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)

Natural and synthetic adjuvants of microbial origin were compared for their capacity to potentiate the induction of experimental autoimmune thyroiditis (EAT) with the autoantigen mouse thyroglobulin (MTg). Regardless of the immunomodulator used, severe thyroiditis was observed only in EAT-susceptible strains of the k haplotype and not in EAT-resistant strains of the d haplotype. Compared to phenol-extracted lipopolysaccharide, a potent adjuvant for enhancing EAT induction, phthalyl-substituted, detoxified lipopolysaccharide, even at doses 15- to 50-fold greater, led to only low anti-mouse thyroglobulin titers and mild thyroid infiltration. The synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and three of its analogs, N-acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl-D-glycerol mycolate (MDP-L-Ala-Glyc-Myc), N-acetylmuramyl-L-alanyl-D-glutamyl-(decyl)methyl ester [MDP(decyl)methyl], and N-acetylmuramyl-L-alanyl-D-glutamine-alpha n-butyl ester [MDP-(Gln)-OnBu], designated murabutide, were tested in incomplete Freund adjuvant or in saline. In incomplete Freund adjuvant, MDP-L-Ala-Glyc-Myc was inefficient in inducing EAT, murabutide induced very mild involvement, and MDP and, more so, MDP(decyl)methyl were active but to a lesser degree than CFA. When saline was used, low levels of thyroid infiltration were observed in a few of the MDP-treated animals in only one experiment, whereas no lesions were observed when murabutide was used.
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PMID:Effects of natural or synthetic microbial adjuvants on induction of autoimmune thyroiditis. 383 8

Hemagglutinin (HAin) of Fusobacterium necrophorum was separated from the bacterial cells by trypsinization-sonication, and purified by the gel filtration on Sephadex G-100 column. The final product obtained from gel filtration gave one precipitin line in the immunodiffusion gel and produced a single band in polyacrylamide gel electrophoresis. The molecular weight of the HAin was estimated to be about 19000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was heat labile and comparatively rich in alanine, glutamine and histidine. Electron microscopy observation revealed that the HAin was a filamentous rod with 0.5-1.0 nm width or frequently showed a cluster form. The hemagglutinability was inhibited by addition of albumins but not by sugars and lipopolysaccharide. Anti HAin rabbit serum inhibited hemagglutination.
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PMID:Purification and partial characterization of Fusobacterium necrophorum hemagglutinin. 644 9

The basis for the accelerated hepatic utilization of glutamine that occurs during endotoxemia was investigated. In rats treated with Escherichia coli lipopolysaccharide, glutaminase activity, measured in membranes of freezed-thawed liver mitochondria, was unchanged compared with that of controls. However, flux through glutaminase in intact mitochondria was increased more than 3.5-fold by the endotoxin treatment. The effect was associated with an increase in the sensitivity of glutaminase flux to phosphate, an activator of the enzyme. These findings are similar to the activation of glutaminase by glucogenic hormones. We, therefore, propose that the increased hepatic consumption of glutamine during endotoxemia is due to an activation of glutaminase that is only evident in intact mitochondria.
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PMID:Activation of hepatic glutaminase in the endotoxin-treated rat. 763 40

The effects of endotoxin on the activities of the major Na(+)-independent amino acid transporters in rat liver (Systems n, asc, L, bo,+, and y+) were studied using using hepatic plasma membrane vesicles (HPMVs). Rats were treated with a single dose of Escherichia coli endotoxin (E. coli lipopolysaccharide 0127:B8 (LPS), 7.5, 15, or 30 mg/kg BW) and HPMVs were prepared by Percoll density gradient centrifugation at various timepoints after LPS administration. Vesicle purity and integrity was established by assay of enzyme markers and identical equilibrium uptakes. The activities of the Na(+)-independent amino acid transport systems y+ and bo,+ (arginine), asc (alanine and cysteine), L (leucine), and n (glutamine) were evaluated by measuring the uptake of radiolabeled amino acids using a rapid mixing/filtration technique. Amino acid uptake by HPMVs consisted of saturable and nonsaturable components. Prior treatment with endotoxin did not alter the activities of Systems n, asc, or L but resulted in a time- and dose-dependent stimulation of saturable arginine transport. Arginine transport increased within 2 h of LPS administration and exhibited a return towards basal levels by 24 h. Nonsaturable uptake (diffusion) in HPMVs was unaltered by LPS treatment. Kinetic analysis of arginine transport demonstrated the presence of both a high affinity and a low affinity carrier. Treatment with LPS resulted in a 73% increase in the Vmax of the high affinity carrier (System y+) and a 25% increase in the Vmax of the low affinity transporter (System bo,+). The data indicate selective stimulation of Na(+)-independent arginine transport in the liver during endotoxemia which may serve to support important arginine-dependent pathways during sepsis.
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PMID:Hepatic Na(+)-independent amino acid transport in endotoxemic rats: evidence for selective stimulation of arginine transport. 774 45

Uptake of radiolabelled L-arginine was studied in four different kinds of glial cultures, in astroglia-rich primary cultures derived from neonatal rat and mouse brains, in pure murine astrocyte cultures, and in rat glioma cells C6-BU-1. A saturable component of uptake was found in all cases with KM values between 15 and 35 microM and Vmax values between 0.8 and 2.5 nmol.min-1.(mg protein)-1. In addition, in all cell types a non-saturable component dominated total uptake at high concentrations of extracellular arginine. Rates of uptake of arginine were not affected when Na+ or Cl- were absent from the incubation buffer. Carrier-mediated uptake of arginine was reduced by depolarizing concentrations of K+ and strongly inhibited by an excess of lysine or ornithine. Histidine, asparagine, glutamine, citrulline, creatine, NG-nitro-L-arginine, NG-monomethyl-L-arginine, or L-canavanine inhibited L-arginine transport to various degrees. Uptake of arginine was not reduced in the presence of serine or alanine cysteic acid, N-methyl-alpha-aminoisobutyric acid, or 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid. Rates of uptake of arginine were increased when cells had been preloaded with lysine. Preincubation of primary cultures, but not glioma cells, with bacterial lipopolysaccharide stimulated transport of arginine by increasing the Vmax value of uptake. This stimulation was dependent on protein synthesis. The results suggest that, at physiological concentrations, arginine is taken up into the glial cells with the help of the transport system "y+" for basic amino acids. In glial primary cultures, uptake of arginine appears to be regulated by compounds which also exert influence on nitric oxide synthesis.
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PMID:Transport of L-arginine in cultured glial cells. 796 30

Oct2-isoform expression in splenic B cells stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning. The frequency of Oct2-positive clones was 1/15,000 in both libraries. Two new isoforms were found that generate novel amino- or carboxy-terminal sequences. An isoform lacking exon 11 destroyed the carboxy-terminal leucin-zipper region and introduced a frame shift creating a novel, proline-rich carboxy terminus. A new exon containing a highly basic region (4c) was characterized, between exons 4 and 5. This exon was inserted between glutamine-rich regions 2 and 3, carboxy terminal of a tentative leucine-zipper structure. In addition, a new combination isoform containing Oct2a's amino terminal insert (exon 7a) and Oct2b's carboxy terminal insert (exon 13) was found that created a novel large isoform, Oct2ab. More frequent use of the classical Oct2a and Oct2b isoforms was observed in the lipopolysaccharide-stimulated B cells, while a preference for the Oct2ab and Oct2ba isoforms was observed in lipopolysaccharide plus phorbol-di-butyrate-treated cells.
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PMID:Analysis of Oct2-isoform expression in lipopolysaccharide-stimulated B lymphocytes. 800 71

Interleukin-1 (IL-1) may be involved in gut permeability to macromolecules and gut glutamine metabolism during endotoxemia. We developed a sensitive radioimmunoassay specific for mouse IL-1 alpha (detection limit of 100 pg/ml, or 5 pM) and measured intestinal levels of IL-1 alpha in response to endotoxin. CD-1 mice (N = 190) were randomized to intraperitoneal (ip) or intravenous (i.v.) lipopolysaccharide (LPS) infusion (15 micrograms/g or 1.5 micrograms/g Escherichia coli 0111:B4 LPS) or saline. Mice were sacrificed at Time 0, 30 min, 1 hr, 2.5 hr, 4 hr, 6 hr, 12 hr, and 24 hr (3 mice/group/time point). Small bowel (SB) and large bowel (LB) were harvested and compared to liver. Duodenum, upper jejunum, midjejunum, terminal ileum, cecum, ascending colon, and sigmoid were analyzed in separate experiments. Tissues were frozen, weighed, and homogenized, the homogenates were centrifuged, and the supernates were assayed for immunoreactive IL-1 alpha. IL-1 alpha was expressed as pg/g wt +/- SEM (lowest detectable amount = 1000 pg/g wet tissue (WT)). SB but not LB from normal controls had constitutively elevated levels of IL-1 alpha (6177 +/- 1640 pg/g WT). LPS ip or i.v. produced lethargy, diarrhea, and a dramatic elevation of IL-1 alpha levels in both SB and LB. In SB, IL-1 alpha was elevated compared to baseline at 1 hr (19201 +/- 626 pg/g WT) and reached a fivefold maximal increase at 2.5 hr (31775 +/- 503 pg/g WT) following 15 micrograms/g ip.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal production of interleukin-1 alpha during endotoxemia in the mouse. 841 68

During septic states efflux of glutamine from the lung increases, a response sustained by an increase in glutamine synthetase (IGS) activity. We have used a cell culture model employing a rat epithelial cell line of pulmonary origin (L2 cells) to study the effect of several hormones and cytokines which mediate the septic shock response on GS expression. We found that GS mRNA and GS protein contents increased rapidly and severalfold in response to physiologically relevant levels of the synthetic glucocorticoid dexamethasone (Dex). In contrast, GS expression was not markedly induced by Escherichia coli lipopolysaccharide (LPS), cytokines, activated complement C5a, or prostaglandins. Dex did not alter the kinetics of GS mRNA decay in the presence of actinomycin D. The increase in GS mRNA in response to Dex was completely blocked by RU-38486 and by actinomycin D, but not by cycloheximide (CHX). CHX together with Dex caused a superinduction of GS mRNA. GS mRNA decay kinetics suggested that this superinduction is at least in part caused by an approximately twofold increase in GS mRNA half-life caused by CHX. In addition, actinomycin D was found to increase GS mRNA half-life by approximately 50%. Actinomycin D plus CHX acted synergistically to cause a profound inhibition of GS mRNA decay. Our results are consistent with regulation of lung GS expression via a direct glucocorticoid receptor-mediated response. In addition, GS mRNA decay in L2 cells seems to be regulated by two independent mechanisms, one which is sensitive to CHX and one which is sensitive to actinomycin D.
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PMID:Glucocorticoids regulate glutamine synthetase expression in lung epithelial cells. 877 37

Malnutrition is a common problem in elderly people. The association of malnutrition and physical illness or injury leads to both localized and general complications. In particular, impairment of the adaptive response of pancreatic function to undernutrition and refeeding may adversely affect nutritional status and elicit morbidity and mortality. Aged rats (24 mo old) were treated with lipopolysaccharide (LPS) from E. Coli (3 mg/kg body weight). Six days later, survivors were randomized to receive, for 7 days, an oral chow diet enriched with either a pancreatic extract (PE) (2.4 mg/day) or an isonitrogenous supply of casein (CAS). Endotoxemia induced a catabolic state, with a body weight loss of 7.6 +/- 1.1% on day two after LPS treatment. Mean food intake from day 6 to day 13 was similar in LPS-PE and LPS-CAS groups (19.0 +/- 5.6 versus 19.7 +/- 6.9 g). The metabolic response varied according to the type of muscle studied. In fast (white) muscle, the protein content and the glutamine pool remained markedly depleted in endotoxemic rats receiving casein supplementation. In contrast, enrichment of nutrition with PE significantly limited the LPS-induced muscle wasting and increased the muscle glutamine content. As in previous observations, no significant change occurred in slow (red) muscle. These results could indicate that PE supplementation counteracts pancreatic deficiency caused by aging and worsened by stress and this, in turn, could improve the efficiency of nutrition, to support the hypermetabolism of aged injured rats.
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PMID:Supplementation of oral nutrition with pancreatic enzymes improves the nutritional status of aged endotoxemic rats. 879 23

Simple tandem repeats of the trinucleotide sequence CAG encode homopolymeric stretches of glutamine. Although polyglutamine has been identified in diverse proteins, it is present predominantly in transcription factors. We observed that oncogene-immortalized mouse macrophages express several genes that contain a CAG repeat motif. Therefore, we attempted to clone a novel gene that contains a CAG repeat and is associated with cytokine activation of macrophages. Screening of a mouse macrophage cDNA library with a probe comprising 12 consecutive CAG triplets identified at least one unique clone. The cDNA encodes a protein (named GRP-1 or glutamine repeat protein-1) with 171 amino acids, a calculated molecular mass of 21.6 kDa, and a predicted pI of 10.67. Greater than two-thirds of GRP-1 are only two amino acids, namely glutamine (50%) and histidine (18%). There are four polyglutamine motifs interspersed with histidine-rich regions. There is also a putative nuclear localization signal flanked by sites for possible serine phosphorylation. GRP-1 mRNA was expressed constitutively in some macrophage cell lines and B and T cell lines. Interferon-gamma or lipopolysaccharide augmented GRP-1 mRNA expression in the mouse macrophage cell line ANA-1. Western blot analyses using an antipeptide serum revealed that GRP-1 was localized in the nucleus of ANA-1 macrophages and transfected 3T3 fibroblasts. Overexpression of GRP-1 decreased Sp1-driven chloramphenicol acetyltransferase gene expression in transient cotransfection experiments. Because polyglutamine motifs can cause protein oligomerization and can function as transcriptional activation domains, we suggest that GRP-1 may be a transcription factor associated with interferon-gamma- or lipopolysaccharide-induced activation of macrophages.
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PMID:Molecular cloning and characterization of a novel mouse macrophage gene that encodes a nuclear protein comprising polyglutamine repeats and interspersing histidines. 881 Mar 23


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