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

1. The defective Cl- secretion characteristic of cystic fibrosis airway epithelial cells can be bypassed by an alternative Ca2+ dependent Cl- secretory pathway that is activated by extracellular nucleotides, e.g. uridine-5'triphosphate (UTP), acting on P2U purinoceptors. Since UTP is susceptible to hydrolysis by nucleotidases and phosphatases present in the airways, the identification of stable P2U-purinoceptor agonists would be of therapeutic relevance. 2. Uridine-5'-O-(3-thiotriphosphate) (UTP gamma S) was synthesized by nucleoside diphosphate kinase-catalyzed transfer of the gamma-phosphorothioate from guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) or adenosine-5' = O-(3-thiotriphosphate) (ATP gamma S) to UDP. Formation of UTP gamma S was illustrated by observation of transfer of 35S from [35S]-GTP gamma S and transfer of 3H from [3H]-UDP. The chemical identity of high performance liquid chromatography (h.p.l.c.)-purified UTP gamma S was confirmed by nuclear magnetic resonance analysis. 3. Human 1321N1 astrocytoma cells stably expressing the phospholipase C-coupled human P2U-purinoceptor were utilized to test the activity of UTP gamma S. UTP gamma S (EC50 = 240 nM) was essentially equipotent to UTP and ATP for stimulation of inositol phosphate formation. 4. Unlike [3H]-UTP, [3H]-UTP gamma S was not hydrolyzed by alkaline phosphatase, acid phosphatase, or apyrase. Moreover, no hydrolysis was detected during a 1 h incubation with human nasal epithelial cells. 5. UTP gamma S was equally potent and efficacious with UTP for stimulation of Cl- secretion by human nasal epithelium from both normal donors and cystic fibrosis patients. Based on its high potency and resistance to hydrolysis, UTP gamma S represents a promising compound for treatment of cystic fibrosis.
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PMID:Enzymatic synthesis of UTP gamma S, a potent hydrolysis resistant agonist of P2U-purinoceptors. 882 64

The cells of Burkholderia pseudomallei, B. cepacia and Pseudomonas aeruginosa grown on agar plates were stained with fluorescently-labeled insulin. The former two species were stained positively indicating insulin binding but P. aeruginosa was not. Insulin exposure reduced phospholipase C and acid phosphatase activities of B. pseudomallei but did not affect those enzymatic activities of B. cepacia in the employed experimental conditions. It is suggested that B. pseudomallei have insulin receptors which may be associated with a signal transfer system involving phospholipase and protein tyrosine phosphatase.
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PMID:Affinity and response of Burkholderia pseudomallei and Burkholderia cepacia to insulin. 918 75

In Kluyveromyces lactis, the cell wall compositions of Kl (ATCC 96897), a wild sensitive strain, and Klm (ATCC 96896), a strain resistant to amphotericin B (AmB), were shown to be very different, since the walls in the latter were significantly enriched in hexosamine, but had a reduced content in phosphate and amino acid. In both strains, the cell walls limited their sensitivity to this antifungal agent. The absence of cell wall increased the sensitivity of the cells to this polyene by 5 to 10-fold. When the cells were treated with enzymes such as pronase and chitinase in order to change the cell wall structure just before inoculation, the yeasts appeared more resistant to the antibiotic. However, treatments with chymopapain and phospholipase C did not significantly change the sensitivity of the two strains to this agent. Cells treated with acid phosphatase displayed a longer lag phase than the control cells. In addition, when cultured in the presence of AmB, the cells were less sensitive to this agent. The present results reveal that both a change in the ionic charges of the cell wall and an alteration in the cell wall structure modified the sensitivity of these yeast strains to AmB.
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PMID:Implication of cell wall constituents in the sensitivity of Kluyveromyces lactis strains to amphotericin B. 976 14

An acid phosphatase (AP) and a phosphorylcholine hydrolase (PCH) were detected in excretory-secretory (ESP) products from adult Haemonchus contortus. The AP had a pH optimum of 4.5 and was inhibited by tartaric acid and sodium fluoride, but not by o-phenanthroline. The AP hydrolyzed paranitrophenol (pnp)-phosphate and to a lesser extent pnp-phenyl-phosphonate but did not hydrolyze diester substrates. Purified AP consisted of heterodimers with relative molecular weight (Mr) of 41.9 and 48.7 kDa and had a native molecular weight of 98 kDa by size-exclusion chromatography (SEC). The PCH had a pH optimum of about 9.5 and was inhibited by EDTA and o-phenanthroline but not by the specific phospholipase inhibitor D609. The specific activity of PCH in the ESP was approximately 25-fold less than that of AP. PCH also hydrolyzed 5'-thymidine monophosphate-pnp at a rate about 40% lower than pnp-phosphorylcholine but did not hydrolyze 3'-thymidine monophosphate-pnp. Partial purification of PCH suggests an Mr of 50.2 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 102 kDa by SEC. Both AP and PHC were secreted in vitro in a time-dependent manner and had their highest concentrations in the intestine. The results indicate that H. contortus adults secrete significant amounts of AP that might be a digestive enzyme. PCH is also an intestinal enzyme and is secreted in lesser amounts than AP. The PCH is probably not a phospholipase C but has some characteristics of a type I phosphodiesterase.
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PMID:Characterization of acid phosphatase and phosphorylcholine hydrolase in adult Haemonchus contortus. 1070 55

Peritoneal and bronchoalveolar macrophages activated in vitro by endotoxin, exhibit alterations in the acid phosphatase activity of cell lysates when certain hormones or autacoids are present in the culture medium. They also show morphological changes concerning general appearance and acid phosphatase cytochemistry. Certain agents known to increase the intracellular levels of cyclic AMP, such as dopamine and prostaglandin E2, decreased this enzyme activity in the lysates of peritoneal macrophages. Adrenalin had no effect on this activity at 14 hours, but was found to increase the activity in the culture medium at the initial hours of incubation. Glucagon decreased whereas insulin increased acid phosphatase activity in bronchoalveolar macrophages. Serotonin or histamine, known to activate phospholipase C, increased this activity in peritoneal or bronchoalveolar macrophages. The results of this study, taken together with previously published data (Kondomerkos et al., 2003), suggest that hormones and autacoids may control certain parameters of macrophage activation including acid phosphatase activity.
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PMID:In vitro effects of hormones and autacoids on the activity of acid phosphatase in the lysates of endotoxin-activated rat peritoneal and bronchoalveolar macrophages. 1297 79

We recently reported that cultivation of oat (Avena sativa L.) without phosphate resulted in plasma membrane phosphoglycerolipids being replaced to a large extent by digalactosyldiacylglycerol (DGDG) (Andersson, M. X., Stridh, M. H., Larsson, K. E., Liljenberg, C., and Sandelius, A. S. (2003) FEBS Lett. 537, 128-132). We report here that DGDG is not the only non-phosphorous-containing lipid that replaces phospholipids but that also the content of glucosylceramides and sterolglycosides increased in plasma membranes as a response to phosphate starvation. In addition, phosphate deficiency induced similar changes in lipid composition in the tonoplast. The phospholipid-to-glycolipid replacement apparently did not occur to any greater extent in endoplasmic reticulum, Golgi apparatus, or mitochondrial inner membranes. In contrast to the marked effects on lipid composition, the polypeptide patterns were largely similar between root plasma membranes from well-fertilized and phosphate-limited oat, although the latter condition induced at least four polypeptides, including a chaperone of the HSP80 or HSP90 family, a phosphate transporter, and a bacterial-type phosphoesterase. The latter polypeptide reacted with an antibody raised against a phosphate deficiency-induced phospholipase C from Arabidopsis thaliana (Nakamura, Y., Awai, K., Masuda, T., Yoshioka, Y., Takamiya, K., and Ohta, H. (2005) J. Biol. Chem. 280, 7469-7476). In plasma membranes from oat, however, a phospholipase D-type activity and a phosphatidic acid phosphatase were the dominant lipase activities induced by phosphate deficiency. Our results reflect a highly developed plasticity in the lipid composition of the plasma membrane and the tonoplast. In addition, phosphate deficiency-induced alterations in plasma membrane lipid composition may involve different sets of lipid-metabolizing enzymes in different plant tissues or species, at different stages of plant development and/or at different stages of stress adjustments.
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PMID:Phosphate-limited oat. The plasma membrane and the tonoplast as major targets for phospholipid-to-glycolipid replacement and stimulation of phospholipases in the plasma membrane. 1592 62

AcpA is a respiratory burst-inhibiting acid phosphatase from the Centers for Disease Control and Prevention Category A bioterrorism agent Francisella tularensis and prototype of a superfamily of acid phosphatases and phospholipases C. We report the 1.75-A resolution crystal structure of AcpA complexed with the inhibitor orthovanadate, which is the first structure of any F. tularensis protein and the first for any member of this superfamily. The core domain is a twisted 8-stranded beta-sheet flanked by three alpha-helices on either side, with the active site located above the carboxyl-terminal edge of the beta-sheet. This architecture is unique among acid phosphatases and resembles that of alkaline phosphatase. Unexpectedly, the active site features a serine nucleophile and metal ion with octahedral coordination. Structure-based sequence analysis of the AcpA superfamily predicts that the hydroxyl nucleophile and metal center are also present in AcpA-like phospholipases C. These results imply a phospholipase C catalytic mechanism that is radically different from that of zinc metallophospholipases.
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PMID:Structure of Francisella tularensis AcpA: prototype of a unique superfamily of acid phosphatases and phospholipases C. 1689 53

AcpA of Francisella spp. is a respiratory-burst-inhibiting acid phosphatase that also exhibits phospholipase C activity. To better understand the molecular basis of AcpA in virulence, a deletion of acpA was constructed in Francisella novicida. The phosphatase and lipase activities were reduced 10-fold and 8-fold, respectively, in the acpA mutant compared to the wild type and were found mostly associated with the outer membrane. The acpA mutant was more susceptible to intracellular killing than the wild-type strain in the THP-1 human macrophage-like cell line. In addition, mice infected with the acpA mutant survived longer than the wild-type strain and were less fit than the wild-type strain in competition infection assays. Transmission electron microscopy showed that the acpA mutant was delayed in escape from macrophage phagosomes, as more than 75% of acpA mutant bacteria could still be found inside phagosomes after 12 h of infection in THP-1 cells and human monocyte-derived macrophages, whereas most of the wild-type bacteria had escaped from the phagosome by 6 h postinfection. Thus, AcpA affects intracellular trafficking and the fate of Francisella within host macrophages.
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PMID:AcpA is a Francisella acid phosphatase that affects intramacrophage survival and virulence. 1706 Apr 65

Pseudomonas aeruginosa is a serious pathogen involved in nosocomial infections. Its pathogenicity is owed to rich production of virulence factors (VIFs) regulated by several complex hierarchical signal systems depending on environmental conditions, medium composition, and the presence of certain active compounds in it. Choline (Ch), which exists in patient tissues, and ethanol (Et), whose consumption aggravates infections, were reported to augment this microbe virulence. The goal of the present study was to show the effect of Et addition to P. aeruginosa cultures in two media (minimal culture medium [MM] and Eagon-Grelet medium [EGM]) in the absence or presence of Ch on its VIF levels. In MM, Et sharply repressed the basal and Ch-induced levels of the P. aeruginosa lectins PA-IL (galactose-specific) and PA-IIL (fucose/mannose-binding) and proteolytic activities, while increasing C(6)-HSL (autoinducer), hemolytic phospholipase C (PLC-H), and phosphatase levels. In EGM, it profoundly increased lectin, protease, pyocyanin, rhamnolipid (RhaL), autoinducer, and slightly phosphatase levels, but reduced Ch-induced protease, PLC-H, and acid phosphatase activities, except the short-chain HSL levels, which were increased by Et in combination with Ch. The presented results enlighten part of the complex molecular basis of Et-induced aggravation of P. aeruginosa infections due to increasing the bacterium virulence, which runs in parallel to suppression of the patient's immunity.
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PMID:Ethanol effects on Pseudomonas aeruginosa lectin, protease, hemolysin, pyocyanin, autoinducer, and phosphatase levels depending on medium composition and choline presence. 1730 40

Ras activation as a consequence of antigen receptor (T-cell receptor; TCR) engagement on T lymphocytes is required for T-cell development, selection and function. Lymphocyte function-associated antigen-1 (LFA-1) mediates lymphocyte adhesion, stabilization of the immune synapse and bidirectional signalling. Using a fluorescent biosensor we found that TCR activation with or without costimulation of CD28 led to activation of Ras only on the Golgi apparatus, whereas costimulation with LFA-1 induced Ras activation on both the Golgi and the plasma membrane. Ras activation on both compartments required RasGRP1, an exchange factor regulated by calcium and diacylglycerol (DAG), but phospholipase C (PLC) activity was required only for activation on the Golgi. Engagement of LFA-1 increased DAG levels at the plasma membrane by stimulating phospholipase D (PLD). PLD2 and phosphatidic acid phosphatase (PAP) were required for Ras activation on the plasma membrane. Thus, LFA-1 acts through PLD2 to reshape the pattern of Ras activation downstream of the TCR.
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PMID:The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2. 1748 17


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