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)

A recombinant of toxic shock syndrome toxin 1 (TSST-1) which contains a single histidine-to-alanine mutation at residue 135 (H135A) was analyzed for toxicity and vaccine potential in a lipopolysaccharide (LPS)-potentiated mouse lethality model. The 50% lethal dose (LD50) of TSST-1 in BALB/c mice was 47.2 micrograms/kg, but H135A was not lethal when tested at a dose equivalent to 10 LD50s of TSST-1. Levels of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) in serum were, respectively, 10- and 50-fold higher in LPS-potentiated mice injected with 15 LD50s of TSST-1 than in mice given H135A. Mice injected with only TSST-1 did not have elevated levels of TNF or IFN-gamma in serum, while H135A plus LPS or LPS alone elicited identical, yet very low, levels of TNF and IFN-gamma. An enzyme-linked immunosorbent assay of H135A and TSST-1 with anti-TSST-1 serum yielded very similar dose-response curves, which strongly suggests that H135A serologically and conformationally resembles the native toxin. Mice immunized with H135A developed antibodies that recognized TSST-1 in an enzyme-linked immunosorbent assay and afforded protection against a 15-LD50 challenge of TSST-1 plus LPS. The pooled sera of mice immunized with either TSST-1 or H135A also prevented lymphocyte proliferation due to TSST-1.
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PMID:Biological activity of toxic shock syndrome toxin 1 and a site-directed mutant, H135A, in a lipopolysaccharide-potentiated mouse lethality model. 789 Mar 77

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

The involvement of hypothalamic histaminergic neurons in the mediation of the ACTH and beta-endorphin (beta-END) response to lipopolysaccharide (LPS) endotoxin was investigated in conscious male rats. LPS stimulated the release of ACTH and beta-END dose-dependently and increased the hypothalamic concentration of the histamine (HA) metabolite tele-methylhistamine significantly and that of HA slightly, indicating an increased turnover of neuronal HA. Pretreatment with the HA synthesis inhibitor alpha-fluoromethyl-histidine administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) inhibited the ACTH and beta-END response to LPS about 60%, whereas i.p. administration of the H3 receptor agonist R(alpha)methylHA, which inhibits HA synthesis and release, decreased the response about 50%. Pretreatment with the H1 receptor antagonist mepyramine (67 micrograms x 2 i.c.v.) inhibited the hormone response to LPS about 50%, while pretreatment with equimolar doses of the H2 receptor antagonists cimetidine (67 micrograms x 2 i.c.v.) or ranitidine (83 micrograms x 2 i.c.v.) had no effect on the LPS-induced release of ACTH and beta-END. When the H1 receptor antagonists mepyramine and cetirizine were administered i.p. in doses (10 mg/kg) which penetrate the blood-brain barrier the hormone response to LPS was inhibited 50% and 30%, respectively. Administered i.p. the H2 receptor antagonists had no effect on the hormone response to LPS. We conclude that hypothalamic histaminergic neurons in rats are involved in the mediation of the ACTH and beta-END response to LPS stimulation via activation of central postsynaptic H1 receptors.
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PMID:Role of hypothalamic histaminergic neurons in mediation of ACTH and beta-endorphin responses to LPS endotoxin in vivo. 796 82

Histatins are histidine-rich polypeptides secreted in human saliva. They were found to inhibit lipopolysaccharide (LPS)-mediated gelation of Limulus amoebocyte lysate, and to reverse the anti-complement action of LPS or lipid A. Histatins also gave precipitate bands in agarose gels with various LPS. The results indicate that histatins neutralized the activity of LPS by binding to the lipid A moiety of LPS.
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PMID:Anti-lipopolysaccharide activity of histatins, peptides from human saliva. 827 32

We have previously described the isolation and initial characterization of functionally distinct 15-kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind with high affinity to Escherichia coli and modulate the antibacterial actions of other leukocyte proteins on this Gram-negative bacterium. We now report the cloning and sequencing of two distinct cDNAs from a rabbit bone marrow library that encode p15s differing at only 2 residues (His-3, Arg-88 versus Arg-3, Trp-88). Tryptophan-directed chemical cleavage of two isoforms purified from a single rabbit confirms the existence of multiple isoforms with distinct function and primary structure in a single rabbit. The p15 cDNAs encode putative signal sequences and studies of cellular and subcellular localization indicate that the p15s are granule-associated proteins of PMN. Both purified isoforms bind avidly to lipopolysaccharide (LPS), the major component of the Gram-negative bacterial outer membrane. Analysis of the deduced primary structures of the p15s reveals homology to three other leukocyte proteins: CAP-18, an 18-kDa LPS-binding protein from rabbit PMN, pro-indolicidin, a 16-kDa precursor of an antibacterial peptide of bovine PMN, and cathelin, an 11-kDa cysteine protease inhibitor from porcine leukocytes, suggesting the existence of a novel family of leukocyte proteins with LPS-binding, antimicrobial, and protease-inhibitory activities.
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PMID:Antibacterial 15-kDa protein isoforms (p15s) are members of a novel family of leukocyte proteins. 844 63

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

Twenty-eight human isolates of Escherichia coli from Argentina and Spain and eight veterinary isolates received from the Ministry of Agriculture Fisheries and Foods in the United Kingdom required 2 to > 128 micrograms of ciprofloxacin per ml for inhibition. Fragments of gyrA and parC encompassing the quinolone resistance-determining region were amplified by PCR, and the DNA sequences of the fragments were determined. All isolates contained a mutation in gyrA of a serine at position 83 (Ser83) to an Leu, and 26 isolates also contained a mutation of Asp87 to one of four amino acids: Asn (n = 14), Tyr (n = 6), Gly (n = 5), or His (n = 1). Twenty-four isolates contained a single mutation in parC, either a Ser80 to Ile (n = 17) or Arg (n = 2) or a Glu84 to Lys (n = 3). The role of a mutation in gyrB was investigated by introducing wild-type gyrB (pBP548) into all isolates; for three transformants MICs of ciprofloxacin were reduced; however, sequencing of PCR-derived fragments containing the gyrB quinolone resistance-determining region revealed no changes. The analogous region of parE was analyzed in 34 of 36 isolates by single-strand conformational polymorphism analysis and sequencing; however, no amino acid substitutions were discovered. The outer membrane protein and lipopolysaccharide profiles of all isolates were compared with those of reference strains, and the concentration of ciprofloxacin accumulated (with or without 100 microM carbony cyanide m-chlorophenylhydrazone [CCCP] was determined. Twenty-two isolates accumulated significantly lower concentrations of ciprofloxacin than the wild-type E. coli isolate; nine isolates accumulated less then half the concentration. The addition of CCCP increased the concentration of ciprofloxacin accumulated, and in all but one isolate the percent increase was greater than that in the control strains. The data indicate that high-level fluoroquinolone resistance in E. coli involves the acquisition of mutations at multiple loci.
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PMID:Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. 889 Nov 48

Extracellular proteases of Porphyromonas gingivalis specific for arginyl peptide bonds are considered to be important virulence factors in periodontal disease. In order to determine the number, inter-relationship and kinetic properties of these proteases, extracellular enzymes with this peptide-bond specificity were purified and characterized from P. gingivalis W50. Three forms, which we denote RI, RI-A and RI-B, accounted for all of the activity in the supernatant. All three enzymes contain an alpha chain of approximately 54 kDa with the same N-terminal amino acid sequence. RI is a heterodimer of non-covalently linked alpha and beta chains which migrate to the same position on SDS/PAGE but which can be resolved by 8 M urea/PAGE. RI-A and RI-B are both monomeric, but the molecular mass of RI-B (70-80 kDa) is significantly increased due to post-translational modification with lipopolysaccharide. All forms show absolute specificity for peptide bonds with Arg in the P1 position and are also capable of hydrolysing N-terminal Arg and C-terminal Arg-Arg peptide bonds. Thus they show limited amino- and carboxy-peptidase activity. For the hydrolysis of Nalpha-benzoyl-L-Arg-p-nitroanilide, the pH optimum is 8.0 at 30 degrees C. The Vmax for all three enzymes is controlled by ionization of two residues with apparent pKas at 30 degrees C of 6. 5+/-0.05 and 9.7+/-0.05, and DeltaH values of approximately 29 kJ/mol and approximately 24 kJ/mol in the enzyme-substrate complex. By analogy with papain, the pKa of 6.5 could be ascribed to a Cys and the pKa of 9.7 to a His residue. E-64 [L-trans-epoxysuccinyl-leucylamide-4-(4-guanidino)butane] is a competitive inhibitor of RI, RI-A and RI-B. Based on physical properties and kinetic behaviour, RI-A appears to be analogous to gingipain from P. gingivalis HG66. However the alpha/beta structure of RI differs significantly from that of the high-molecular-mass multimeric complex of gingipain containing four haemagglutinins described by others. Since the genes for RI and high-molecular-mass gingipain are identical, the data indicate that an alternative processing pathway is involved in the formation of RI from the initial precursor. Furthermore, the identical N-termini and enzymic properties of the catalytic component of RI, RI-A and RI-B suggest that the maturation pathway of the RI precursor may also give rise to RI-A and RI-B. The physiological functions of these isoforms and their role in the disease process may become more apparent through examination of their interactions with host proteins.
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PMID:Biochemical characterization of the arginine-specific proteases of Porphyromonas gingivalis W50 suggests a common precursor. 916 3

By measurement of serotonin levels, the translocation of platelets to various tissues was examined following intravenous injection of a lipopolysaccharide (LPS) into C3H/HeN mice. There was a rapid platelet accumulation (within 5 min and particularly in the lung), followed by a slower accumulation in the liver, which reached its plateau 3-5 h later. The severity of the anaphylactoid shock corresponded well with the magnitude of the rapid response. LPSs from the oral black-pigmented bacteria, Porphyromonas gingivalis and Prevotella intermedia, were much more potent in inducing the rapid platelet response than were those from the Enterobacteriaceae Escherichia coli and Salmonella typhimurium. However, LPSs from these Enterobacteriaceae were significantly more potent than those from black-pigmented bacteria in inducing the slow platelet response. There was also a contrast between their abilities to induce histidine decarboxylase, which forms histamine from histidine: LPSs from the Enterobacteriaceae were much more potent than those from black-pigmented bacteria.
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PMID:Contrasting effects of lipopolysaccharides (endotoxins) from oral black-pigmented bacteria and Enterobacteriaceae on platelets, a major source of serotonin, and on histamine-forming enzyme in mice. 918 Jan 80

Since prostaglandins (PGs) and histamine (HA) seem to be involved in the activation of the hypothalamic-pituitary-adrenal axis following immunochallenges with lipopolysaccharide (LPS) endotoxin and cytokines, we investigated whether the histaminergic and eicosanoid systems in the male rat brain interact in their regulation of ACTH secretion. The PG synthesis inhibitor indomethacin (10 mg/kg i.p.) attenuated the ACTH response to LPS (10 micrograms/kg i.p.) and HA (30 micrograms i.c.v.). Infusion of PGE1, PGE2 or PGF2 alpha (1 and/or 5 micrograms infused intracerebroventricularly) stimulated ACTH secretion. The ACTH response to PGE1 was inhibited by the HA synthesis inhibitor alpha-fluoromethyl-histidine and the H1 receptor antagonist mepyramine (MEP) but not the H2 receptor antagonist cimetidine (CIM). Neither MEP nor CIM affected the ACTH response to PGE2. MEP and CIM attenuated the ACTH response induced by PGF2 alpha. The findings indicate that HA and some PGs in the brain interact in their stimulatory regulation of ACTH secretion. Such an interaction may also be involved in their mediation of the ACTH response to immunochallenges.
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PMID:Histamine and prostaglandin interaction in the central regulation of ACTH secretion. 926 3


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