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L Dory

Publications and source records attributed to L Dory.

At least 19 recordsLinked to original sources
PubMed2001

Caveolin-1 and caveolin-2 expression in mouse macrophages. High density lipoprotein 3-stimulated secretion and a lack of significant subcellular co-localization.

Evidence for caveolin expression in macrophages is scarce and conflicting. We therefore examined caveolin-1 and caveolin-2 expression in resident and thioglycollate-elicited mouse peritoneal macrophages (tg-MPM) and in the J774 mouse macrophage cell line by RT-PCR, ribonuclease protection assay, immunoblotting, and immunofluorescence. We found that relative to 3T3 cells, resident MPM and tg-MPM express low amounts of caveolin-1 (45 and 15% of those in 3T3 fibroblasts, respectively), while J774.A1 cells do not express any. Caveolin-2, on the other hand, is expressed in all cells examined, with highest expression in tg-MPM and the lowest in J774 cells. The relative levels of caveolin expression in the various cells correspond well with their respective mRNA levels, as measured by ribonuclease protection assay. Caveolin-1, present primarily on the cell surface, does not co-localize significantly with caveolin-2, which is present primarily in the Golgi compartment in all macrophages studied. Loading of tg-MPM with cholesterol or variations in unesterified cholesterol content appear to have little effect on the level of caveolin-1 or -2 expression or their distribution. Stimulation of cholesterol efflux by HDL(3) leads to caveolin-1 and caveolin-2 secretion to the cell culture medium, a process not detected in the absence of HDL(3). The lack of significant co-localization of the two caveolin isoforms in primary macrophages and their secretion in the presence of HDL(3) provides an interesting and physiologically relevant model system to study additional aspects of caveolin function.

Animals↗
PubMed2001

High cholesterol diet down regulates the activity of activator protein-1 but not nuclear factor-kappa B in rabbit brain.

Cardiovascular risk factors and alterations in cholesterol metabolism are implicated in the pathogenesis of Alzheimer's dementia (AD). The hypercholesterolemic rabbit model of atheroslerosis and AD was utilized in this study to examine oxidative stress related changes in the brain. The high cholesterol diet induced dramatic increases in plasma and liver cholesterol concentrations, but brain cholesterol levels remained constant. Similar effects have been found regarding lipid oxidation products. The amounts of conjugated dienes, trienes and thiobarbituric acid reactive substances (TBARS) significantly increased in the plasma of cholesterol treated animals while the brain cortex showed no signs of increased lipid peroxidation. The oxidative damage sensitive nuclear transcription factor kappa B (NF-kappaB) and activator protein-1 (AP-1) diverged in their responses. Accordingly, the AP-1 DNA binding activity decreased by more than 50% in brain nuclear protein extracts while the NF-kappaB binding activity remained unaltered by the hypercholesterol diet. These results indicate that despite the relative resistance of the central nervous system to dietary manipulation of its lipid composition and lipid peroxidation products, chronic dietary intake of cholesterol can alter the function of certain proteins involved in regulation of gene expression in the brain.

Animals↗
PubMed2000

Dietary fat modulates serum paraoxonase 1 activity in rats.

We examined the effects of dietary fats with specific fatty acid compositions, on serum paraoxonase (PON1) activity in rats. Male adult Sprague-Dawley rats were divided randomly into four dietary groups. One group received the control diet [AIN 93M with soybean oil (5 g/100 g diet)], whereas the remaining three groups received the modified control diet supplemented with (15 g/100 g diet) triolein, tripalmitin or fish oil, respectively. After 20 d, blood was obtained after overnight food deprivation and PON1 activity was determined. Serum lipids and lipid components of lipoproteins were also determined. Serum PON1 activity [micromol/(L.min)] was significantly (P: < 0.05) higher in triolein (98 +/- 6) and lower in fish oil (41 +/- 4), compared with tripalmitin-fed rats (63 +/- 11). Serum PON1 activity in tripalmitin-fed rats was comparable to that of controls (67 +/- 9). Serum PON1 activity correlated significantly with serum lecithin:cholesterol acyltransferase (LCAT) activity (r = 0.77, P: < 0.001) and was transported in blood principally in association with the denser subfraction of HDL, very high density lipoprotein (VHDL; d > 1.15 kg/L). Serum PON1 activity correlated strongly with serum lipids as well as lipids of VLDL, HDL and its subfractions. Multiple linear regression analysis, however, showed a significant relationship of serum PON1 activity, principally with the phospholipids of VHDL (r = 0.47, P: < 0.002). These data suggest that the modulation of serum PON1 activity by dietary fat may be mediated via the effect of the specific fatty acids on the synthesis and secretion of VHDL, the subfraction of HDL that transports the majority of PON1 in the blood.

Animals↗
PubMed2000

Hyperbaric oxygen reduces the progression and accelerates the regression of atherosclerosis in rabbits.

We studied the effect of hyperbaric oxygen (HBO) treatment on the extent of diet-induced accumulation of lipid oxidation products in rabbit plasma and tissues, on plasma paraoxonase activity, and on the extent of progression and regression of atherosclerotic lesions in the rabbit aorta. HBO treatment of cholesterol-fed rabbits dramatically reduces the development of arterial lesions despite having little or no effect on plasma or individual lipoprotein cholesterol concentrations. Compared with no treatment in cholesterol-fed animals, HBO treatment also substantially reduces the accumulation of lipid oxidation products (conjugated dienes, trienes, and thiobarbituric acid-reactive substances) in plasma, in the low density lipoprotein and high density lipoprotein fractions of plasma, in the liver, and in the aortic tissues. In addition, HBO treatment prevents the decrease in plasma paraoxonase activity observed in rabbits fed cholesterol-rich diets. Similarly, in regression studies, HBO treatment has no effect on the rate of plasma (or lipoprotein) cholesterol decline but significantly accelerates aortic lesion regression compared with no treatment. Direct measures of aortic cholesterol content support these morphological observations. On the basis of these results, we conclude that repeated, but relatively short, exposure to HBO induces an antioxidant defense mechanism(s) that is responsible for retarding the development or accelerating the regression of atherosclerotic lesions.

Animals↗
PubMed1999

Fatty acids alter time dependent loss of apolipoprotein E expression by primary cultures of rat hepatocytes.

Although the phenomenon of intracellular apolipoprotein E (apoE) degradation has been reported in other cell types, the fate of newly synthesized apoE in the liver is not well understood. In the present study, we examined the expression (the balance of synthesis, secretion, and degradation) of apoE in primary cultures of rat hepatocytes and compared it with albumin, a typical secretory protein. Synthesis and secretion of [(35)S]apoE was diminished in primary hepatocytes cultured for more than 2 days, in agreement with an observed decrease in apoE mRNA. Cells cultured for 1 day and labeled for up to 4 hours secreted total protein, apoE, and albumin, linearly. The apparent rates of synthesis for apoE and albumin were similar (1,158 vs. 1,334 dpm/mg/min) but rates of their secretion differed significantly (225 vs. 1,159 dpm/mg/min). Pulse-chase experiments indicated that cell-associated [(35)S]albumin was secreted without degradation, whereas significant quantities of newly synthesized apoE were degraded. The overall synthesis and secretion of total proteins, including secretion of apoE, was enhanced by oleic acid (1 mmol/L). However, this effect may not be limited to oleic acid because other fatty acids showed a similar effect on apoE mRNA abundance. In control cells, apoE was found to associate with high density lipoproteins predominantly, although the fraction associated with very low density lipoprotein was increased in hepatocytes incubated with oleic acid. Overall, the findings from this study suggest that the level of apoE expression by primary hepatocytes is dependent on the age of the culture. The study also indicates that the phenomenon of apoE degradation occurs in primary hepatocytes.

Journal Article↗
PubMed1998

Fatty acids modulate lecithin:cholesterol acyltransferase secretion independently of effects on triglyceride secretion in primary rat hepatocytes.

The regulation of plasma lecithin:cholesterol acyltransferase (LCAT) expression is not well understood. Although oleic acid increases both the secretion of triglycerides and LCAT by primary rat hepatocytes, the effect of other fatty acids (FA) on LCAT secretion is not known. This study was designed to examine the effect of FA on the hepatic secretion of LCAT, triglyceride and apolipoprotein A-1 (apoA-1). Primary rat hepatocytes were incubated with serum-free medium, supplemented with individual FA (0-1 mmol/L) for 22-24 h. Preliminary studies indicated a linear secretion of LCAT up to 24 h in both control and FA-treated cells. When hepatocytes were incubated with 1 mmol/L FA, the LCAT secretion increased 50-100% (P < 0.01) in the presence of the 18-carbon FA (stearic, oleic, elaidic and linoleic acids), whereas the presence of butyric, lauric and palmitic acids had no significant effect. LCAT secretion decreased (P < 0.01) in the presence of docosahexaenoic acid (DHA). All FA (except DHA) significantly enhanced triglyceride secretion; however, only the 18 carbon FA significantly stimulated the synthesis and secretion of apoA-1 and secretion of LCAT. The secretion of LCAT correlated with apoA-1 secretion (r = 0.88, P = 0.004) but not with triglyceride secretion (r = 0.55, P = 0.12). Treatment with oleic acid resulted in a 1.5-fold increase in hepatocyte LCAT mRNA accumulation, whereas butyrate and palmitate had no effect. These data indicate that FA that promote the apparent synthesis and secretion of apoA-1 also stimulate the secretion of LCAT in vitro, suggesting a coordinate regulatory mechanism for apoA-1 and LCAT expression.

Animals↗
PubMed1997

Investigation of plasma membrane-associated apolipoprotein E in primary macrophages.

Our previous studies identified the lysosome as the compartment for degradation of newly synthesized apoE in primary macrophages. Lysosomal degradation of newly synthesized apoE is extensive and rapid (> 50% in 60 min). In the present study we tested the hypothesis that the macrophage cell surface is part of the itinerary of apoE in its path to the lysosomes. We therefore examined the existence and size of the apoE pool associated with the macrophage cell surface. Such a pool may not only provide a mechanism of targeting apoE for lysosomal degradation, by endocytosis, but also have important implications for the metabolism of lipoproteins by macrophages. Treatment of macrophages with heparin (10 micrograms/ml and 5 mg/ml) and heparinase I (1 U/ml), which releases substantial amounts of apoE from HepG2 cells, results in no additional release of apoE from macrophages. Treatment of macrophages with xyloside (1 mM) or GRGDTP (500 micrograms/ml) does not decrease the extent of cell-associated apoE. Both immunogold labeling, followed by electron microscopy, and immunofluorescent labeling and light microscopy further confirm the lack of significant amounts of cell surface-associated apoE in macrophages. In contrast, immunolabeled apoE is readily observed in permeabilized cells. Taken together, these data indicate the absence of significant apoE-glycosaminoglycan interaction at the macrophage cell surface. The lack of such an interaction is likely due to paucity of heparan sulfate proteoglycans on the macrophage cell surface, when compared to hepatocytes. Along with our previous observations. (Deng. J., V. Rudick, and L. Dory, 1995. J. Lipid Res. 36:2129-2140), these results suggest direct targeting of a portion of newly synthesized apoE from trans-Golgi network to lysosomes for degradation, without involving the plasma membrane and endocytosis.

Animals↗
PubMed1995

Lysosomal degradation and sorting of apolipoprotein E in macrophages.

We previously reported that a substantial amount of newly synthesized apoE in mouse macrophages is degraded prior to secretion; a portion of this pool of apoE can be rescued by the addition of HDL3 to the incubation medium. In the present studies, the location and nature of the intracellular degradation of apoE were more closely examined. Inhibitors of protein trafficking (brefeldin A) as well as a number of protease inhibitors were used. The experiments using brefeldin A (5 micrograms/ml) clearly established that neither the endoplasmic reticulum nor the Golgi complex are the sites of apoE degradation. Using a pulse-chase design, [35S]apoE cannot be chased out in the presence of brefeldin A and remains undegraded within the cell. The accumulated apoE lacks the sialic acid residues, indicating that this final stage of processing must occur in the trans-Golgi network or later. Lysosomotropic agents, ammonium chloride and chloroquine, on the other hand, inhibit apoE degradation by over 70 and 80%, respectively, while total cell protein degradation remains unaffected. Similarly, a cocktail consisting of four lysosomal protease inhibitors (pepstatin, E-64, chymostatin, and antipain), inhibits specifically apoE degradation by over 60%. In contrast, ALLN, an inhibitor of Ca(2+)-dependent cysteine proteases, has a moderate effect on apoE degradation (30% inhibition) and a more pronounced effect on total protein degradation. These data suggest that the site of intracellular apoE degradation in the macrophage is the lysosome. These conclusions are supported by light and electron microscopy of macrophages, clearly showing the presence of immunoreactive apoE (along with cathepsin D) in the endosomal/lysosomal compartment of control and lysosomotropic agent-treated cells. In contrast, little or no labeling is seen in this compartment in brefeldin A-treated cells. At lower concentrations of the lysosomotropic agents, the extent of inhibition of apoE degradation is compensated for by its increased secretion, in a manner analogous to the effect of these agents on lysosomal enzymes. Higher concentrations of these agents, which lead to a profound inhibition of apoE degradation, also specifically block apoE secretion. The block in apoE secretion in the presence of high concentrations of chloroquine leads to undiminished or higher concentrations of immunoreactive apoE in the endosomal/lysosomal compartment, suggesting that apoE is targeted for lysosomal degradation directly, without prior secretion or surface association. These data strongly suggest pH-dependent sorting of apoE in macrophages to the degradative and secretory pathways and imply a protein-protein interaction in the process.

Animals↗
PubMed1993

Exogenous phospholipase C specifically inhibits apoE expression in mouse peritoneal macrophages.

Treatment of cholesterol-loaded mouse peritoneal macrophages with exogenous phospholipase C results in a specific and dose-dependent inhibition of apoE secretion. The inhibition of apoE secretion is secondary to the rapid and specific inhibition of its synthesis. The profound changes in rates of apoE synthesis are not accompanied by changes in the levels of apoE mRNA, an observation strongly suggestive of translational regulation of expression. The changes in apoE expression coincide with, or are preceded by a three-fold increase in membrane-bound protein kinase C activity, pointing out the potential importance of this signal transduction pathway in regulating apoE expression at a posttranscriptional locus.

Animals↗
PubMed1993

Post-transcriptional regulation of apolipoprotein E expression in mouse macrophages by phorbol ester.

Phorbol ester-mediated differentiation of THP-1 cells (a human monocytic cell line) into mature macrophages is associated with a transcriptional induction of apolipoprotein E (apoE) expression [Auwerx, Deeb, Brunzell, Peng and Chait (1988) Biochemistry 27, 2651-2655]. Endotoxin, on the other hand, which may also act through activation of protein kinase C, is a potent inhibitor of apoE expression in mouse macrophages [Werb and Chin (1983) J. Biol. Chem. 258, 10642-10648]. The present experiments examine the effect of phorbol ester, an activator of protein kinase C, on the apoE expression in mouse thioglycollate-elicited peritoneal macrophages. Phorbol ester inhibits apoE expression in a specific, time- and dose-dependent manner. A 75% inhibition in the rate of apoE secretion, but not that of total protein, was observed following a 4.5 h incubation with 160 nM phorbol ester, although nearly full inhibition was obtained with 40 nM. The changes in apoE secretion were paralleled by similar changes in apoE synthesis, indicating synthesis as the primary site of action. The decreased rates of apoE synthesis are shown not to be due to increased apoE degradation. The profound inhibition of apoE synthesis was not accompanied by significant changes in apoE mRNA levels at any concentration of phorbol ester (up to 16 microM), or length of treatment (up to 24 h), suggesting a post-transcriptional locus of regulation of apoE expression. Although the early changes in apoE synthesis correlate with increased microsomal protein kinase C activity, the suppression of apoE expression persists even during conditions of nearly complete (> 95%) loss of protein kinase C activity, suggesting that the direct or indirect effect of protein kinase C on apoE expression is mediated by a stable phosphorylated protein, or that the observed effects are mediated through a protein kinase C species that is not readily downregulated by phorbol esters. The presented studies clearly demonstrate the potential importance of the translational regulation of apoE expression through the protein kinase C signal transduction pathway.

Animals↗
PubMed1991

Regulation of apolipoprotein E secretion by high density lipoprotein 3 in mouse macrophages.

Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experiments demonstrate that the effect of HDL3, and to a lesser extent HDL2, on apoE secretion is specific, concentration-dependent, and may require interaction with the HDL receptor. Very low density lipoproteins (VLDL) and low-density lipoproteins (LDL) fail to specifically stimulate apoE secretion by cholesterol-loaded macrophages. The effect of HLD3 is maximal at 25-50 micrograms/ml (0.26-0.52 microM) and can be totally abolished by mild nitrosylation (with 3 mM tetranitromethane (TNM)). Data are also presented to indicate that the increased rate of apoE secretion in the presence of HDL3 is not due to a "protective" effect of this lipoprotein on possible proteolytic degradation or cellular reuptake of apoE secreted into the media. The stimulatory effect of HDL on apoE secretion can be clearly dissociated from cholesterol efflux; HDL stimulates apoE secretion from oxysterol-treated cells in the absence of measurable cholesterol efflux, while TNM-HDL promotes substantial cholesterol efflux from cholesterol-loaded cells but has no effect on apoE secretion. The kinetics of apoE synthesis and secretion, determined in short-term labeling studies, demonstrate that under all experimental conditions examined a substantial portion of cellular apoE is not secreted. Furthermore, in cholesterol-loaded cells HDL3 increases apoE secretion essentially by diversion of a greater portion of cellular apoE pool for secretion. While HDL3 has no effect on the rate of apoE synthesis, cellular apoE turns over two-fold faster in cells incubated in the presence of HDL3 than in its absence (t 1/2 = 11 +/- 2 and 22 +/- 4 min, respectively), an observation corresponding well with the changes in the rates of apoE secretion under similar conditions. The HDL3-mediated increase in apoE secretion by cholesterol-loaded macrophages suggests another mechanism by which HDL exerts a protective effect in the development of atherosclerosis; increased contribution to the metabolic pool of apoE by peripheral tissues may lead to a more effective clearance of peripheral cholesterol by the liver (reverse cholesterol transport).

Animals↗
PubMed1990

Hepatic low density lipoprotein receptors, HMG-CoA reductase, and plasma lipids and apolipoproteins in high- and low-responding rhesus monkeys: effect of cholestyramine treatment.

Plasma lipids and apolipoproteins, and hepatic LDL receptor and HMG-CoA reductase activities in biopsy samples were measured in high- and low-responding rhesus monkeys maintained on a cholesterol-rich and regular diets. The effect of a 30-day cholestyramine treatment on the above parameters under both dietary conditions was also determined. On the cholesterol-rich diet the high-responders, when compared to the low-responders, had several-fold increased plasma cholesterol and apoB concentrations and significantly lower HDL apoA-I and cholesterol concentrations. Hepatic LDL receptor and HMG-CoA reductase activities were not detectable in the high-responders, while the low-responders expressed a reduced number of LDL receptors of normal affinity. Administration of cholestyramine resulted in a rapid induction of the hepatic LDL receptors in the high-responders and a small additional increase in the low-responders. Cholestyramine treatment also stimulated the expression of the hepatic HMG-CoA reductase in both groups of monkeys. These changes were accompanied by a dramatic drop in plasma cholesterol and apoB concentrations in the high-responders and, to a lesser extent, in the low-responders. Plasma HDL concentrations in the high-responders rose to levels higher than those seen in the low-responders. The affinity and receptor number were similar in both groups of monkeys on the control diet, but the low-responders had significantly higher HMG-CoA reductase activities. Administration of cholestyramine during the control diet had a small but significant additional effect on the hepatic LDL receptors of the low-responders but not of the high-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux.

ApoE synthesis and secretion, as a function of cellular cholesterol content and cholesterol efflux, was studied in thioglycolate-elicited mouse peritoneal macrophages. As expected, loading elicited macrophages with cholesterol induced a 5-fold increase in apoE secretion and a 2.5-fold increase in cellular apoE content over a 5-h period. Treatment of cholesterol-loaded cells with HDL3 further increased apoE secretion 1.7-fold and decreased cellular cholesterol by 20%. Treatment of cholesterol-loaded cells with HDL3 and SAH 58.035 (an ACAT inhibitor) increased apoE secretion 2.4-fold and decreased cellular cholesterol content by 35%. Treatment of the cells with the ACAT inhibitor alone suppressed apoE secretion by 40% but did not change cellular cholesterol content. Northern blot analysis of RNA indicated that cholesterol loading increased apoE mRNA 2-fold. ApoE mRNA levels were not further affected by treatment with HDL3 and/or the ACAT inhibitor. Cholesterol-loaded cells, in the absence of HDL3, secreted apoE into the media in two fractions as determined by column chromatography: a large molecular weight complex, (larger than HDL), and an essentially lipid-free protein. In the presence of HDL3, the cells secreted apoE in three fractions: a large molecular weight complex, an essentially lipid-free protein, and over 50% of apoE associated with HDL. In the process, HDL3 became larger and eluted in a position identical to that of HDL2. A small amount of HDL3-derived material was also transformed to an LDL-size particle. Incubation of HDL3 in the absence of cholesterol-loaded cells did not produce these changes. It is concluded that cholesterol-loading increases apoE mRNA content and apoE synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗
PubMed1987

Interstitial fluid lipoproteins.

While a wide variety of techniques has been used to collect samples of interstitial fluid, most of our detailed knowledge about the composition of interstitial fluid lipoproteins has come from lymph collection studies. The considerable variability of lymph data probably reflects the effect of variable metabolic modification and different capillary permeabilities on the lipoprotein composition of interstitial fluid. All density classes of plasma lipoproteins are present in lymph. In peripheral lymph, the lymph/plasma concentration ratios of lipoproteins vary from 0.03 for VLDL-sized particles to 0.2 for HDL. Lymph from more permeable vascular beds, such as lung and myocardium, contains proportionately more lipoproteins. Their lymph/plasma concentration ratios vary from 0.1 to 0.6. In general, lymph lipoproteins are more heterogeneous in size than their plasma counterparts. Lymph HDL and LDL contain larger and smaller particles than their plasma equivalents. Lymph lipoproteins have unusual shapes (square packing and discoidal), chemical compositions, and molecular charge, which suggest de novo formation and/or extensive peripheral modification. Lymph HDL and LDL are enriched in free cholesterol. Lymph HDL also has increased cholesterol/protein and phospholipid/protein (especially sphingomyelin) ratios (Sloop, C.H., L. Dory, and P.S. Roheim, unpublished observations). Lymph HDL apoprotein composition differs from that of plasma, with an increase in apoE and apoA-IV content relative to apoA-I. These discoidal HDL particles may be products of an initial stage of reverse cholesterol transport. We believe further study of their metabolic fate would give important information concerning the later stages of reverse cholesterol transport.

Animals↗
PubMed1986

Peripheral synthesis and isoform distribution of dog apoprotein E. An in vivo approach.

Purified dog plasma apo-E is composed of four major isoforms with the following pI values: 5.40, 5.31, 5.26, and 5.22. Treatment with neuraminidase suggests that the multiple forms are due to progressive sialation. The acidic isoforms (pI = 5.22 and less), rarely detectable in plasma lipoprotein samples (except in the d less than 1.05 g/ml fraction of cholesterol-fed dogs), are present in high concentrations in the interstitial fluid high density lipoprotein fraction I (HDLI) of cholesterol-fed dogs, a lipoprotein recently described (Dory, L., Boquet, L.M., Hamilton, R.L., Sloop, C.H., and Roheim, P.S. (1985) J. Lipid Res. 26, 519-527). Apo-Es0 (the most basic isoform) is a major constituent of the plasma d less than 1.05 g/ml fraction, but it is usually only a minor component of other plasma or interstitial fluid lipoproteins. This is likely a reflection of the prolonged residence time of a specific lipoprotein species in this density range, resulting in more extensive desialation. Peripheral apo-E synthesis has been measured under in vivo conditions using a hindlimb cannulation of the lymphatics and collection of prenodal peripheral lymph. Following injection of [3H]leucine or [35S]methionine into the dorsal skin of the toes, the specific activity of the interstitial fluid apo-E far exceeded that of plasma apo-E at all time points examined. Incorporation was measurable 30 min after the isotope injection and peaked at 150 min in control dogs and between 120-150 min in cholesterol-fed dogs. The rate of peripheral synthesis of apo-E in cholesterol-fed dogs appeared to be twice that of control dogs. The newly synthesized and secreted apo-E preferentially associated with the disc-shaped HDLI of the interstitial fluid; less than 15% of the apo-E-associated radioactivity was recovered in the d less than 1.05 g/ml fraction, despite the fact that this fraction contains well over 50% of the total interstitial fluid apo-E mass. The newly secreted, HDLI-associated apo-E can be converted by neuraminidase into apo-Es0.

Animals↗