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

A phospholipase C in bile, free of bacterial infection, has recently been identified from cholesterol gallstone patients. Because of the importance of phosphatidylcholine in solubilizing cholesterol in bile, this study further investigates the metabolism of phosphatidylcholine in delipidated gallbladder and common bile duct biles. Phospholipase C activity, as measured by the release of phosphoryl[3H]choline from the substrate 1,2-dipalmitoyl-sn-glycero-3-phospho [N-methyl-3H]choline, was identified in both hepatic and gallbladder biles. Similar levels of activity (nmol.h-1.mg-1 of delipidated protein) were found in common bile duct (11.25 +/- 14.23) and gallbladder bile (19.07 +/- 22.24), although per milliliter of bile, the mean gallbaldder levels were 6.4 times greater than those found in common duct bile. With the tow substrates, 1-palmitoyl-2[9,10-3H] palmitoyl-sn-glycero-3-phosphocholine and 1,2(1-14C) dipalmitoyl-sn-glycero-3-phosphocholine, the majority of organically extracted label, after thin-layer chromatography, was recovered as radiolabeled diglyceride, confirming the presence of phospholipase C. Diglyceride levels were found to be closely correlated with [3H]choline (slope, 0.9820; r = 0.9844). In addition to diglyceride, both radiolabeled free fatty acid and monoglyceride were identified in common bile duct and gallbladder biles, although their levels were an order of magnitude less than measurable phospholipase C activity. To determine whether the free fatty acid release was due to either a diacylglycerol-lipase or a phospholipase A2, the effect of adding unlabeled diglyceride on free fatty acid formation from the substrate [14C]DPPC was examined. As the concentration of unlabeled diglyceride was increased, the amount of free fatty acid and monoglyceride released were both reduced in parallel. Direct measurement of diacylglycerol-lipase activity by incubating the diglyceride, sn-2[3H]dipalmitoyl, resulted in release of both products in a ratio similar to that found with sn-2[3H]DPPC. Finally, no radiolabeled lysolecithin was identified with [3H]choline-DPPC or [14C]DPPC as substrate indicating the free fatty acid was the product of a diacylglycerol-lipase rather than a phospholipase A2. Phospholipase C and diacyl-glycerol-lipase activities were significantly correlated (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phospholipase C and diacylglycerol lipase in human gallbladder and hepatic bile. 206 34

Previous studies have demonstrated that a number of membrane-active agents are capable of binding to the surface of polymorphonuclear leukocytes (PMN) resulting in an augmentation of superoxide anion and hydrogen peroxide (H2O2) production in response to soluble stimuli. It is now demonstrated that these same membrane-active agents can bind to the surface of endothelial cells and enhance their susceptibility to killing by H2O2. Membrane-active agents which are capable of synergizing with H2O2 include cationic proteins, cationic poly-amino acids, lysophosphatides and enzymes which are capable of degrading membrane phospholipids (e.g., phospholipase C, phospholipase A2 and streptolysin S). In each case, treatment of the target cells with the membrane-active agent and H2O2 produces greater damage than the sum of the damage produced by either agent separately. Since inflammatory lesions, particularly sites of bacterial infection, may contain a rich mixture of cationic substances, phospholipases and phospholipid breakdown products, these substances may contribute to the tissue damage observed at sites of inflammation by enhancing endothelial cell sensitivity to PMN-generated H2O2 as well as by augmenting the generation of H2O2 by PMNs.
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PMID:Vascular endothelial cell killing by combinations of membrane-active agents and hydrogen peroxide. 255 61

Sultzer, Barnet M. (Princeton Laboratories, Inc., Princeton, N.J.), and Henry H. Freedman. Endotoxin-induced susceptibility to staphylococcal infection and its reversal by adrenergic blocking agents. J. Bacteriol. 90:1001-1006. 1965.-The transient phase of increased susceptibility to bacterial infection in mice provoked by prior administration of small doses of endotoxin was investigated for possible mediation by vasoactive substances. Animals were given endotoxin intravenously shortly before intraperitoneal injection of Staphylococcus aureus Smith, thereby lowering the lethal inoculum 10-fold. To determine whether this susceptibility state could be obviated, mice were pretreated with phenoxybenzamine or dibenzylchlorethylamine. Mortality decreased from an average of 81% in the endotoxin control groups to about 23% in the treated mice, closely approximating the mortality in control mice injected with saline and staphylococci. Neither antiadrenergic agent independently altered the resistance of mice to a higher lethal staphylococcal challenge, nor did these materials induce extravascular leukocyte mobilization into the peritoneal cavity. The results suggest a possible role of vasoactive staphylococcal alpha-toxin, as well as epinephrine or epinephrine-like factors, in this altered state of resistance to staphylococcal infection.
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PMID:Endotoxin-induced susceptibility to staphylococcal infection and its reversal by adrenergic blocking agents. 437 92

Fertilization includes sperm-oocyte recognition, adhesion, binding, fusion and egg activation. Integrin receptors, which are adhesion molecules, are expressed on sea urchin, mouse, hamster and human unfertilized oocytes. Potential sperm ligands have been identified. A role for integrins during fertilization is supported by inhibition of sperm-egg adhesion and/or fusion by means of anti-integrin monoclonal antibodies, Arg-Gly-Asp (RGD) or disintegrin-like peptides. In several cell-cell interactions, such as lymphocyte activation, viral fusion, bacterial infection or macrophage phagocytosis, integrins act as co-receptors after activation and, by clustering in a multimolecular complex, are able to transduce signals through cytoskeletal proteins and adaptor kinases. Experimental data suggest that they may act in a similar way during fertilization and may participate to initiation and/or propagation of the calcium signal via stimulation of phospholipase C gamma and inositol trisphosphate production.
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PMID:Role of integrins during fertilization in mammals. 1009 Oct 56

Bile supersaturation is necessary for cholesterol gallstones to form. Not all people with supersaturated bile form gallstones, however, and additional factors must be present. The role of pronucleating substances has been extensively studied. Of these, proteins, especially mucin, are best understood. Mucin is secreted by the gallbladder epithelium and may act as a nidus for crystal nucleation. Other proteins that may act as pronucleators include alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, phospholipase C, and a small calcium binding protein. The role of antinucleating factors is less well understood. Certain drugs, including octreotide and ceftriaxone, may also predispose to stone formation. Another local factor is gallbladder stasis, a well-known risk factor for pigment stone formation. More recent research has focused on the role of bacterial infection, which has long been believed to be a factor in pigment gallstone formation. Newer data also support a role for infection in cholesterol gallstone pathogenesis. Additionally, genetic factors that may predispose a patient to cholesterol gallstones have been identified in mice and in humans.
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PMID:Gallstone formation. Local factors. 1019 80

A central feature of Salmonella pathogenicity is the bacterium's ability to enter into non-phagocytic cells. Bacterial internalization is the consequence of cellular responses characterized by Cdc42- and Rac-dependent actin cytoskeleton rearrangements. These responses are triggered by the co-ordinated function of bacterial proteins delivered into the host cell by a specialized protein secretion system termed type III. We report here that SopB, a Salmonella inositol polyphosphatase delivered to the host cell by this secretion system, mediates actin cytoskeleton rearrangements and bacterial entry in a Cdc42-dependent manner. SopB exhibits overlapping functions with two other effectors of bacterial entry, the Rho family GTPase exchange factors SopE and SopE2. Thus, Salmonella strains deficient in any one of these proteins can enter into cells at high efficiency, whereas a strain lacking all three effectors is completely defective for entry. Consistent with an important role for inositol phosphate metabolism in Salmonella-induced cellular responses, a catalytically defective mutant of SopB failed to stimulate actin cytoskeleton rearrangements and bacterial entry. Furthermore, bacterial infection of intestinal cells resulted in a marked increase in Ins(1,4,5,6)P4, a consumption of InsP5 and the activation of phospholipase C. In agreement with the in vivo findings, purified SopB specifically dephosphorylated InsP5 to Ins(1,4,5,6)P4 in vitro. Surprisingly, the inositol phosphate fluxes induced by Salmonella were not caused exclusively by SopB. We show that the SopB-independent inositol phosphate fluxes are the consequence of the SopE-dependent activation of an endogenous inositol phosphatase. The ability of Salmonella to stimulate Rho GTPases signalling and inositol phosphate metabolism through alternative mechanisms is an example of the remarkable ability of this bacterial pathogen to manipulate host cellular functions.
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PMID:A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. 1113 47

Bacteria have evolved sophisticated regulatory circuits to modulate their gene expression in response to disparate environments. In order to monitor bacterial gene expression and regulation in the host, methods for direct transcript analysis from clinical specimens are needed. For most bacterial infections, amplification of the mRNAs of interest is necessary due to the low numbers of cells present and the low levels of specific transcripts. Here we compare two methods of quantitative reverse transcription-PCR (RT-PCR)-competitive RT-PCR using a one-tube system followed by standard gel analysis and the real-time detection of PCR product formation by fluorescence resonance energy transfer technology using the LightCycler unit. We isolated Staphylococcus aureus RNA directly from clinical specimens obtained from cystic fibrosis patients with chronic S. aureus lung infection and from an animal model of foreign-body infection with no further cultivation of the bacteria. Competitive RT-PCR and LightCycler RT-PCR were tested for their ability to quantify the transcription of a constitutively expressed gyrase gene (gyr) and a highly regulated alpha-toxin gene (hla) of S. aureus. Reproducible results were obtained with both methods. A sensitivity of 10(4) (gyr) and 10(3) (hla) copies, respectively, was reached, which was sufficient for the quantification of transcripts during bacterial infection. Overall, the competitive RT-PCR is a robust technique which does not need special RNA purification. On the negative side, it is labor intensive and time consuming, thus limiting the numbers of samples which can be analyzed at a given time. LightCycler RT-PCR is very susceptible to even traces of inhibitors, but it allows high-throughput processing of samples.
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PMID:Quantification of bacterial transcripts during infection using competitive reverse transcription-PCR (RT-PCR) and LightCycler RT-PCR. 1123 8

Skin infections with Staphylococcus aureus are not only an important cause of morbidity and even mortality, but are thought to serve as initiation and/or persistance factors for numerous inflammatory skin diseases, including psoriasis and atopic dermatitis. One mechanism by which S. aureus can modulate the immune system is through the production of proteins such as superantigenic toxins, Protein A, as well through the cytolytic alpha-toxin. This review serves to discuss the biology of these three types of proteins, with emphasis on their ability to stimulate the production of powerful pro-inflammatory lipid- and protein-derived cytokines in keratinocytes. Characterization of interactions between these proteins and the keratinocyte can provide a better understanding of how bacterial infection modulates inflammatory skin diseases, as well as provide the basis for improved therapies involving antibacterial agents.
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PMID:The keratinocyte as a target for staphylococcal bacterial toxins. 1192 32

Some data suggest that the central nervous system (CNS) is the main target of Staphylococcus alpha-toxin. Since this pathogen cannot penetrate the blood-brain barrier (BBB), the exact mechanism by which alpha-toxin affects the CNS remains unclear. Recent studies on the role of the innate immune system have shed light on how bacterial infections initiate inflammatory responses within the CNS. The aim of this study was to investigate the immunoexpression of Toll-like receptors (TLR 2, TLR 4) in brains of young rats systemically exposed to Staphylococcus alpha-toxin or injured by neonatal hypoxia-ischaemia. The study was carried out on 6-week-old Wistar rats. A group of 6-week-old rats with severe brain injury caused by neonatal hypoxia-ischaemia was also studied separately. In all control rats, the immunoexpression of TLR 2 and TLR 4 was not detected. However, the expression of both TLRs was evident in all brains injured by HI or exposed to alpha-toxin. The immunoexpression was localised in the wall of the small brain vessels, cells of ependyma and leptomeninges. In such vessels the spectrum of ultrastructural lesions was found. The presence of TLR4 detected in the nerve cells of the subcortical gray matter of the brain is particularly of interest, but requires further studies. The presence of TLR 4 antigen in the nerve cells of the subcortical gray matter is particularly of interest. In conclusion, the results show that brain microvessels through TLRs may participate in the immune response of brain affected by bacterial infection as well as injured by non-infection insults.
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PMID:Toll-like receptors in rat brains injured by hypoxic-ischaemia or exposed to staphylococcal alpha-toxin. 1553 30

The inositol 1,4,5-trisphosphate (IP3) content is decreased in soybean cells following infection with Pseudomonas syringae pv. glycinea (Psg). In this investigation, a differential display approach was applied to isolate soybean genes that are transcriptionally up-regulated by the inhibition of phosphoinositide-specific phospholipase C (PI-PLC) activity and to study if the transcription of those genes is altered following Psg infection. Four genes, transcriptionally activated following treatment with the PI-PLC-specific inhibitor U-73122, were cloned. Three of the four genes were induced following infection with Psg. The transcripts of a hydrolase homologue (GmHy) were induced in the incompatible but not compatible soybean-Psg interaction. The transcripts of a putative ascorbate oxidase gene (GmAO) were induced in both compatible and incompatible interactions. GmHy and GmAO may represent new classes of pathogenesis-related genes. In addition to these two novel genes, homologues of PR-10 and polygalacturonase inhibitor protein (GmPR10 and GmPGIP, respectively) were identified. These two genes have previously been reported as pathogenesis-related. Transcripts of GmPR-10, but not GmPGIP, were induced in both compatible and incompatible soybean-Psg interactions. Induction of these genes, except for GmPGIP, following inhibition of PI-PLC by either the U-73122 treatment or bacterial infection suggests that PI-PLC may negatively regulate the expression of defence genes.
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PMID:Inhibition of phosphoinositide-specific phospholipase C results in the induction of pathogenesis-related genes in soybean. 1557 Apr 70


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