Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the mechanisms of holo-caeruloplasmin biosynthesis, we measured the serum caeruloplasmin concentration and oxidase activity, hepatic caeruloplasmin mRNA content and hepatocyte caeruloplasmin biosynthesis and secretion in normal and copper-deficient rats. Copper deficiency resulted in a near-complete loss of serum caeruloplasmin oxidase activity, yet only a 60% reduction in serum caeruloplasmin concentration and no change in the abundance of hepatic caeruloplasmin mRNA or the rate of caeruloplasmin biosynthesis. Both interleukin-1 alpha and lipopolysaccharide increased hepatic caeruloplasmin mRNA content and caeruloplasmin biosynthesis in normal and copper-deficient animals, but neither mediator increased caeruloplasmin oxidase activity in the copper-deficient group. Pulse-chase studies in primary hepatocytes from normal and copper-deficient rats revealed that the secretory rates for newly synthesized caeruloplasmin were identical, despite little or no holo-caeruloplasmin synthesis in hepatocytes of copper-deficient rats. We conclude that hepatocyte copper content has no effect on hepatic caeruloplasmin-gene expression or caeruloplasmin biosynthesis and that the incorporation of copper into newly synthesized caeruloplasmin is not a rate-limiting step in the biosynthesis or secretion of the apoprotein from rat hepatocytes.
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PMID:Mechanisms of caeruloplasmin biosynthesis in normal and copper-deficient rats. 155 68

Conditioned medium from human monocyte-macrophages incubated under various conditions was tested for its ability to stimulate fibrinogen mRNA levels in the hepatoma cell line HepG2. Recombinant human interleukin-6 (IL-6) stimulated fibrinogen mRNA levels 4.4-fold over control levels; this response was blocked by an anti-IL-6 antibody. Conditioned medium from 3-day-cultured monocyte-macrophages produced a slight stimulation of fibrinogen synthesis in HepG2 cells which was enhanced when the monocyte-macrophages had been treated with lipopolysaccharide (LPS). This stimulation was blocked by the anti IL-6 antibody. The cytokines, interleukin-1 (IL-1) and tumour necrosis factor (TNF) were also detected in the conditioned medium from the 3-day-cultured monocyte-macrophages. Monocyte-macrophages were cultured for 17 days and then incubated with acetylated low density lipoprotein (AcLDL) for 48 h. Such cells were 'foamy' in appearance and showed a 4-fold increase in apoE mRNA and a 10 to 50-fold increase in apoE secretion. This increase in apoE production was suppressed by almost a third when cells were coincubated with AcLDL and LPS. Conditioned medium from these 17-day-cultured AcLDL-treated human monocyte-macrophages did not stimulate fibrinogen mRNA synthesis in HepG2 cells, nor did the conditioned medium contain detectable levels of cytokines. These results suggest that cytokine production from foam cells in the atherosclerotic lesion is unlikely to be a major contributing factor in determining the elevated fibrinogen levels seen in the plasma of patients with IHD.
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PMID:Cytokine production by cholesterol-loaded human peripheral monocyte-macrophages: the effect on fibrinogen mRNA levels in a hepatoma cell-line (HepG2). 193 38

Administration of purified bacterial lipopolysaccharide (LPS) to male rats suppressed the constitutive hepatic expression of the male-specific cytochrome P-450 [AH, reduced flavoprotein:oxygen oxidoreductase (RH hydroxylating), E.C.1.14.14.1] isozyme P-450h (P450IIC11) to about 35% of control levels within 24 hr. The mRNA for P-450h was more rapidly and more profoundly suppressed than was the protein, indicating (a) that the decrease in the mRNA was responsible for the suppression of the protein and (b) that other mechanisms work to maintain expression of P-450h apoprotein in the face of repression of its mRNA. Suppression of P-450h expression was maximal at an endotoxin dose of 30-100 micrograms/kg, indicating that P-450 suppression is concomitant with the acute-phase response of hepatic secretory proteins. The female-specific cytochrome P-450 isozyme, P-450i (P450IIC12), was suppressed to 17% of control levels by LPS administration in female rats. Suppression of the P-450i apoprotein by LPS, and recovery of its expression, was more rapid than was suppression of P-450h in males. P-450i protein and mRNA levels were concomitantly suppressed by LPS, indicating that although there is a pretranslational component to the suppression, other mechanisms may also contribute. Calculations based on estimations of the microsomal contents of P-450h and P-450i relative to the total cytochrome P-450 in untreated rat livers indicate that suppression of these forms contributes significantly to the decreases in total microsomal P-450 after LPS treatment. In these studies, hepatic microsomal NADPH-cytochrome c reductase (TPNH2-cytochrome c reductase, E.C.1.6.2.4) activities and content of cytochrome b5 were decreased by LPS administration in both male and female rats. Like its effects on cytochrome P-450 expression, endotoxin suppression of NADPH-cytochrome c reductase activities and cytochrome b5 levels was more rapid in female rats than in males. The production of a local inflammatory response in male rats by subcutaneous injection of turpentine caused effects on cytochrome P-450, P-450h expression, and cytochrome b5 that were similar to those of endotoxin but were less rapidly achieved.
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PMID:Suppression of constitutive cytochrome P-450 gene expression in livers of rats undergoing an acute phase response to endotoxin. 251 27

Complexes of lipopolysaccharide (LPS) B of Salmonella typhimurium with human low density lipoproteins (LDL) formed during in vitro coincubation via spontaneous incorporation of LPS (complex LDL-LPS) or through the incorporation stimulated by the serum protein fraction (LPS/LDL complex) were studied. The LPS/LDL complex was shown to maximally bind 0.24 mg of LPS per 1 mg of LDL protein, whereas the LDL-LPS complex contained only 0.07 mg of LPS per 1 mg of LDL protein. The observed incorporation of LPS into LDL particles was not possibly associated with a transfer of lipids or proteins from high density lipoproteins to LDL. The insertion of LPS was probably accompanied by the expulsion of a small portion of phosphatidylcholine molecules from the outer monolayer of LDL into the aqueous medium and by an increase in the phosphatidylethanolamine concentration in LDL. Simultaneously, the level of esterified cholesterol in the LPS/LDL complex decreased, and the concentrations of free cholesterol and triacylglycerols showed a rise. The level of free fatty acids in the LPS/LDL complex increased more than twofold compared with intact LDL. The enhancement of LPS incorporation did not result in the insertion of any serum proteins into LDL, in which apoB-100 remained the major apolipoprotein (ca. 90%); apoB-100 fragments made up to 5-7%, whereas apoE and apoC contained altogether ca. 3-5%. It is suggested that the LPS/LDL complex obtained can bind to three types of cell receptors, i.e., apoB/E receptors, LPS receptors and scavenger receptors of macrophages (monocytes); the increased level of free fatty acids in the LPS/LDL complex may accelerate its subsequent catabolism.
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PMID:[Effect of lipopolysaccharide toxin on lipid and protein composition of human serum low density lipoproteins]. 266 26

Complexes of Salmonella typhimurium lipopolysaccharide toxin (LPS) with low density lipoproteins (LDL) containing various amounts of LPS were prepared in vitro. The 31P-NMR spectra showed that in the LDL-LPS complexes as well as in native LDL all phosphate groups of phospholipids are accessible to the paramagnetic shift reagent, Pr3+. Besides, the low frequency mobility of phospholipid phosphates in the complex is diminished. It was supposed that the phospholipid molecules in the LDL/LPS complex as in native LDL form a monolayer structure on the surface of LDL. The intrinsic fluorescence spectra of tryptophan residues of the apoprotein (apo B-100) revealed that the incorporation of LPS molecules into LDL particles is accompanied by minor changes in the conformation and orientation of the apo B molecule. As a result of these changes, certain fragments become exposed to a more hydrophilic environment and become more accessible to fluorescence quenchers. The use of charged (I-, Cs+) and uncharged (acrylamide) quenchers permitted to identify in the apo B molecule different tryptophan residues, some of which are localized in the vicinity of negatively charged groups, whereas others are neighbouring positively charged groups. It is suggested that the LPS molecules incorporated into LDL particle do not screen the apo B molecule to such an extent that it would hinder the LDL/LPS complex binding to apo B/E cellular receptors.
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PMID:[Structure of the lipopolysaccharide/human plasma low density lipoprotein complex. 31P-NMR and fluorescence spectroscopy studies]. 266 45

Density gradient ultracentrifugation was used to isolate and characterize the plasma lipoproteins from African green monkeys before and 24 and 48 h after subcutaneous injection of 300 micrograms/kg lipopolysaccharide (LPS) to induce an acute phase response. Compared with 0 h values, reductions occurred in plasma cholesterol (39%), high density lipoprotein (HDL) cholesterol (54%), lecithin:cholesterol acyltransferase (LCAT) activity (55%), and post-heparin plasma lipase activity (68%) 48 h after LPS injection while plasma triglyceride concentrations increased 700%. Cholesterol distribution among lipoproteins shifted from 7 to 41% in very low density lipoproteins (VLDL), 65 to 38% in low density lipoproteins (LDL), and 28 to 21% in HDL after LPS injection. At 48 h after LPS injection, all lipoprotein classes were relatively enriched in phospholipid and triglyceride and depleted of cholesteryl ester. The plasma concentration of all chemical constituents in VLDL was increased 3-9-fold within 48 h after LPS injection. By negative stain electron microscopy, HDL were discoidal in shape while VLDL and LDL appeared to have excess surface material present. Even though total HDL protein concentration in plasma was unaffected, the plasma mass of the smallest HDL subfractions (HDL3b,c) doubled while the mass of intermediate-sized subfractions (HDL3a) was dramatically decreased within 24 h after treatment. HDL became enriched in apoE, acquired apoSAA, and became depleted of apoA-I, A-II, and Cs by 48 h after LPS injection while apoB-100 remained the major apoprotein of VLDL and LDL. We conclude that administration of LPS to monkeys prevents normal intravascular metabolism of lipoproteins and results in the accumulation of relatively nascent forms of lipoproteins in plasma. These immature lipoproteins resemble those isolated from the recirculating perfusion of African green monkey livers, which are relatively deficient of LCAT activity and those isolated from the plasma of patients with familial LCAT deficiency.
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PMID:Lipoprotein abnormalities associated with lipopolysaccharide-induced lecithin: cholesterol acyltransferase and lipase deficiency. 272 68

Previous studies indicated that E. coli lipopolysaccharide (LPS) induces human umbilical vein endothelial cells (HUVEC) to express tissue factor activity. Using a radiolabeled anti-tissue factor monoclonal antibody to assess cell-surface tissue factor apoprotein antigen and a two-stage amidolytic assay to assess functional tissue factor activity, we have investigated the temporal relationship between antigenic expression and functional expression of tissue factor on the surface of LPS-stimulated HUVEC. Maximum tissue factor apoprotein antigenic expression on the surface of LPS-stimulated HUVEC was achieved in four hours after LPS treatment, while maximum functional tissue factor activity occurred after 6 hours. Specific binding of radiolabelled human factor VIIa to LPS-stimulated HUVEC paralleled the time course of the expression of tissue factor functional activity. Thus, these data indicate that the presence of of newly-synthesized tissue factor apoprotein antigen on the cell surface is insufficient by itself for maximal factor VIIa binding to occur, and provide presumptive evidence for the posttranslational processing of tissue factor apoprotein on the cell surface prior to its acquisition of ligand binding function.
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PMID:Correlation between antigenic and functional expression of tissue factor on the surface of cultured human endothelial cells following stimulation by lipopolysaccharide endotoxin. 278 22

Serum amyloid A (SAA) is a small (12 kDa) acute-phase apoprotein of high density lipoprotein found in mammals. It is also the precursor to amyloid protein A, the main protein constituent of fibrils found in amyloidosis secondary to chronic or recurrent inflammation--e.g., rheumatoid arthritis. However, rats do not develop amyloidosis and SAA is not an apoprotein of rat high density lipoprotein; thus rats appear to be an exception in regard to expression of SAA genes. We report here that rats do have representatives of the SAA gene family and express two distinct SAA mRNAs. Moreover, the pattern of genes expressed among tissues, and their induction by inflammatory agents, is similar to that of related mouse genes. RNA from various tissues of normal and injured rats was examined by RNA blot hybridization with SAA cDNA and complementary RNA probes for the three murine SAA genes. A SAA mRNA of approximately 400 nucleotides related to mouse SAA1 and SAA2 mRNAs reached a high level in liver 24 hr after injection of bacterial lipopolysaccharide. No extra-hepatic tissues were found to express the SAA1/SAA2-related mRNA. Turpentine induced two hepatic SAA1/SAA2-related mRNAs of approximately 400 and approximately 500 nucleotides in length. Liver SAA1/SAA2-related mRNA hybrid selected and translated in a wheat germ protein-synthesizing system, from lipopolysaccharide- and turpentine-injected rats, produced a single protein with an estimated molecular mass of 8 kDa. This rat liver SAA-related mRNA appears to lack a highly conserved coding region for portions of two amphipathic helical domains and the joining sequence. An mRNA related to mouse SAA3 was found expressed at a high level in lung after lipopolysaccharide but not following turpentine injection. This mRNA was also expressed at high levels in ileum and large intestine of control rats and was not found in the liver of control or challenged rats. These observations show that the SAA gene family is present and expressed in rats and that its expression is found under situations similar to those found in mice. This lends support for the importance of the SAA gene family in the response to injury by vertebrates.
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PMID:Rat tissues express serum amyloid A protein-related mRNAs. 292 11

The serum amyloid protein (apo-SAA) is a unique high density lipoprotein apoprotein exhibiting dramatic increases in plasma concentration following host injury. The events involved in the secretion of apo-SAA and assembly of apo-SAA-rich lipoprotein particles were studied in primary, serum-free culture of adult BALB/c mouse hepatocytes harvested 3 h following administration of the potent apo-SAA inducer, bacterial endotoxin (50 micrograms of intraperitoneally administered Salmonella typhosa lipopolysaccharide). An approximately 3.5-fold increase in the initial rate of apo-SAA secretion was observed over that of hepatocytes isolated from control mice, whereas the rate of apo-A-I secretion was unchanged by endotoxin administration. Sodium dodecyl sulfate-gel electrophoresis and autoradiography of [35S]methionine-labeled cell products indicated the synthesis of both major mouse apo-SAA isotypes by hepatocytes. Essentially all of the secreted apo-SAA chromatographed in Sephadex G-150 with an elution volume corresponding to a molecular weight of approximately 12,000. Approximately 90% of the secreted apo-SAA was recovered in fractions (d greater than 1.21 g/ml) following ultracentrifugal fractionation. In media supplemented with human lipoproteins (100 micrograms/ml), approximately 50% of the secreted apo-SAA was recovered in the high density lipoprotein fraction. These results suggest that mouse apo-SAA is secreted in monomeric form and becomes associated with lipoproteins in the intravascular compartment.
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PMID:Secretion of serum amyloid protein and assembly of serum amyloid protein-rich high density lipoprotein in primary mouse hepatocyte culture. 680 50

Bacterial endotoxin is a potent inducer of the serum amyloid protein (apo-SAA), a high density lipoprotein (HDL) apoprotein. In a study of the induction of apo-SAA and the structure of apo-SAA-rich lipoprotein particles in mice, we have observed that, following intraperitoneal administration of Salmonella typhosa lipopolysaccharide (50 micrograms), plasma apo-SAA levels rose from base-line levels of less than 1% to greater than 20% of the HDL protein content at 20 h postinjection. No changes in the relative content of other HDL apoproteins were noted; analysis of apo-SAA-rich HDL lipid content indicated a significant decrease (10%) in phospholipid content relative to that of control HDL. Two major apo-SAA isotypes, apo-SAA1 and apo-SAA2, were identified, having apparent molecular weights of 12,600 and 11,800, respectively, and isoelectric points of 6.35 and 6.20, respectively. Quantitative immunoprecipitation experiments indicated that essentially all of the apo-SAA was bound to lipoprotein particles containing apo-A-I. Apo-SAA was distributed among higher density HDL subfractions than were other HDL apoproteins following density gradient centrifugation, and subfractions having apo-SAA:apo-A-I molar ratios of greater than 2:1 were identified. These results indicate the formation of a subset of apo-SAA-rich HDL particles following apo-SAA induction by endotoxin.
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PMID:Changes in high density lipoprotein content following endotoxin administration in the mouse. Formation of serum amyloid protein-rich subfractions. 710 14


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