UNIPROT:P43026 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We demonstrated recently that the production of tumor necrosis factor (TNF) is induced in normal mice and in the immunosuppressed nude mouse model by the administration of muramyl dipeptide (MDP) derivatives followed by endotoxin (lipopolysaccharide). In the present study, the ability of this treatment to induce the production of TNF in mice receiving cyclophosphamide (CY) was examined. Two days following treatment with high-dose CY (250 mg/kg), mice exhibited leukocytopenia and drastically reduced splenic weight. However, these animals remained capable of producing TNF, albeit at lower levels, when treated with MDP derivatives and lipopolysaccharide (LPS), particularly when the lipophilic analogue MDP-dipalmitoyl glycerol (GDP) was utilized. TNF was also induced by the administration of MDP-GDP and LPS to Meth A sarcoma-bearing mice treated with this dose of CY. Furthermore, in all animals receiving this combination therapy, sarcoma necrosis and complete regression were obtained without any sign of tumor regrowth. A dose of 100 mg/kg CY was not effective for inhibiting tumor regrowth under the same experimental conditions. These results demonstrated that the anti-tumor activity of endogenously induced TNF is potentiated by combined therapy with a high dose of CY.
...
PMID:Production and enhanced anti-tumor activity of tumor necrosis factor in mice treated with cyclophosphamide. 212 96

Gram-negative vaccines can elicit the production of tumor necrosis factor (TNF) in mice primed by muramyl dipeptide (MDP) or by its lipophilic derivative MDP-dipalmitoyl glycerol (MDP-GDP). In mice pretreated with MDP and particularly with MDP-GDP, Bordetella pertussis vaccine was shown to be more effective than typhoid vaccine. The time course of TNF production in the blood did not indicate any difference between the effect of MDP or of MDP-GDP. In both cases the cytotoxic activity reached maximal levels by 2 h after injection of the bacterial preparations and returned to normal values between 3 and 5 h after the challenge. In nude mice, high titers of circulating TNF were also produced by combined treatment with MDP-GDP and bacterial vaccine. Moreover, in tumor-bearing mice the association of MDP or of MDP-GDP to a bacterial vaccine induced a strong hemorrhagic necrosis, whereas each treatment alone was inactive. It was also found that mice were less sick when they were primed with MDP-GDP than with MDP, and when TNF was elicited by B. pertussis instead of lipopolysaccharide. Moreover, nude mice appeared more resistant to shock and to hemoconcentration than normal mice.
...
PMID:Production of tumor necrosis factor in nude mice by muramyl peptides associated with bacterial vaccines. 316 34

The membrane fraction from a mutant of Salmonella anatum deficient in UDPgalactose-4-epimerase, utilized synthetic ficaprenyl alpha-D-galactosyl diphosphate as a substrate in the biosynthesis of the O-polysaccharide portion of lipopolysaccharide which has a mannosylrhamnosylgalactose repeating sequence. The galactosyl lipid was prepared by chemical synthesis from D-galactose and ficaprenol extracted from Ficus elastica. Membrane preparations catalyzed the transfer of rhamnose from TDP-rhamnose onto membrane-bound ficaprenyl galactosyl diphosphate forming rhamnosylgalactosyl ficaprenyl diphosphate; the reaction was dependent on the prior insertion of the synthetic glycosyl-lipid into the membrane, and was proportional to incubation time up to 4 min at 29 degrees C. When both TDP-rhamnose and GDP-mannose were added, the product formed was O-polysaccharide. These results indicate that the chemically synthesized ficaprenyl galactosyl diphosphate can be an active substrate for the in vitro synthesis of the Salmonella O-polysaccharide.
...
PMID:Chemically synthesized galactosyl ficaprenyl diphosphate as an intermediate in the biosynthesis of the Salmonella O-antigenic polysaccharide. 618 14

The rfbO9 gene cluster, which is responsible for the synthesis of the lipopolysaccharide O9 antigen, was cloned from Escherichia coli O9:K30. The gnd gene, encoding 6-phosphogluconate dehydrogenase, was identified adjacent to the rfbO9 cluster, and by DNA sequence analysis the gene order gnd-rfbM-rfbK was established. This order differs from that described for other members of the family Enterobacteriaceae. Nucleotide sequence analysis was used to identify the rfbK and rfbM genes, encoding phosphomannomutase and GDP-mannose pyrophosphorylase, respectively. In members of the family Enterobacteriaceae, these enzymes act sequentially to form GDP-mannose, which serves as the activated sugar nucleotide precursor for mannose residues in cell surface polysaccharides. In the E. coli O9:K30 strain, a duplicated rfbM2-rfbK2 region was detected approximately 3 kbp downstream of rfbM1-rfbK1 and adjacent to the remaining genes of the rfbO9 cluster. The rfbM isogenes differed in upstream flanking DNA but were otherwise highly conserved. In contrast, the rfbK isogenes differed in downstream flanking DNA and in 3'-terminal regions, resulting in slight differences in the sizes of the predicted RfbK proteins. RfbMO9 and RfbKO9 are most closely related to CpsB and CpsG, respectively. These are isozymes of GDP-mannose pyrophosphorylase and phosphomannomutase, respectively, which are thought to be involved in the biosynthesis of the slime polysaccharide colanic acid in E. coli K-12 and Salmonella enterica serovar Typhimurium. An E. coli O-:K30 mutant, strain CWG44, lacks rfbM2-rfbK2 and has adjacent essential rfbO9 sequences deleted. The remaining chromosomal genes are therefore sufficient for GDP-mannose formation and K30 capsular polysaccharide synthesis. A mutant of E. coli CWG44, strain CWG152, was found to lack GDP-mannose pyrophosphorylase and lost the ability to synthesize K30 capsular polysaccharide. Wild-type capsular polysaccharide could be restored in CWG152, by transformation with plasmids containing either rfbM1 or rfbM2. Introduction of a complete rfbO9 gene cluster into CWG152 restored synthesis of both O9 and K30 polysaccharides. Consequently, rfbM is sufficient for the biosynthesis of GDP-mannose for both O antigen and capsular polysaccharide E. coli O9:K30. Analysis of a collection of serotype O8 and O9 isolates by Southern hybridization and PCR amplification experiments demonstrated extensive polymorphism in the rfbM-rfbK region.
...
PMID:Cloning and analysis of duplicated rfbM and rfbK genes involved in the formation of GDP-mannose in Escherichia coli O9:K30 and participation of rfb genes in the synthesis of the group I K30 capsular polysaccharide. 751 42

The O-repeating unit of the Escherichia coli O7-specific lipopolysaccharide is made of galactose, mannose, rhamnose, 4-acetamido-4,6-dideoxyglucose, and N-acetyglucosamine. We have recently characterized the genes involved in the biosynthesis of the sugar precursor GDP-mannose occurring in the E. coli O7:K1 strain VW187 (C. L. Marolda and M. A. Valvano, J. Bacteriol. 175:148-158, 1993). In the present study, we identified and sequenced the rfbBDAC genes encoding the enzymes for the biosynthesis of another precursor, dTDP-rhamnose. These genes are localized on the upstream end of the rfbEcO7 region, and they are strongly conserved compared with similar genes found in various enteric and nonenteric bacteria. Upstream of rfbB we identified a DNA segment containing the rfb promoter and a highly conserved untranslated leader sequence also present in the promoter regions of other surface polysaccharide gene clusters. Also, we have determined that rfbB and rfbA have homologs, rffG (o355) and rffH (o292), respectively, located on the rff cluster, which is involved in the synthesis of enterobacterial common antigen. We provide biochemical evidence that rffG and rffH encode dTDP-glucose dehydratase and glucose-1-phosphate thymidylyltransferase activities, respectively, and we also show that rffG complemented the rfbB defect in the O7+ cosmid pJHCV32. We also demonstrate that rffG is distinct from rffE and map the rffE gene to the second gene of the rff cluster.
...
PMID:Genetic analysis of the dTDP-rhamnose biosynthesis region of the Escherichia coli VW187 (O7:K1) rfb gene cluster: identification of functional homologs of rfbB and rfbA in the rff cluster and correct location of the rffE gene. 755 40

The O7-specific lipopolysaccharide (LPS) in strains of Escherichia coli consists of a repeating unit made of galactose, mannose, rhamnose, 4-acetamido-2,6-dideoxyglucose, and N-acetylglucosamine. We have recently cloned and characterized genetically the O7-specific LPS biosynthesis region (rfbEcO7) of the E. coli O7:K1 strain VW187 (C. L. Marolda, J. Welsh, L. Dafoe, and M. A. Valvano, J. Bacteriol. 172:3590-3599, 1990). In this study, we localized the gnd gene encoding gluconate-6-phosphate dehydrogenase at one end of the rfbEcO7 gene cluster and sequenced that end of the cluster. Three open reading frames (ORF) encoding polypeptides of 275, 464, and 453 amino acids were identified upstream of gndEcO7, all transcribed toward the gnd gene. ORF275 had 45% similarity at the protein level with ORF16.5, which occupies a similar position in the Salmonella enterica LT2 rfb region, and presumably encodes a nucleotide sugar transferase. The polypeptides encoded by ORFs 464 and 453 were expressed under the control of the ptac promoter and visualized in Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gels and by maxicell analysis. ORF464 expressed GDP-mannose pyrophosphorylase and ORF453 encoded a phosphomannomutase, the enzymes for the biosynthesis pathway of GDP-mannose, one of the nucleotide sugar precursors for the formation of the O7 repeating unit. They were designated rfbMEcO7 and rfbKEcO7, respectively. The RfbMEcO7 polypeptide was homologous to the corresponding protein in S. enterica LT2, XanB of Xanthomonas campestris, and AlgA of Pseudomonas aeruginosa, all GDP-mannose pyrophosphorylases. RfbKEcO7 was very similar to CpsG of S. enterica LT2, an enzyme presumably involved in the biosynthesis of the capsular polysaccharide colanic acid, but quite different from the corresponding RfbK protein of S. enterica LT2.
...
PMID:Identification, expression, and DNA sequence of the GDP-mannose biosynthesis genes encoded by the O7 rfb gene cluster of strain VW187 (Escherichia coli O7:K1). 767 91

1. Purinoceptor agonist-induced currents in untreated (proliferating) and lipopolysaccharide- (LPS; 100 ng ml-1) treated (non-proliferating) rat microglial cells were recorded by the whole-cell patch-clamp technique. 2. In non-proliferating microglia, adenosine (0.01-100 microM), 2-methylthio ATP (3-3000 nM), ATP (0.1-1000 microM), and ATP-gamma-S (1-10 microM), but not alpha,beta-methylene ATP (alpha,beta-MeATP; 100 microM) produced a slow outward current at a holding potential of 0 mV. When K+ was replaced in the pipette solution by an equimolar concentration of Cs+ (150 mM), the 2-methylthio ATP- (300 nM) induced outward current disappeared. The effect of 2-methylthio ATP (300 nM) did not depend on the presence of extracellular Mg2+ (1 mM). The outward current response to 2-methylthio ATP (300 nM) was larger in proliferating than in non-proliferating microglia. 3. ATP (1-1000 microM) evoked a fast inward current at a holding potential of -70 mV in nonproliferating microglia, while adenosine (100-1000 microM) was inactive. When the effects of ATP were compared at 0 and -70 mV, it became evident that ATP is much more potent in evoking the outward current. 4. The 2-methylthio ATP- (300 nM) induced outward current was blocked by suramin (300 microM), but not by 8-(p-sulphophenyl)-theophylline (100 microM), while the adenosine- (1 microM) induced outward current had the reverse sensitivity to these antagonists. 5. The 2-methylthio ATP- (300 nM) induced outward current was inhibited by inclusion of GDP-beta-S(200 microM) into the pipette solution or by preincubation of microglial cells with pertussis toxin(50 ng ml-1) for 12 h. The 2-methylthio ATP- (300 microM) induced inward current was not changed by intracellular GDP-beta-S (200 microM). The outward current response to adenosine (1 microM) was also abolished after pretreatment with pertussis toxin (50 ng ml-1).6. Rat microglia possess both ATP-sensitive P2y- and adenosine-sensitive P1-purinoceptors. The ATP evoked inward current is mediated by P2y-purinoceptors, while the ATP- and adenosine-evoked outward currents are mediated by P2y- and P1-purinoceptors, respectively. The transduction mechanisms of the outward, but not the inward current activation involve a pertussis toxin-sensitive G protein.
...
PMID:Characterization and transduction mechanisms of purinoceptors in activated rat microglia. 781 23

Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.
...
PMID:Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. 813 77

The first four genes (rfbA,B,D,E) of the rfb region of Vibrio cholerae O1 are predicted to encode the enzymes required for the biosynthesis of perosamine, which constitutes the backbone structure of the O-antigen of the lipopolysaccharide. Based on homology to known proteins/protein families, the following functions are predicted: RfbA, phosphomannose isomerase-guanosine diphosphomannose pyrophosphorylase; RfbB, phosphomanno-mutase; RfbD, oxido reductase and RfbE, perosamine synthetase (amino-transferase). Thus, perosamine is synthesized from fructose 6-phosphate via the intermediates mannose 6-phosphate by RfbA, to mannose 1-phosphate by RfbB, to GDP-mannose by RfbA, to GDP-4-keto-6-dideoxymannose by RfbD and to GDP-perosamine by RfbE. This final product would then serve as the substrate for the addition of the tetronate, which could then be polymerized into the O-antigen for transfer to the lipid A plus core oligosaccharide and export to the cell surface. The organization of these genes are such that one would expect them to be translationally coupled as part of the rfb operon. However, the absence of readily detectable promoter sequences suggests low levels of transcription, in line with other studies. The nucleotide sequence of these genes is absolutely conserved in the two isolates 569B (classical, Inaba) and O17 (El Tor, Ogawa) which were expected to show maximal sequence variation. This suggests very tight constraints on the micro-evolution within these sequences.
...
PMID:A putative pathway for perosamine biosynthesis is the first function encoded within the rfb region of Vibrio cholerae O1. 852 91

The lipopolysaccharide of Rhizobium leguminosarum differs from that of other Gram-negative organisms. R. leguminosarum lipid A lacks phosphate groups, but it contains a galacturonic acid residue at the 4'-position and an aminogluconate moiety in place of the usual glucosamine 1-phosphate unit. R. leguminosarum lipid A is esterified with a peculiar long chain fatty acid, 27-hydroxyoctacosanoate, not found in enteric Gram-negative bacteria, and the inner core of R. leguminosarum contains mannose and galactose in place of heptose. Despite these differences, the biosynthesis of R. leguminosarum lipid A is initiated by the same seven enzyme pathway as in Escherichia coli (Raetz, C. R. H. (1993) J. Bacteriol. 175, 5745-5753) to form the phosphorylated precursor, (Kdo)2-lipid IVA, which is then processed differently. We now describe several novel Rhizobium-specific enzymes that recognize and modify (Kdo)2-lipid IVA. The 1- and 4'-phosphatases were detected using (Kdo)2-[1-32P]-lipid IVA and (Kdo)2-[4'-32P]-lipid IVA, respectively, as shown by release of 32Pi. In the presence of GDP-mannose and/or UDP-galactose, membranes of R. leguminosarum first transferred mannose and then galactose to (Kdo)2-[4'-32P]-lipid IVA. In addition, at least two hydrophobic metabolites were generated from (Kdo)2-[4'-32P]-lipid IVA in a manner that was dependent upon both membranes and a cytosolic factor from R. leguminosarum. These compounds are attributed to novel acylations of (Kdo)2-[4'-32P]-lipid IVA. E. coli membranes and cytosol did not catalyze any of the unique reactions detected in R. leguminosarum extracts. Our findings establish the conservation and versatility of (Kdo)2-lipid IVA as a lipid A precursor in bacteria.
...
PMID:Lipopolysaccharide biosynthesis in Rhizobium leguminosarum. Novel enzymes that process precursors containing 3-deoxy-D-manno-octulosonic acid. 894 64

1 2 3 4 5 6 Next >>