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R T Dean

Publications and source records attributed to R T Dean.

At least 37 records · Page 2Linked to original sources
PubMed1999

Human apo-lipoprotein B from normal plasma contains oxidised peptides.

Oxidation of low density lipoprotein (LDL) may be atherogenic, but radical-initiated oxidation of its apoprotein B-100 (apoB) has been little studied. Transition metal ions iron and copper are candidates for mediating radical oxidation of LDL in vivo. Therefore, we studied the copper-ion-induced oxidation of apoB in human LDL. Using HPLC methods developed in our recent work, we studied the destruction of native and the generation of six oxidised amino acids; we also assessed the release of peptides from the LDL particle by FPLC. We observed time-dependent losses of apoB histidine, lysine and glycine. Long-lived reactive species, the reductant DOPA, and the oxidant hydroperoxides of valine and leucine (measured as hydroxides after reduction), were generated. Their relative abundance (mol/mol of parent amino acid) was DOPA > o- and m-tyrosine > dityrosine, valine-hydroxides, leucine hydroxides. Low molecular weight fragments were also released from the LDL in a time-dependent manner, contained hydroperoxides sensitive to GSH peroxidase, and generated radicals on reaction with iron-EDTA. The fragments contained peptides active in the quinone redox cycling procedure, comprising 0.25% of the supplied LDL amino acids. Characteristic peptides were present in each FPLC fraction containing the fragments, as judged by further HPLC fractionation. Some fragments were present in the unoxidised LDL preparations, and when these were largely removed by FPLC, copper oxidation could still generate fragments, suggesting that those present in the starting material might indicate prior oxidation. Concordantly, we found that fresh plasma LDL apoB contained 43% of total plasma protein-bound oxidised amino acids, and with the same relative abundance. We conclude that plasma proteins including apoB are subject to physiological oxidation, similar to that inflicted by copper ions; the latter may contribute to intimal LDL oxidation, which could be the source of oxidised plasma apoB.

Amino Acids↗
PubMed1999

Are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?

To investigate the involvement of oxidative tissue damage in the pathogenesis of murine cerebral malaria (CM), brain levels of protein carbonyls, 3,4-dihydroxyphenylalanine (DOPA), o-tyrosine, and dityrosine were measured during Plasmodium berghei ANKA (PbA) and P. berghei K173 (PbK) infections. During PbA infection in a CM model, brain levels of the substances were similar to those in uninfected mice. The role of phagocyte-derived reactive oxygen species in the pathogenesis of CM was examined in gp91phox gene knockout mice. The course of CM in these mice was the same as in their wild type counterparts. To examine whether superoxide production in the central nervous system could have occurred via increased xanthine oxidase activity, brain concentrations of urate were measured in CM mice and in mice infected with PbK (which does not cause CM). Brain urate concentration increased significantly in both groups of mice, suggesting that purine breakdown is not specific to CM. These results indicate that reactive oxygen species probably do not contribute to the pathogenesis of murine CM.

Animals↗
PubMed1999

Prooxidant and antioxidant activities of macrophages in metal-mediated LDL oxidation: the importance of metal sequestration.

Murine macrophages incubated in metal-supplemented RPMI could block or promote oxidation of low-density lipoprotein (LDL) depending on the degree of metal supplementation. Only at high concentrations of Cu (1 micromol/L) and Fe (30 micromol/L) were cells prooxidant, leading to an accelerated rate of LDL oxidation over that measured in comparable cell-free media. At lower concentrations of Cu and Fe in RPMI, LDL oxidation in the presence of macrophages was inhibited relative to the cell-free condition. This appeared to be dependent on a stable modification of the culture medium, because preconditioning of media by incubation with macrophages could also decrease their capacity to sustain subsequent cell-free LDL oxidation. This was due, in part, to a removal of metal from the media during preconditioning. However, resupplementation of media with metals did not fully restore oxidative capacity, indicating that other cell-dependent antioxidant modifications occurred. This did not involve significant alterations to the thiol content of the media. This study highlights the complexity of the role that cells such as macrophages have with regards to LDL oxidation in vitro and demonstrate that there are both antioxidative and prooxidative components.

Adult↗
PubMed1999

Coexistence of oxidized lipids and alpha-tocopherol in all lipoprotein density fractions isolated from advanced human atherosclerotic plaques.

After investigation of the contents and redox status of antioxidants and lipids in homogenates of both normal artery and atherosclerotic plaque, we now investigated them in the density fractions (very low, low, high, and protein fractions) of atherosclerotic plaque freshly obtained from carotid endarterectomy. By using the optimum extraction method (homogenization in carbonate buffer) and after density gradient ultracentrifugation, we isolated and characterized density fractions of plaque for apolipoproteins, size and contents of alpha-tocopherol (alpha-TOH), unesterified cholesterol, cholesteryl linoleate (Ch18:2), and hydroxides and hydroperoxides of Ch18:2, ie, Ch18:2-O(O)H. The distribution of apolipoproteins was more heterogeneous than that in the corresponding lipoproteins isolated from blood, and the majority of material in all plaque density fractions was present in large particles eluting in the void volume of gel-filtration columns. The content of unesterified cholesterol per unit of protein in low- and high-density fractions was 10-fold that in corresponding plasma lipoproteins. Low- and very-low-density fractions contained most of the lesion lipids and alpha-TOH. Two to five percent of lesion Ch18:2 was present as Ch18:2-O(O)H and distributed more or less equally among all density fractions, yet the content of alpha-TOH per unit of Ch18:2 was higher than that in corresponding plasma lipoproteins. These results demonstrate that alpha-TOH and oxidized lipids coexist in all lesion density fractions, further supporting the notion that large proportions of lipids in lipoproteins of advanced stages of atherosclerosis are oxidized. However, although not ruling it out, our results do not support the suggestion that advanced stages of atherosclerosis are associated with gross deficiencies in the lipoproteins' vitamin E content.

Aged↗
PubMed1999

Oxysterol efflux from macrophage foam cells: the essential role of acceptor phospholipid.

Oxidized forms of cholesterol (oxysterols) are present in atherosclerotic lesions and may play an active role in lesion development. For example, 7-ketocholesterol (7KC) inhibits cholesterol efflux from macrophage foam cells induced by apolipoprotein A-I (apoA-I). Such oxysterols may promote foam cell formation in atherosclerotic lesions by preventing effective clearance of excess cholesterol. ApoA-I also induces phospholipid (PL) export from foam cells and it has been suggested that cholesterol efflux is dependent upon PL association with the apolipoprotein. In the current study, the effect of oxysterol enrichment of foam cells on phospholipid efflux was measured. Export of cellular PL to apoA-I from 7KC-enriched foam cells was inhibited to the same extent as cholesterol, indicating that the reduced cholesterol export may be a consequence of a decline in the capacity of the foam cells to generate PL/apoA-I particles capable of accepting cellular cholesterol. Incubation of foam cells with pre-formed PL/apoA-I discs increased cholesterol export from 7KC-enriched cells to levels seen in 7KC-free cells. Foam cells produced by uptake of oxidized LDL, which contain similar amounts of 7KC plus other oxidation products, expressed a more profound inhibition of PL export to apoA-I. Cholesterol efflux from these cells improved only partially by provision of PL-containing acceptors. Efflux of 7KC from both foam cell types occurred to PL/apoA-I discs but was only minimal to lipid-free apoA-I, indicating that export of this oxysterol is more dependent than cholesterol upon the presence of extracellular phospholipid.

Animals↗
PubMed1998

Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque.

Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine) or oxidation has been obtained by immunochemical methods; the specificities of these antibodies are unclear. Here we present chemical determinations of six protein-bound oxidation products: dopa, o-tyrosine, m-tyrosine, dityrosine, hydroxyleucine and hydroxyvaline, some of which reflect particularly oxy-radical-mediated reaction pathways, which seem to involve mainly the participation of transition- metal ions. We compared the relative abundance of these oxidation products in normal intima, and in human carotid plaque samples with that observed after radiolytically generated hydroxyl radical attack on BSA in vitro. The close similarities in relative abundances in the latter two circumstances indicate that hydroxyl radical damage might occur in plaque. The relatively higher level of dityrosine in plaque than that observed after radiolysis suggests the additional involvement of HOCl-mediated reactions in advanced plaque.

Adult↗
PubMed1998

Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam cells: a potential anti-atherogenic function?

Apolipoprotein J (apo J) is a secreted glycoprotein of which the exact function remains a matter for speculation. Apo J has been implicated in such diverse processes as sperm maturation, regulation of complement activation, programmed cell death, tissue remodelling and lipid transport. In this study a possible role for apo J in lipid transport was explored. Mouse peritoneal macrophages were incubated with acetylated low-density lipoprotein (AcLDL) to produce foam cells containing cholesterol and cholesteryl esters. Incubation of the foam cells with physiological concentrations of purified apo J led to a dose-dependent export of cholesterol. The appearance of cholesterol in the medium was associated predominantly with a decline in intracellular cholesteryl esters rather than intracellular free cholesterol. The kinetics of cholesterol release to apo J were similar to apo A-I, an established promoter of cholesterol efflux. Apo J was also shown to induce phospholipid efflux from cells, whereas the cholesterol exported to the medium was associated with the apo J. Studies using foam cells from apo E-null mice showed that the cholesterol exported to the medium was independent of apo E production by the cells. These results present the first evidence that apo J can promote cholesterol efflux from foam cells and indicates that it might have a function in cellular cholesterol homoeostasis in both normal and pathological situations.

Animals↗
PubMed1998

The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage.

A major product of hydroxy-radical addition to tyrosine is 3, 4-dihydroxyphenylalanine (DOPA) which has reducing properties. Protein-bound DOPA (PB-DOPA) has been shown to be a major component of the stable reducing species formed during protein oxidation under several conditions. The aim of the present work was to investigate whether DOPA, and especially PB-DOPA, can mediate oxidative damage to DNA. We chose to generate PB-DOPA using mushroom tyrosinase, which catalyses the hydroxylation of tyrosine residues in protein. This permitted us to study the reactions of PB-DOPA in the virtual absence of other protein-bound oxidation products. The formation of two oxidation products of DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG) and 5-hydroxy-2'-deoxycytidine (5OHdC), were studied with a novel HPLC using gradient elution and an electrochemical detection method, which allowed the detection of both DNA modifications in a single experiment. We found that exposure of calf thymus DNA to DOPA or PB-DOPA resulted in the formation of 8oxodG and 5OHdC, with the former predominating. The formation of these DNA oxidation products by either DOPA or PB-DOPA depended on the presence of oxygen, and also on the presence and on the concentration of transition metal ions, with copper being more effective than iron. The yields of 8oxodG and 5OHdC increased with DOPA concentration in proteins. Thus PB-DOPA was able to promote further radical-generating events, which then transferred damage to other biomolecules such as DNA.

Basidiomycota↗
PubMed1998

Presence of dopa and amino acid hydroperoxides in proteins modified with advanced glycation end products (AGEs): amino acid oxidation products as a possible source of oxidative stress induced by AGE proteins.

Glycation and subsequent Maillard or browning reactions of glycated proteins, leading to the formation of advanced glycation end products (AGEs), are involved in the chemical modification of proteins during normal aging and have been implicated in the pathogenesis of diabetic complications. Oxidative conditions accelerate the browning of proteins by glucose, and AGE proteins also induce oxidative stress responses in cells bearing AGE receptors. These observations have led to the hypothesis that glycation-induced pathology results from a cycle of oxidative stress, increased chemical modification of proteins via the Maillard reaction, and further AGE-dependent oxidative stress. Here we show that the preparation of AGE-collagen by incubation with glucose under oxidative conditions in vitro leads not only to glycation and formation of the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML), but also to the formation of amino acid oxidation products on protein, including m-tyrosine, dityrosine, dopa, and valine and leucine hydroperoxides. The formation of both CML and amino acid oxidation products was prevented by anaerobic, anti-oxidative conditions. Amino acid oxidation products were also formed when glycated collagen, prepared under anti-oxidative conditions, was allowed to incubate under aerobic conditions that led to the formation of CML. These experiments demonstrate that amino acid oxidation products are formed in proteins during glycoxidation reactions and suggest that reactive oxygen species formed by redox cycling of dopa or by the metal-catalysed decomposition of amino acid hydroperoxides, rather than by redox activity or reactive oxygen production by AGEs on protein, might contribute to the induction of oxidative stress by AGE proteins.

Amino Acids↗
PubMed1998

Low density lipoprotein of synovial fluid in inflammatory joint disease is mildly oxidized.

Oxidatively modified low density lipoprotein (LDL) has many biological activities which could contribute to the pathology of the atherosclerotic lesion. Because atherosclerosis has an inflammatory component, there has been much interest in the extent to which LDL could be oxidatively modified in vivo by inflammation. The present study examined LDL present in an accessible inflammatory site, the inflamed synovial joint, for evidence of compositional change and oxidative modification. LDL was isolated from knee joint synovial fluid (SF) from subjects with inflammatory arthropathies and also from matched plasma samples. SF and plasma LDL had similar free cholesterol and alpha-tocopherol content, but SF LDL had a lower content of esterified cholesterol. On electrophoresis, SF LDL was slightly more electronegative than LDL from matched plasma samples, but the changes were much less than those resulting from Cu2+-treatment of LDL. Oxidized cholesterol was not detected in any samples, but cholesterol ester hydroperoxide levels were greater in SF than in plasma LDL. When samples from three subjects were incubated with macrophages, the SF LDL did not cause significant loading of the cells with cholesterol or cholesterol esters, in contrast to the situation with acetylated LDL. Overall, the SF LDL displayed evidence of slightly increased oxidation by comparison with matched plasma samples. Despite their isolation from an environment with active inflammation, changes were modest compared with those resulting from Cu2+ treatment. Thus, extensive LDL oxidation is not a necessary correlate of location in a chronic inflammatory site, even though it is characteristic of atherosclerotic lesions.

Animals↗
PubMed1998

3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation.

gamma-Irradiation of several amino acids (Val, Leu, Ile, Lys, Pro, and Glu) in the presence of O2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO* attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3-hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4-hydroxyhexanoic acid], (2S, 5R)-5-hydroxylysine [(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5-hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu-Phe) and proteins (BSA and histone H1) exposed to HO./O2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.

Amino Acids↗
PubMed1998

Alpha-tocopherol supplementation of macrophages does not influence their ability to oxidize LDL.

We have investigated the effect of alpha-tocopherol-loading of mouse peritoneal macrophages and human monocytes on their ability to oxidize human low density lipoprotein (LDL). Mouse peritoneal macrophages incorporated alpha-tocopherol (alpha-TOH) from culture medium supplemented with the vitamin in a time- and concentration-dependent manner. Subcellular fractionation by density gradient ultracentrifugation showed that the distribution of incorporated alpha-TOH within the cell was similar to that of free cholesterol. Most (approximately 88%) of alpha-TOH partitioned into the membrane fractions (plasma membrane approximately 41%, mitochondria and lysosomes approximately 26%, and endosomes plus endoplasmic reticulum approximately 21%). Cellular alpha-TOH was stable for at least 24 h in serum- or LDL-free media whether permissive (Ham's F-10) or non-permissive (Dulbecco's minimum essential medium, DMEM) for LDL oxidation. When incubated with LDL in DMEM, alpha-TOH-preloaded cells transferred small amounts of alpha-TOH (approximately 1 nmol/mg LDL protein after 9 h) to the lipoprotein. However, enrichment of the cells with alpha-TOH did not change the kinetics of oxidation of either normal or TOH-depleted LDL in Ham's F-10 medium compared with non-loaded cells, as assessed by alpha-TOH consumption, cholesteryl ester degradation, and cholesteryl ester hydroperoxide and 7-ketocholesterol accumulation. Nor did it alter superoxide release by the cells or their ability to reduce extracellular copper(II). Similar to mouse macrophages, enrichment of human monocytes with alpha-TOH did not change the kinetics of cell-mediated LDL oxidation. We conclude that elevated cellular levels of alpha-TOH in mouse peritoneal macrophages and in human monocytes do not affect their ability to oxidize LDL lipids in vitro. This suggests that either cell-mediated oxidation of LDL under the conditions of this study is not dependent on cell-derived radical species or that cellular alpha-TOH is unable to affect their formation.

Animals↗
PubMed1998

Accumulation and metabolism of low density lipoprotein-derived cholesteryl linoleate hydroperoxide and hydroxide by macrophages.

Cholesteryl linoleate hydroperoxide (CLOOH) and hydroxide (CLOH) are present in human atheroma. The intracellular metabolism of low density lipoprotein (LDL)-derived CLOOH and CLOH remain undefined because extensive free radical-mediated LDL oxidation, which modifies LDL apolipoprotein B sufficiently to allow endocytosis by the scavenger receptor (ScR), also degrades CLOOH and CLOH. This problem was approached by first acetylating LDL lysine residues (AcLDL) to achieve protein modification, then exposing AcLDL to the aqueous radical donor 2,2'-azobis(2-amidinopropane) HCl (AAPH), to generate mildly oxidized AcLDL (OxAcLDL). Murine peritoneal macrophages incubated with OxAcLDL accumulated large quantities of CE and small, non-toxic quantities of CLOOH and CLOH in a time- and concentration-dependent manner, and accumulation was inhibited by fucoidin. Inhibition of acyl CoA: cholesterol acyltransferase during loading did not inhibit the accumulation of either CLOOH or CLOH, whereas NH4Cl decreased intracellular clearance of accumulated CLOOH from 68.3 +/- 1.7% to 35.3 +/- 1.0% over 12 h, suggesting lysosomal or pre-lysosomal accumulation. Intracellular clearance of unoxidized lipoprotein-derived CE decreased from 84.0 +/- 5.9% to 43.1 +/- 2.3% over 12 h when cells were loaded with AcLDL or OxAcLDL, respectively. Aggregation of mildly oxidized LDL, even without acetylation, also promoted cellular accumulation of CLOOH and CLOH. We conclude that intracellular accumulation of cholesteryl linoleate hydroperoxide and cholesteryl linoleate hydroxide can follow charge modification or aggregation of mildly oxidized LDL, and that LDL-derived oxidation products may inhibit hydrolysis of LDL-derived CE in foam cell macrophages.

Acetylation↗
PubMed1997

Biochemistry and pathology of radical-mediated protein oxidation.

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

Animals↗
PubMed1997

Structural characterization of the products of hydroxyl-radical damage to leucine and their detection on proteins.

We have previously reported the formation of valine hydroperoxides and aldehydes from hydroxyl-radical attack on free valine and protein molecules. We have also demonstrated that the major degradation products of valine hydroperoxides by several biochemical and cellular systems are the corresponding hydroxides, and therefore proposed that hydroxyvalines may serve as useful in vivo markers for studying protein oxidation. Here we have undertaken the structural elucidation of the oxidation products of leucine, another amino acid which is very susceptible to peroxidation. Hydroxyl-radical (HO.) attack on l-leucine in the presence of oxygen, followed by NaBH4 reduction, gave rise to five major oxidation products which have been isolated and identified. On the basis of chemical and spectroscopic evidence, the five products have been identified as (2S)-gamma-hydroxyleucine, (2S,4S)-delta-hydroxyleucine, (2S,4R)-delta-hydroxyleucine, (2S,4R)-4-methylproline (trans-4-methyl-l-proline) and (2S,4S)-4-methylproline (cis-4-methyl-l-proline). The three hydroxyleucines have been confirmed to be the reduction products of the corresponding hydroperoxyleucines, while the two proline analogues are from reduction of their corresponding cyclic Schiff bases. By HPLC analysis using post-column o-phthaldialdehyde derivatization, we have detected hydroxyleucines in the hydrolysates of tripeptides and proteins which had been gamma-radiolysed and treated with NaBH4. Furthermore, we demonstrate the occurrence of the hydroxyleucines on proteins in physiological and pathological samples. Hydroxyleucines, like hydroxyvalines, may provide useful in vivo markers for studying protein oxidation. In the present study we also investigated the competition between leucine, valine and phenylalanine for HO., and proposed a possible radical-transfer process in such free-radical reactions.

Cataract↗
PubMed1997

Loading with oxidised low density lipoprotein alters endocytic and secretory activities of murine macrophages.

Lipid-loaded macrophages were produced in vitro by incubation with acetylated or copper-oxidized LDL. In order to establish whether cellular membrane traffic is generally perturbed by such loading, we assessed endocytosis of fluid; cell surface binding, internalisation and degradation of a soluble ligand and of a particulate preparation; and exocytosis of lysosmal enzymes. Fluid-phase pinocytosis of sucrose was unaffected by either form of loading. Binding, uptake and degradation of soluble (mannosylated-BSA) and particulate (zymosan) ligands by these lipid-loaded and by non-loaded cells were compared. Loading with oxidized LDL decreased the processing of both ligands, while loading with acetylated LDL had little effect. Loading with oxidized LDL (Ox-LDL) also decreased zymosan binding at 4 degrees C; and the internalisation and degradation of ligands in Ox-LDL loaded and non-loaded cells reflected the extent of surface binding. Changes in binding and uptake of mannosylated-BSA and zymosan were not due to changes in viability or cell number. Zymosan stimulated release of lysosomal beta-N-acetyl-D-glucosaminidase from the cells. Loading with Ox- but not Ac-LDL decreased beta-N-acetyl-D-glucosaminidase secretion. After incubation with zymosan, intracellular levels of the enzyme were increased in the Ox-LDL loaded cells. Zymosan uptake and beta-N-acetyl-D-glucosaminidase secretion were correlated, but enzyme activity per culture rose more in the absence than in the presence of zymosan. We conclude that membrane traffic is perturbed in model foam cells, particularly those loaded with Ox-LDL.

Acetylglucosaminidase↗