Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies indicate that viruses may influence polyphosphoinositide levels. This study has examined the effects of vaccinia virus infection on phospholipase C activity. Infection of BS-C-1 cells, an African Green Monkey kidney cell line, or A431 cells, a human carcinoma cell line, with vaccinia virus inhibits receptor-mediated phospholipase C activation. As a consequence, agonist-mediated Ca2+ mobilization in BS-C-1 cells also was inhibited by vaccinia virus infection. Alleviation of the inhibition of phospholipase C activation was observed in vaccinia virus-infected cells treated with cycloheximide without influencing uninfected cells. Treatment of infected cells with alpha-amanitin, an inhibitor of host mRNA synthesis but not virus mRNA synthesis, failed to alleviate the inhibition of phospholipase C activation. Together these results suggest that a virus-encoded gene product mediates the inhibition of phospholipase C activation without the need of a virus-induced host factor. Analysis of the processes involved in the formation of inositol (1,4,5)-trisphosphate and mobilization of intracellular Ca2+ indicate that the vaccinia virus gene product exerts its inhibitory effects at the level of phospholipase C activity. This may occur by either directly reducing the amount of phospholipase C, reducing the specific activity of phospholipase C, or by inhibiting the association of phospholipase C with its substrate, phosphatidylinositol 4,5-bisphosphate.
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PMID:Inhibition of agonist-induced activation of phospholipase C following poxvirus infection. 146 12

Chronic colonization with Staphylococcus aureus is found in 40-50% of the sputum producing patients with cystic fibrosis treated at Stockholm's Cystic Fibrosis Center, Huddinge University Hospital. 30-40% of these patients had increased ELISA IgG antibody titres against teichoic acid and against alpha-toxin. About half of the number of patients showed increased antibody titres to either antigen during infection. Increased antibody titres against staphylococcal antigens were only found in less than or equal to 10% of patients not chronically colonized with S. aureus (no different from the normal population). The serum titres of antistaphylococcal antibodies were significantly higher in the chronically colonized patients (p less than 0.001). Patients who were also chronically harbouring Pseudomonas aeruginosa had the highest titres of both antibodies. The titres increased with clinical signs of infection and were normalized by antimicrobial chemotherapy. To conclude, the use of ELISA IgG antibodies may prove suitable for routine evaluation of the need for, and control of the efficacy of antistaphylococcal chemotherapy in cystic fibrosis.
Infection
PMID:Antistaphylococcal antibodies in cystic fibrosis. 236 69

Infection of cultured endothelial cells with Trypanosoma cruzi alters intracellular Ca2+ homeostasis. To help understand the biochemical basis for this phenomenon, we determined the influence of infection on inositol phosphate formation in a broken cell preparation. Inositol phosphates participate in the regulation of cytosolic Ca2+. In uninfected endothelial cells, bradykinin guanosine 5'-O-thiophosphate (GTP tau S), and calcium all stimulated inositol phosphate (IP1), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) formation within 5 sec of incubation. At longer periods of incubation with GTP tau S and bradykinin, formation of IP1 was linear for 30 sec, whereas the rate of IP2 and IP3 generation was maximal at 20 and 5 sec, respectively. Second, infection markedly changed these aspects of inositol phosphate generation. First, unstimulated (basal) levels of IP1 and IP3 were markedly increased over those levels in membranes of uninfected cells. Infection decreased the rate of formation for the three inositol phosphates in response to GTP tau S and bradykinin. Finally, infection diminished the magnitude of inositol phosphate synthesis in response to Ca2+ for IP1, IP2, and IP3, respectively. Studies on G proteins using cholera and pertussis toxin were carried out to determine if the infection-associated changes in inositol phosphate generation could be attributed to functional changes in these regulatory proteins known to participate in the activation of phospholipase C. Infection markedly decreased the magnitude of cholera and pertussis toxin-dependent ADP ribosylation, as compared to control uninfected cells. Incubation of uninfected endothelial cells with cholera and pertussis toxin also decreased the magnitude of cholera and pertussis toxin ADP ribosylation. Despite the similar effects of infection and toxin treatment on subsequent toxin-catalyzed ADP ribosylation, toxin treatment did not influence inositol phosphate generation. Collectively, these results demonstrate an influence of infection on receptor-dependent and -independent synthesis of inositol phosphates, possibly by an action on phospholipase C. The results help to explain the apparent infection-associated increase in basal Ca2+ previously observed and suggest that interference with signal transduction may be a consequence of the presence of the parasite.
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PMID:Trypanosoma cruzi: infection of cultured human endothelial cells alters inositol phosphate synthesis. 250 35

Pseudomonas aeruginosa is a gram-negative pathogen, versatile and opportunistic in terms of its genetics, metabolic potential, and mechanisms of virulence. This versatility enables it to respond to variable and frequently adverse environmental conditions. Considered by many to be an aerobic organism, it is capable of growing anaerobically if certain substrates are available, for example, nitrates or arginine. Diversity of mechanisms of genetic exchange, including transformation, transduction, and conjugation, help P. aeruginosa adapt to changing conditions by acquiring new genetic information. Genetic manipulations have been exploited in recent years to study the basic biology of this bacterial species and the roles of its numerous virulence factors. Recently, transposon mutagenesis techniques and recombinant DNA methods (cloning) have been used to study some of the virulence factors of P. aeruginosa. The pathogenesis of P. aeruginosa infections is multifactorial, as manifested by the numerous toxins, or virulence factors, it produces and the variety of diseases it causes. P. aeruginosa is invasive and toxigenic. Infections appear to occur in stages: bacterial adherence, colonization, invasion and dissemination, and systemic or toxemic disease. Virulence factors can contribute to one or several stages of pathogenesis. Surface factors, including pili, lipopolysaccharide, and polysaccharide slime (alginate), probably contribute to the first two stages. Polysaccharide slime and lipopolysaccharide may also contribute to other processes later in the course of infection. Toxins, including exotoxin A and phospholipase C (hemolysin), and proteases of P. aeruginosa may contribute to tissue damage and dissemination. They may also aid in the procurement of nutrients required by the bacteria in the early stages of infection. The significance of the different virulence factors probably depends on the infection. Alginate production and phospholipase C are likely to have special significance in respiratory infections, particularly in cystic fibrosis.
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PMID:Pseudomonas aeruginosa: biology, mechanisms of virulence, epidemiology. 300 72

The effect of bacterial exotoxins and endotoxins on phagocytosis was tested on human macrophages in monolayer cultures by determining the rate of zymosan particle ingestion at different toxin concentrations and incubation times. The exotoxins tested were staphylococcal alpha-toxin and diphtheria-toxin. The endotoxins used were lipopolysaccharides from Salmonella typhi, Salmonella typhimurium, Shigella flexneri and Serratia marcescens. Phagocytosis was significantly impaired after prolonged incubation with diphtheria toxin whereas alpha-toxin was ineffective. Endotoxin-treated macrophages showed a wide range of phagocytic activity. Enhancement of phagocytosis was observed with a low concentration of endotoxin (1 microgram/ml) from S. typhi, S. typhimurium and S. flexneri. Higher concentrations (2.5 and 5 micrograms/ml) depressed phagocytosis to varying extents, except for S. typhi lipopolysaccharide, which did not induce a significant decrease in phagocytosis in comparison to the controls.
Infection
PMID:The influence of bacterial exotoxins and endotoxins on the phagocytic activity of human macrophages in culture. 635 Jan 91

An enzyme-linked immunosorbent assay (ELISA) was used with purified alpha-toxin and teichoic acid preparations to measure the IgG and IgM response in Staphylococcus aureus infections. After determining antibodies in a normal population, cut-off levels were set for all age groups. ELISA with alpha-toxin was more sensitive than the antistaphylolysin neutralization test (ASTA). Determining IgM antibodies with the two antigens was found to be of limited diagnostic value. Positive IgG titers against alpha-toxin were found in 21 of 27 patients (78%) with endocarditis, 11 of 14 (79%) with complicated septicemia, eight of 20 (40%) with uncomplicated septicemia and in 12 of 22 (54%) with chronic osteomyelitis. The IgG responses to teichoic acid and alpha-toxin were somewhat different when measured by ELISA, and the parallel performance of the two assays resulted in improved serological diagnostics. The number of positive patients increased to 89%, 86%, 65% and 64%, respectively, in the four groups with a diagnostic specificity of 93%. In septicemic staphylococcal infections, the diagnosis could be established in all patients (28 of 28) with adequately spaced paired samples.
Infection
PMID:The role of antibodies against alpha-toxin and teichoic acid in the diagnosis of staphylococcal infections. 686 37

Infection of human cells with poliovirus leads to modification of phospholipase activity. Phospholipase C, which generates inositol triphosphate, is stimulated, whereas the activation of phospholipase A2 by the calcium ionophore A23187 is inhibited. Analysis of phospholipid moieties in media of HeLa cells infected with poliovirus indicates that the release of fatty acids is not enhanced during infection, suggesting that phospholipase A1 and A2 activities are not stimulated. The release of choline into the medium is significantly higher 3 h after infection, indicating that a phospholipase that has phosphatidylcholine as its substrate becomes activated. This activation requires viral gene expression because inhibitors of poliovirus gene expression added at the beginning of infection block choline release, but continuous viral protein synthesis is not required. Choline and phosphorylcholine are released into the medium, but the pools of both are gradually depleted in poliovirus-infected cells, perhaps as a consequence of their release into the medium and the increased synthesis of phospholipids that takes place in poliovirus-infected cells. Inhibitors of phospholipase activity such as mepacrine, zinc or cadmium ions significantly reduce this increased release of choline from poliovirus-infected cells. Labelling of cells with [3H]phosphatidylcholine suggests that the choline released from infected cells comes, at least in part, from the hydrolysis of this compound. These results indicate that, in addition to the activation of the phospholipase C which hydrolyses phosphatidylinositol in poliovirus-infected cells, a phospholipase C that acts on a phosphatidylcholine is also activated.
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PMID:Enhancement of phospholipase activity during poliovirus infection. 838 98

Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. We recently reported that L. monocytogenes induces up-regulation of E-selectin and other endothelial adhesion molecules and subsequent polymorphonuclear leukocyte (PMN) adhesion into cultured human endothelial cells. In the present study, we characterized the mechanisms of enhanced E-selectin expression using L. monocytogenes wild type (EGD), the isogenic in-frame deletion mutants for phosphatidylcholine (PC)- and phosphatidylinositol (PI)-specific phospholipases EGD delta plcA and EGD delta plcB, as well as the nonvirulent control strain Listeria innocua. Infection of endothelial cells with EGD delta plcA or EGD delta plcB for 6 h induced, as compared with EGD wild type, intermediate levels of E-selectin mRNA and protein as well as PMN rolling and adhesion at a shear rate of 1 dyne/cm2, indicating that both bacterial phospholipases are required for a maximal effect. Similarly, ceramide content and NF-kappa B activity were increased in L. monocytogenes-exposed endothelial cells, but only to intermediate levels for PC- or PI-phospholipase C (PLC)-deficient listerial mutants. Phospholipase effects could be mimicked by exogenously added ceramides or bacterial sphingomyelinase. The data presented indicate that PI-PLC and PC-PLC are important virulence factors for L. monocytogenes infections that induce accumulation of ceramides that in turn may act as second messengers to control host cell signal-transduction pathways leading to persistent NF-kappa B activation, increased E-selectin expression, and enhanced PMN rolling/adhesion. The ability of L. monocytogenes to stimulate PMN adhesion to endothelial cells may be an important mechanism in the pathogenesis of severe listeriosis.
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PMID:Two distinct phospholipases C of Listeria monocytogenes induce ceramide generation, nuclear factor-kappa B activation, and E-selectin expression in human endothelial cells. 974 65

The first reported case of Clostridium septicum myonecrosis in an adult with aplastic anemia is described. The patient presented with sepsis, a parapharyngeal abscess that necessitated emergent intubation, and severe intravascular hemolysis attributed to clostridial alpha-toxin production. Despite prompt recognition and treatment, the patient died of his infection. C. septicum myonecrosis should be considered in any immunocompromised patient with sepsis, especially when accompanied by evidence of multiple sites of tissue infection.
Infection
PMID:Clostridium septicum myonecrosis presenting as a parapharyngeal abscess in a patient with aplastic anemia. 979 92

Semliki Forest virus (SFV) vectors have been efficiently used for rapid high level expression of several G protein-coupled receptors. Here we describe the use of SFV vectors to express the alpha 1b-adrenergic receptor (AR) alone or in the presence of the G protein alpha q and/or beta 2 and gamma 2 subunits. Infection of baby hamster kidney (BHK) cells with recombinant SFV-alpha 1b-AR particles resulted in high specific binding activity of the alpha 1b-AR (24 pmol receptor/mg protein). Time-course studies indicated that the highest level of receptor expression was obtained 30 hours post-infection. The stimulation of BHK cells, with epinephrine led to a 5-fold increase in inositol phosphate (IP) accumulation, confirming the functional coupling of the receptor to G protein-mediated activation of phospholipase C. The SFV expression system represents a rapid and reproducible system to study the pharmacological properties and interactions of G protein coupled receptors and of G protein subunits.
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PMID:Expression of the alpha 1b-adrenergic receptor and G protein subunits in mammalian cell lines using the Semliki Forest virus expression system. 1007 71


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