disease risk factors and recent reports describe the clinical use of low-density lipoprotein phenotyping for coronary artery disease risk determination, and for treatment in patients with established disease. Apolipoprotein E isoforms play a role in diet responsiveness and may explain approximately 12% of cases of myocardial infarction. Hypoalphalipoproteinemia appears to be a spectrum of overlapping disorders and is difficult to treat. Low-density lipoprotein oxidation may be affected by dietary sources of oxidized fat, and a recent antioxidation trial reported negative results. In the past year, homocyst(e)inemia was reported to play a significant role in coronary artery disease risk prediction and lipoprotein(a) phenotypes appear to clarify the risk of lipoprotein(a).

Coronary Artery Disease↗
PubMed1990

Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia.

Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment.

Apolipoproteins↗
PubMed1987

The interaction of lipolysis products of very low density lipoprotein with plasma high density lipoprotein (HDL): perfusate HDL with plasma HDL subfractions.

The nature of the interaction of high density lipoproteins (HDL), formed during lipolysis of human very low density lipoprotein (VLDL) by perfused rat heart, with subfractions of human plasma HDL was investigated. Perfusate HDL, containing apoliproproteins (apo) E, C-II, and C-III but no apo A-I or A-II, was incubated with a subfraction of HDL (HDL-A) containing apo A-I and A-II, but devoid of apo C-II, C-III, and E. The products of the incubation were resolved by heparin-Sepharose or hydroxylapatite chromatography under conditions which allowed the resolution of the initial HDL-A and perfusate HDL. The fractions were analyzed for apolipoprotein content and lipid composition and assessed for particle size by electron microscopy. Following the incubation, the apo-E-containing lipoproteins were distinct from perfusate HDL since they contained apo A-I as a major component and apo C-II and C-III in reduced proportions. However, the HDL-A fraction contained apo C-II and C-III as major constituents. Associated with these changes in apolipoprotein composition, the apo-E-rich lipoproteins acquired cholesteryl ester from the HDL-A fraction and lost phospholipid to the HDL-A fraction. The HDL-A fraction maintained a low unesterified cholesterol/phospholipid molar ratio (0.23), while the apo-E-containing lipoproteins possessed a high ratio (0.75) characteristic of the perfusate HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE Family Study.

The familial aggregation of lipids and lipoproteins and plasma postheparin triglyceride lipases was investigated in 86 Caucasian families participating in the HERITAGE Family study, a study investigating the role of genetic factors in the adaptation to exercise training and its relationships with cardiovascular disease risk factors. Accordingly, sedentary subjects were recruited, tested for a battery of measurements, exercise trained for 20 weeks, and were re-measured. The present report includes plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities measured in 437 sedentary individuals (171 parents and 266 adult offspring) before training. Significant familial resemblance was observed for all the age-adjusted phenotypes. The pattern of familial correlations reveals no spouse correlations but significant parent-offspring and sibling correlations for total cholesterol, HDL-cholesterol and LDL-cholesterol with heritability (h2) estimates of 62%, 83%, and 50%, respectively. For plasma triglyceride concentrations (h2 = 55%) and HL activity (h2 = 40%), significant spouse correlations were found in addition to parent-offspring and sibling correlations, suggesting that common familial environment in addition to genetic factors contribute to the familial resemblance. For plasma LPL activity, there was no spouse correlation, but sex differences were found in the familial correlations with higher heritabilities in female pairs (h2 = 76%) compared to male pairs (h2 = 30%) and opposite-sex pairs (h2 = 44%). These results confirm the findings of previous family studies showing that genetic factors are major determinants of the familial resemblance in plasma lipids and lipoproteins and suggest the presence of sex differences in the heritability of postheparin LPL activity.

Adolescent↗
PubMedDate not supplied

Foam cells in explants of atherosclerotic rabbit aortas have receptors for beta-very low density lipoproteins and modified low density lipoproteins.

Beta-migrating very low density lipoproteins (beta--VLDL) and chemically modified low density lipoproteins (LDL), labeled with the fluorescent probe 3,3'-dioctadecylindocarbocyanine (Dil), were used to determine whether foam cells from atherosclerotic lesions have lipoprotein receptors similar to those of macrophages. The advantage of the Dil probe is that it produces a brilliant fluorescence due to its retention by the cells. When cells grown from intimal-medial explants of atherosclerotic rabbit aortas were incubated with Dil-labeled beta-VLDL, both smooth muscle cells and foam cells became fluorescent. However, when large amounts of unlabeled LDL were added to compete with the beta-VLDL for binding to the LDL receptors, Dil-labeled beta-VLDL binding to smooth muscle cells was blocked, and only the foam cells became highly fluorescent, due to the presence of specific receptors for beta-VLDL on those cells. The foam cells in the explants also became fluorescent when incubated with Dil-labeled acetoacetylated (AcAc) LDL. The same fluorescently labeled foam cells avidly bound IgG-coated erythrocytes. It was possible to inhibit the binding of the Dil-labeled AcAc LDL to aortic foam cells by the addition of fucoidin, a known inhibitor of modified LDL binding to macrophages. Foam cells that became fluorescent were similar to cells grown from the explants that contained an abundance of Oil red O positive lipid droplets and demonstrated high acid lipase activity. These results suggest that macrophages were the precursors of the foam cells derived from explants of atherosclerotic rabbit aortas. One difference we noted between these foam cells and macrophages, however, was that foam cells from the explants retained their cholesteryl esters under the same culture conditions that resulted in the loss of lipid from macrophages loaded with lipoproteins in vitro. The existence of receptors for beta-VLDL on aortic foam cells supports the contention that dietary cholesterol-induced beta-VLDL may be atherogenic lipoproteins in vivo.

Animals↗
PubMed1986

Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography.

In a study of 307 white patients who underwent coronary angiography, the relationship of coronary artery disease (CAD) to plasma levels of lipoprotein Lp(a) and other lipid-lipoprotein variables was examined. Lp(a) resembles low-density lipoprotein (LDL) in several ways, but can be distinguished and quantified by electroimmunoassay. CAD was rated as present or absent and was also represented by a quantitative lesion score derived from estimates of stenosis in four major coronary vessels. Coronary lesion scores significantly correlated with Lp(a), total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol levels by univariate statistical analysis. By multivariate analysis levels of Lp(a) were associated significantly and independently with the presence of CAD (p less than .02), and tended to correlate with lesion scores (p = .06). Among subgroups Lp(a) level was associated with CAD in women of all ages and in men 55 years old or younger. An apparent threshold for coronary risk occurred at Lp(a) lipoprotein mass concentrations of 30 to 40 mg/dl, corresponding to Lp(a) cholesterol concentrations of approximately 10 to 13 mg/dl. Plasma Lp(a) in white patients appears to be a major coronary risk factor with an importance approaching that of the level of LDL or HDL cholesterol.

Cholesterol↗
PubMed1989

Lipolytic surface remnants of triglyceride-rich lipoproteins are cytotoxic to macrophages but not in the presence of high density lipoprotein. A possible mechanism of atherogenesis?

Hypertriglyceridemic (HTG) serum, lipolyzed in vitro by purified bovine milk lipoprotein lipase, was found to be cytotoxic to cultured macrophages. Surviving macrophages contained numerous lipid inclusions similar to those found in foam cells. Individual lipoprotein fractions isolated from the lipolyzed HTG serum, including HDL, were also cytotoxic. Lipolysis of isolated lipoprotein fractions (either HTG or normal) allowed localization of cytotoxicity to postlipolysis remnant VLDL and chylomicron particles. The presence of a critical concentration of HDL in either the lipolysis mixture or the culture dishes inhibited the cytotoxicity. Below this critical concentration HDL itself became cytotoxic, producing lipid inclusions in surviving macrophages. The lipid fraction of the cytotoxic remnants contained the cytotoxic factor(s); neither FFA nor lysolecithin alone could account for this cytotoxicity. Postprandial lipemic sera from subjects with a brisk chylomicron response, when lipolyzed in vitro, were cytotoxic to cultured macrophages; neither fasted sera from these subjects, nor postprandial sera from normolipidemic subjects with a normal chylomicron response, were cytotoxic. Postheparin (in vivo lipolyzed) serum and its isolated lipoprotein fractions obtained 30 min after heparin injection in subjects with HTG were shown to be cytotoxic to macrophages; by 60 min most of the cytotoxicity had disappeared. The postprandial and postheparin observations support an in vivo significance for remnant-associated cytotoxicity. We hypothesize that cytotoxic remnants of lipolyzed VLDL and chylomicrons may be one of the major atherogenic lipoproteins. Further, we suggest that inhibition of the cytotoxicity of these remnants may be one important way that HDL prevents atherosclerosis.

Animals↗
PubMed1992

Lipoprotein lipase-mediated uptake and degradation of low density lipoproteins by fibroblasts and macrophages.

Lipoprotein lipase (LPL), the rate limiting enzyme for hydrolysis of lipoprotein triglyceride, also mediates nonenzymatic interactions between lipoproteins and heparan sulfate proteoglycans. To determine whether cell surface LPL increases LDL binding to cells, bovine milk LPL was added to upregulated and nonupregulated human fibroblasts along with media containing LDL. LDL binding to cells was increased 2-10-fold, in a dose-dependent manner, by the addition of 0.5-10 micrograms/ml of LPL. The amount of LDL bound to the cells in the presence of LPL far exceeded the capacity for LDL binding via the LDL receptor. Treatment of fibroblasts with heparinase and heparitinase resulted in a 64% decrease in LPL-mediated LDL binding. Compared to studies performed without LPL, more LDL was internalized and degraded in the presence of LPL, but the time course was slower than that of classical lipoprotein receptor mediated pathways. In LDL receptor negative fibroblasts, LPL increased surface bound LDL > 140-fold, intracellular LDL > 40-fold, and LDL degradation > 6-fold. These effects were almost completely inhibited by heparin and anti-LPL monoclonal antibody. LPL also increased the binding and uptake by fibroblasts of apolipoprotein-free triglyceride emulsions; binding was increased > 8-fold and cellular uptake was increased > 40-fold with LPL. LPL increased LDL binding to THP-1 monocytes, and increased LDL uptake (4.5-fold) and LDL degradation (2.5-fold) by THP-1 macrophages. In the absence of added LPL, heparin and anti-LPL monoclonal antibodies decreased LDL degradation by > 40%, and triglyceride emulsion uptake by > 50%, suggesting that endogenously produced LPL mediated lipid particle uptake and degradation. We conclude that LPL increases lipid and lipoprotein uptake by cells via a pathway not involving the LDL receptor. This pathway may be important for lipid accumulation in LPL synthesizing cells.

Animals↗
PubMed2002

The HIV protease inhibitor ritonavir increases lipoprotein production and has no effect on lipoprotein clearance in mice.

This study examined the effect of human immunodeficiency virus (HIV) protease inhibitor therapy on lipoprotein production and catabolism in vivo. The HIV protease inhibitor ritonavir was given to C57BL/6 mice fed either a basal low-fat diet or a Western type high-fat diet. Fasted mice were injected with Triton WR1339 followed by hourly blood collection to monitor lipoprotein production. Results showed that ritonavir increased VLDL triglyceride production by 30% over a 4 h period when mice were fed the low-fat basal diet. The ritonavir effect was more pronounced under high-fat feeding conditions, with a 2-fold increase in VLDL triglyceride production rate. Ritonavir did not alter hepatic expression levels of diacylglycerol acyltransferase or microsomal triglyceride transfer protein, but increased hepatic apolipoprotein B (apoB) secretion rates under both low- and high-fat dietary conditions. In contrast to its effect on lipoprotein production, ritonavir did not alter triglyceride-rich lipoprotein clearance from circulation under either dietary condition. Taken together, these results indicate that the hyperlipidemic effect of HIV protease inhibitors is a direct result of increased hepatic lipoprotein production. The mechanism appears to be related to their role in preventing proteasome-mediated degradation of apoB and activated sterol regulatory element binding proteins in the liver.

Acyltransferases↗
PubMed1987

Relationships of plasma estradiol, testosterone, and sex hormone-binding globulin with lipoproteins, apolipoproteins, and high density lipoprotein subfractions in men.

Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.

Adult↗
PubMed2001

Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid esters in low-density lipoprotein particles.

Estrogens are known to be powerful antioxidants in lipid-aqueous systems, as demonstrated by their inhibition of low-density lipoprotein (LDL) oxidation in vitro. Studies reporting that endogenous human estrogens could be rendered fat-soluble by esterification with fatty acids in vivo, and the subsequent detection of such esters in blood and fat tissue suggested a possible mechanism explaining how estrogens might protect LDL. Because of their lipophilicity, esterified estrogens may become incorporated in the lipoprotein structure, providing antioxidant potential for the particles. We incubated labeled 17beta-estradiol with ovarian follicular fluid and with plasma in the absence and presence of the LCAT inhibitor DTNB. This was followed by ultracentrifugal isolation of LDL and high-density lipoprotein and analysis of the radioactive label in the "ester" and "free" fractions purified from these lipoproteins. The results indicated that LCAT-mediated synthesis of esterified 17beta-estradiol occurred in high-density lipoprotein particles, and suggested a novel cholesterol ester transfer protein-mediated mechanism for their transfer to LDL particles.

Carrier Proteins↗
PubMed1990

Effects of omega-3 fish oils on plasma lipids, lipoprotein composition, and postheparin lipoprotein lipase in women with IDDM.

Because the apparent reduction in cardiovascular risk noted in nondiabetic populations that ingest diets rich in marine lipids containing omega-3 fatty acids is believed to result in part from their capacity to modify the composition and physicochemical behavior of lipoproteins, we sought to determine whether dietary supplementation with marine lipids might favorably affect lipoprotein composition in insulin-dependent diabetes mellitus (IDDM). Eight normolipidemic IDDM women (mean +/- SD age 29.8 +/- 4.7 yr) were studied before and 3 mo after receiving a marine-lipid concentrate (Super-EPA) containing 6 g omega-3 fatty acids and a total of 12 mg of cholesterol daily. Weight, insulin requirements, and glycosylated hemoglobin remained stable. After treatment, mean +/- SD plasma triglyceride (TG) levels fell (before, 81.7 +/- 22 mg/dl; after, 69.19 +/- 17; P less than 0.025). High-density lipoprotein2 (HDL2) cholesterol (before, 10.98 +/- 5.45 mg/dl; after, 18.43 +/- 7.93; P less than 0.01), its major apolipoprotein A-I (apoAI), and the major phospholipids (sphingomyelin and lecithin) all rose significantly. ApoB and plasma and low-density lipoprotein cholesterol levels and HDL3 composition were unchanged. Postheparin hepatic and lipoprotein lipase activities were unaffected by marine lipids. These data indicate that women with IDDM experience apparently beneficial effects on TG and HDL2 from dietary supplementation with omega-3 fatty acids administered in a low-cholesterol-containing oil without adversely affecting overall diabetes management. If these changes in lipoprotein concentration and composition prove to have antiatherogenic consequences and are free of long-term toxicity, these agents may have a role in the therapy of IDDM patients.

Adult↗
PubMed1999

Endogenously produced lipoprotein lipase enhances the binding and cell association of native, mildly oxidized and moderately oxidized low-density lipoprotein in mouse peritoneal macrophages.

It has been well established that purified lipoprotein lipase (LPL) can facilitate the cellular uptake of various native and modified lipoproteins when added exogenously to macrophages. Because activated macrophages express LPL endogenously, it was the aim of this study to investigate the effect of macrophage-produced LPL on the uptake of native low-density lipoprotein (LDL) and LDL that has been modified to various degrees by Cu(2+)-mediated oxidation. Cell binding and uptake of Eu(3+)-labelled native and oxidized LDL was determined in mouse peritoneal macrophages (MPM) from normal mice and induced mutant mice that lack LPL expression in MPM. We found that LPL expressed by MPM was able to increase cell binding and association of native LDL (by 121% and 101% respectively), mildly oxidized LDL (by 47% and 43%) and moderately oxidized LDL (by 30% and 22%). With increased levels of lipoprotein oxidation, the relative proportion of LPL-mediated LDL uptake decreased. This decrease was not due to weakened binding of LPL to oxidized LDL. The drastically increased uptake of highly oxidized LDL in MPM by scavenger-receptor-mediated pathways might dominate the simultaneous exogenous or endogenous LPL-mediated uptake of this lipoprotein. Competition experiments with positively charged poly(amino acids) furthermore suggested that histidine, arginine and lysine residues in LPL are important for the interaction between LDL and LPL. Our results imply that physiological levels of LPL produced by macrophages facilitate the uptake of native LDL as well as mildly and moderately oxidized LDL. This process might, in the micro-environment of arteries, contribute to the accumulation of macrophage lipids and the formation of foam cells.

Amino Acids↗
PubMed1999

The betaA4 amyloid peptide complexes to and enhances the uptake of beta-very low density lipoproteins by the low density lipoprotein receptor-related protein and heparan sulfate proteoglycans pathway.

We recently suggested that soluble beta-amyloid (betaA4) is a ligand of the low density lipoprotein receptor-related protein and heparan sulfate proteoglycan pathway. In the blood and in the cerebrospinal fluid, betaA4 is bound to apolipoprotein E containing lipoproteins. We examined how binding of betaA4 to beta-very low density lipoproteins (betaVLDL) alters their cellular metabolism. Compared with betaVLDL alone, complexes of betaVLDL and betaA4 were internalized, but not degraded at increased rates in fibroblasts and in rat hippocampal cells. The uptake of complexes of betaVLDL and betaA4 was not mediated by the low density lipoprotein receptor. BetaA4 not complexed to betaVLDL competed with the endocytosis of alpha2-macroglobulin and apolipoprotein E-enriched betaVLDL. The uptake of complexes of betaVLDL and betaA4 was inhibited by heparin, suramin, lactoferrin, the 39-kd receptor-associated protein, and alpha2-macroglobulin. Complexes of betaVLDL and betaA4 were taken up at reduced rates in Chinese hamster ovary cells partially (pgsB-650) or completely lacking (pgsA-745) proteoglycans. BetaA4 in which the positively charged amino acids between positions 13 and 17 (HHQKL) were replaced by glycine (GGQGL) failed to enhance the uptake of betaVLDL. Together, the data suggest that binding of betaA4 to betaVLDL produces particles that are endocytosed by low density lipoprotein receptor-related protein and HSPG. Complexes of betaVLDL and betaA4 had an intracellular half-life 4-fold that of native betaVLDL, did not undergo lysosomal degradation, and were resecreted into the culture medium. These findings represent the first identification of an endocytotic pathway for betaA4 and may be of relevance to the pathobiochemistry of neurodegenerative disorders.

Amyloid beta-Peptides↗
PubMed1976

Very low density lipoprotein. Dissociation of apolipoprotein C during lipoprotein lipase induced lipolysis.

The fate of apo C in rat plasma very low density lipoprotein (VLDL) during lipolysis was studied using VLDL labeled specifically with 125I-labeled apo C and purified bovine milk lipoprotein lipase. Incubations were carried out in vitro and included serum-containing systems and albumin containing systems. Free fatty acids generation proceeded with time of incubation in the two systems. It, however, was enhanced 1.5--2 fold by the presence of serum. 125I-labeled apo C equilibrated between very low and high density lipoprotein (HDL) in both systems even when enzyme was not present in the incubation medium, or when the incubation was carried out at 0 degrees C. Upon initiation of lipolysis, more 125I-labeled apo C was transferred to HDL and the transfer was proportional to the magnitude of free fatty acids release. 125I-labeled apo C was also progressively removed from VLDL in the albumin-containing system, although no known lipoprotein acceptor to apo C was present in the medium. The 125I-labeled apo C was recovered predominantly with the medium fraction of d greater than 1.21 g/ml (60--70%), and to a lesser degree with that of d= 1.019--1.21 g/ml. However, the relationship between lipolysis (measured as free fatty acids release) and removal of 125I-labeled apo C from VLDL were indistinguinshable in the albumin containing system and the serum containing system. On the basis of these observations, it is postulated that the removal of apo C during lipolysis of VLDL reflects the nature of the partially degraded VLDL particles, and is independent of the presence of a lipoprotein acceptor to apo C.

Albumins↗