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)

The effect of LPSw (a lipopolysaccharide from wheat flour) on cholesterol catabolism was examined using WHHL (Watanabe heritable hyperlipidemic) rabbit, which is an experimental model of familial hyperlipidemia. The serum cholesterol level of the animal decreased by the addition of LPSw to drinking water. Following cessation of the addition of LPSw to the drinking water, the cholesterol level was decreased for 30 to 40d and then gradually elevated. The serum level of apolipoprotein B, which is a constituent of apolipoprotein of low density lipoprotein (LDL), also decreased in accord with serum cholesterol at a nearly coincident rate. Conversely, the level of apolipoprotein A-I, which is a constituent of apolipoprotein of high density lipoprotein (HDL), did not change, nor did HDL-cholesterol. Furthermore, the atherosclerosis risk factor, expressed as the ratio of apolipoprotein B to apolipoprotein A-I, was decreased by LPSw administration.
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PMID:Homeostasis as regulated by activated macrophage. VII. Suppression of serum cholesterol level by LPSw (a lipopolysaccharide from wheat flour) in WHHL (Watanabe heritable hyperlipidemic) rabbit. 139 46

Tissue factor (TF) which initiates clotting process can be expressed by stimulated endothelial cells (EC). TF is an apolipoprotein requiring an association with phospholipids (PL) in order to become active. Also PL constitute an important storage pool of polyunsaturated fatty acids (PUFAs) in EC which can be modulated by diet or cell medium supplementation. In order to test the effect of such manipulation upon TF activity, we have pre-enriched human EC cultures with different fatty acids of nutritional interest. TF was evaluated after 4 h of thrombin stimulation by using a chromogenic method. Without additional stimulating agents, these acids have no effect on the basal level of TF. Eicosapentaenoic and docosapentaenoic acids appeared to be ineffective at the stimulated TF level. Only adrenic acid (22:4(n-6)) has been found to significantly enhance TF activity of thrombin-stimulated endothelial cells. Other TF inducers were also tested after 22:4(n-6) enrichment. An increase tendency of TF expression was found only with tumor necrosis factor, whereas interleukin-1 beta, lipopolysaccharide and especially phorbol myristate acetate stimulations were not significantly modified. The priming effect of adrenic acid on thrombin stimulated TF expression might involve alterations of signal transduction pathways rather than modifications of apolipoprotein III environment. Adrenic acid, which is a prostacyclin inhibitor, appears to be potential prothrombotic agent.
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PMID:Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells. 164 92

Serum amyloid A (SAA) is a plasma apolipoprotein produced by the liver in response to inflammatory stimuli. The murine SAA gene family is made up of three genes, SAA1, SAA2, and SAA3, plus a pseudogene. The SAA1 and SAA2 genes are highly homologous while the SAA3 gene has diverged substantially from the other two genes. Using small fragments from the cloned genes, we have analyzed the expression of each gene in the SAA family. Within 12 h after endotoxin administration, total liver SAA mRNA increases by 2000-fold, reaching approximately 20,000 transcripts/cell. Each gene accounts for approximately one-third of total SAA mRNA transcripts at this time. The increase is specific, since the levels of the mRNAs encoding albumin and apolipoprotein A-I in liver decrease 2-fold by 24 h. This correlates with a 2-fold decrease of the serum concentrations of these two proteins as well as their in vitro protein synthesis in primary hepatocytes. SAA1+2 mRNAs maintain their maximum levels until 36 h after lipopolysaccharide administration, while SAA3 mRNA is degraded to 20% its maximal level. As assayed by in vitro transcription in isolated hepatocyte nuclei, total SAA gene transcription increases at least 300-fold during the inflammatory response. The transcription rates of the individual SAA genes are similar during the initial stages of this response, reaching peak levels at 3 h. A comparison of the rates of SAA gene transcription and SAA mRNA accumulation suggests that SAA mRNA levels are regulated during the acute phase response by increased transcription and mRNA stabilization.
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PMID:Transcriptional regulation of serum amyloid A gene expression. 242 96

Complexes of Salmonella typhimurium lipopolysaccharide toxin (LPS) with low density lipoproteins (LDL) prepared in vitro have been analyzed. LPS-LDL complexes were found to comprise approx. 0.24 mg LPS/mg LDL protein. The major protein of complexes was apolipoprotein apoB-100 (greater than or equal to 90-95%). Incorporation of LPS molecules into LDL was accompanied by small changes in lipid composition, i.e. the phosphatidylcholine content was diminished by approx. 11% and the free fatty acid concentration was raised 2-fold. Analytical ultracentrifugation showed that insertion of LPS into LDL results in the increase of a portion of particles with higher density (lower flotation coefficient) compared to initial LDL. As was evidenced by ESR, in LPS-LDL complexes, the phospholipid hydrocarbon chains are more ordered than in LDL. 31P-NMR spectra indicated that in LPS-LDL complexes the mobility of phospholipid polar headgroups is restricted in comparison with LDL. Application of the shift reagent (Pr3+) revealed that phospholipid molecules form a monolayer structure on the surface of complexes. Upon binding of LPS to LDL, a maximum of the apoB intrinsic fluorescence was slightly red-shifted (1-2 nm) which may testify that the localization of apoB remains nearly unchanged. For LPS-LDL complexes, the accessibility of apoB fluorophores to quenchers (I-, Cs+, acrylamide) did not dramatically differ from that of LDL. It is concluded that rather large amounts of LPS (about 9-10 molecules) can accommodate in one LDL particle without severely perturbing its original composition and structure. Moreover, in the LPS-LDL complexes, oligosaccharide chains of LPS screen notably neither phospholipid polar headgroups nor, what is very important, apoB. LPS-LDL complexes are suggested to be able in vivo to bind to cellular apoB/E receptors, possible LPS receptors and scavenger-receptors of macrophages (monocytes).
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PMID:Composition and structure of lipopolysaccharide-human plasma low density lipoprotein complex. Analytical ultracentrifugation, 31P-NMR, ESR and fluorescence spectroscopy studies. 254 21

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

The interaction of lipopolysaccharide binding protein (LBP) with apolipoprotein (apo)A-I on high density lipoproteins (HDL) was studied in solid phase ligand binding assays with a biotinylated LBP-specific antibody. The association was dependent on LBP concentration and enhanced in the presence of lipopolysaccharide (LPS). Maximal enhancement was measured at an LPS/LBP molar ratio of 6. To identify regions on apoA-I that participate directly or indirectly in the interaction between LBP and HDL, we attempted to inhibit LBP association with a panel of mapped apoA-I-specific monoclonal antibodies. Whereas some antibodies were effective inhibitors, others were not, even though they bound apoA-I. Furthermore, selected apoA-I synthetic peptides inhibited the antibody-mediated interference of the HDL/LBP interaction. Although no specific mechanism can be defined for the basis of the inhibitory effects of the antibodies on the association of LBP with HDL, we identified a role for three unique regions on apoA-I between residues 1-31, 95-164, and 178-200. These results suggested that apoA-I is a key component in the association of LBP with HDL and may play an important role in the biologic activity of LPS/LBP complexes.
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PMID:Structural determinants for the interaction of lipopolysaccharide binding protein with purified high density lipoproteins: role of apolipoprotein A-I. 910 32

Apolipoprotein E (apoE) is a 299 amino acid protein with multiple biological functions. Initially described in the context of cholesterol metabolism, apoE also has immunomodulatory properties and recent evidence has implicated a role for apoE in neurological disease. One possibility is that apoE, which is the predominant apolipoprotein produced intra-axially, may modify the CNS response to acute and chronic injury. We prepared mixed neuronal-glial cultures from apoE deficient mouse pups and measured secretion of TNF alpha after stimulation with lipopolysaccharide (LPS) in the presence and absence of human recombinant apoE3 and E4. We demonstrate that preincubation with apoE blocks glial secretion of TNF alpha in a dose-dependent manner. This effect is independent of any direct effect of apoE on cell viability and is greatest when apoE is preincubated with the cell culture for 24 h.
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PMID:Apolipoprotein E suppresses glial cell secretion of TNF alpha. 918 34

The human apolipoprotein (apo) E4 isoform is associated with an increased risk for Alzheimer's disease (AD) and poor prognosis after acute CNS injury. Addition of human apoE inhibits murine microglial activation in culture, suggesting that microglia might be an important physiological target of apoE. In the present study, we examined the role of endogenous murine apoE in modulating microglial nitric oxide (NO) production following lipopolysaccharide (LPS) stimulation. Brain cultures from apoE-deficient mouse pups showed enhanced NO production relative to cultures from wild-type mice and from transgenic mice expressing the human apoE3 isoform, demonstrating that endogenous apoE produced by glial cultures is capable of inhibiting microglial function. ApoE produced within the brain may suppress microglial reactivity and thus alter the CNS response to acute and chronic injury.
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PMID:Endogenous apolipoprotein E suppresses LPS-stimulated microglial nitric oxide production. 955 26

We recently reported a positive correlation of the pool size of lipopolysaccharide receptor (CD14)dim and Fc gamma receptor IIIa (CD16a)+ monocytes in peripheral blood to the apolipoprotein E4 (apoE4) phenotype and a negative correlation to high density lipoprotein (HDL) cholesterol levels (Arterioscler Thromb Vasc Biol. 1996;16:1437-1447). In this study, the in vitro differentiation of mononuclear phagocytes derived from healthy blood donors homozygous for the E3/3 or the E4/4 phenotype was analyzed during 7 days of culture in serum-free medium supplemented with macrophage colony-stimulating factor (M-CSF). The CD16a expression, which indicates Fc receptor-dependent phagocytic activity, increased to a significantly higher level in apoE4/4 monocytes than in apoE3/3 cells. The costimulatory molecule CD40, which indicates antigen-presenting capacity, was upregulated more strongly in apoE3/3 monocytes compared with E4/4 cells, but the difference did not reach a significant level. The expression of differentiation-associated surface proteins (CD14, CD33, CD45) and adhesion molecules (CD11a, CD11b, CD11c, CD49d) was not significantly different between apoE3/3 and apoE4/4 monocytes. However, a significantly decreased intracellular apoE concentration and a reduced amount of secreted apoE were found in apoE4/4 monocytes during in vitro differentiation. No differences were found in the surface expression of the low density lipoprotein receptor-related protein (CD91) and the uptake of fluorescence labeled low density lipoprotein between apoE3/3 and apoE4/4 monocytes. These data indicate that the apoE4/4 phenotype significantly influences the M-CSF-dependent differentiation of monocytes toward a more CD16a-positive phagocytic phenotype.
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PMID:Enhanced upregulation of the Fc gamma receptor IIIa (CD16a) during in vitro differentiation of ApoE4/4 monocytes. 974 31

Several factors that increase the likelihood of developing Alzheimer's disease (AD) have already been identified. A correct evaluation of these may contribute to a better understanding of the etiology of the disease. The risk of developing AD definitely increases with (a) age, (b) head injuries, (c) family history of AD or Down syndrome, (d) sex (higher prevalence of AD in women), (e) vascular disease, (f) exposure to environmental toxins, (g) infectious processes, or (h) changes in immune function, and recent advances in molecular genetics have suggested that genetic predisposition (i) can be considered one of the most important risk factors in the development of AD. A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (ApoE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of ApoE. A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with amyloid plaques. It has become evident that a dysregulation of cytokine release appears within lesions of many types of brain disorders including infection, trauma, stroke, and neurodegenerative diseases. Many studies have shown that microglia secrete both cytokines and cytotoxins and since reactive microglia appears in nearly every type of brain damage, it is likely that their secreted products ultimately help to determine the rate of damaged brain tissue. In this study, in vitro cell cultures were established to investigate the effect of different concentrations of human sera (2.5% and 10%) with specific ApoE genotypes from Alzheimer's and non-Alzheimer's subjects on ameboid and flat microglial cells obtained from neonatal rat hippocampi. Results show that a modulation in the proliferation and activation of microglial cells was obtained and that AD sera, mainly in the ApoE 3/4 and 4/4 genotype contain factor(s) which are able to induce morphological changes, as measured by an increase in the ameboid cell type. In addition, major histocompatibility complex (MHC) class II antigen expression, as measured by flow cytometric analysis, and interleukin-1beta (IL-1beta) release as measured by enzyme linked immunoadsorbent assay (ELISA), in comparison with control groups and lipopolysaccharide (LPS)-treated cells, clearly demonstrate a direct effect of ApoE 3/4 and 4/4 and/or an indirect effect mediated by the release of IL-1beta on microglia activation. These results strongly suggest that primary in vitro microglial cell cultures can be used as a screening model to test human sera as well as the effect of new potential drugs aimed at down-regulating microglia activation.
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PMID:Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes. 982 64


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