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

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated which alpha 2-receptor subtypes are expressed in cultured cortical astroglia, and their coupling to second messengers. Binding assays using [3H]rauwolscine showed a very low number of alpha 2 receptors in the astrocytic cultures. Treatment of cultures with dibutyryl cyclic AMP (dBcAMP) increased significantly the number of receptors. The RNase protection assay was used to investigate which receptor subtype the cells express. The alpha 2B message was expressed at a low level in both treated and untreated cells, the levels of mRNA for the alpha 2A/D subtype were up-regulated significantly in cells treated with dBcAMP and no expression of mRNA for the alpha 2C subtype was detected. The alpha 2 agonist dexmedetomidine inhibited forskolin-induced increases in cyclic AMP both in treated and untreated cultures in a pertussis toxin-dependent manner. This effect was abolished by the alpha 2-receptor antagonist rauwolscine. Selective alpha 2-receptor agonists dexmedetomidine, clonidine, and UK14,304 all increased intracellular calcium only in dBcAMP-treated cells. The antagonist rauwolscine abolished this effect. Ca2+ responses were also seen in the absence of extracellular Ca2+ and they were inhibited by the phospholipase C inhibitor U-73122, suggesting that astroglial alpha 2 receptors are coupled to the inositol phospholipid pathway. We therefore also tested the effect of dexmedetomidine directly on inositol 1,4,5-trisphosphate accumulation. A significant increase was seen that was blocked by the antagonist rauwolscine and, as expected, by U-73122. In short, the results demonstrate that the alpha 2 receptors in astroglia are coupled to multiple second messenger pathways. They are up-regulated in cells treated with dBcAMP, which simultaneously assume a process-bearing morphology. If this morphological change reflects some in vivo process such as reactive gliosis, the up-regulation of alpha 2-receptor expression could mean an adaptive change in astrocytic responses to a common neurotransmitter, noradrenaline.
...
PMID:Coupling of astroglial alpha 2-adrenoreceptors to second messenger pathways. 863 62

Phospholipases form a ubiquitous class of enzymes optimized to catalyze the hydrolysis of phospholipids. Because their products are often second messengers, they are highly regulated by the cell. For a given ester bond, there are separate secreted as well as cytoplasmic phospholipases with different substrate specificities and modes of regulation. As it becomes available, structural information provides a view of interfacial catalysis for several of these phospholipases on a molecular level. Recent structural advances include solution structures of a pancreatic phospholipase A2 in the absence and presence of a micellar interface, crystal structures of a bacterial phosphatidylinositol-phospholipase C whose active site is reminiscent of ribonuclease, and a Ca2+ lipid binding domain with high homology to regions in several cytoplasmic phospholipases that can model the way those proteins interact with the membrane surface. Phospholipases also have a wide and complex array of regulatory mechanisms involving cytoplasmic proteins, notably G-proteins, as well as different effector lipids (e.g., phosphatidylinositol-4,5-biphosphate, or PIP2) or Ca2+. Deconvolution of these interactions is necessary to understand their roles in different signal transduction pathways.-Roberts, M. F. Phospholipases: structural and functional motifs for working at an interface.
...
PMID:Phospholipases: structural and functional motifs for working at an interface. 875 18

The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) beta receptors with mutations that eliminate activation of specific signalling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel alpha-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na+ channels while leaving the induction of type II alpha-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC gamma, GAP, and Syp abolished the induction of type II alpha-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na+ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na+ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.
...
PMID:Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation. 897 89

Expression of the hemolytic phospholipase C (PlcH) of Pseudomonas aeruginosa is induced under phosphate starvation conditions or in the presence of the osmoprotectants choline and glycine betaine. Because choline and glycine betaine may serve as carbon and energy sources in addition to conferring osmoprotection to P. aeruginosa, it seemed possible that induction of plcH is subject to catabolite repression control (CRC) by tricarboxylic cycle intermediates such as succinate. Total phospholipase (PLC) activity in osmoprotectant-induced cultures of P. aeruginosa PAO1 supplemented with 20 mM succinate was three- to fourfold lower than the levels in cultures supplemented with the non-catabolite-repressive substrate lactate. Analyses of osmoprotectant-dependent plcH expression in a derivative of strain PAO1 containing a plcH::lacZ operon fusion showed that (i) succinate prevented induction of plcH expression by osmoprotectants; and (ii) addition of succinate reduced or shut down further expression of plcH in osmoprotectant-induced bacteria, while cultures supplemented with lactate had little or no change in plcH expression. RNase protection analysis confirmed that repression of plcH occurs at the transcriptional level. However, a P. aeruginosa mutant decoupled in CRC exhibited a phenotype similar to that of the wild-type strain (PAO1) with respect to succinate-dependent repression of plcH expression. Osmoprotectant-induced total PLC activities, levels of expression of plcH measured with the same plcH::lacZ fusion, and levels of plcH transcription in a CRC-deficient strain reflected those seen in strain PAO1. This indicates that CRC of plcH functions by a distinct mechanism which differs from that regulating the glucose or mannitol catabolic pathway. A strain carrying a mutation in vfr, which encodes the Escherichia coli Crp homolog in P. aeruginosa, still exhibited a wild-type phenotype with respect to osmoprotectant-dependent expression and CRC of plcH. These data indicate that there is a novel CRC system that regulates the expression of plcH in P. aeruginosa.
...
PMID:Osmoprotectant-dependent expression of plcH, encoding the hemolytic phospholipase C, is subject to novel catabolite repression control in Pseudomonas aeruginosa PAO1. 924 77

PTH-induced mobilization of cytosolic Ca2+ in a human kidney cell line (HEK/W) occurring in the absence of cAMP stimulation was characterized and compared with that obtained in the same cells stably transfected by the PTH/PTH-related peptide (PTHrp) receptor (HEK/T). In both cell lines, N-terminal fragments of PTH and PTHrp induced a concentration-dependent biphasic stimulation in [Ca2+]i: a transient peak followed by a slow linear increase. These increases in [Ca2+]i were inhibited by the PTH antagonist [Nle(8,18),Tyr(34)]bPTH(3-34). The transient peaks were due to calcium release from intracellular stores, as they resisted quenching of calcium in the extracellular buffer and were abolished by prior emptying of intracellular stores. These peaks differed, however, both in latency period and in magnitude, in the two cell lines. The phospholipase C inhibitor U73122 inhibited the PTH-induced increase in [Ca2+]i in HEK/T cells, but not in HEK/W. Similarly, PTH-induced inositol phosphate (InsPs) production was detected in HEK/T but not in HEK/W cells. PTH-induced calcium release in HEK/W cells was inhibited by the simultaneous presence of ryanodine and U73122. Low level PTH/PTHrp receptor messenger RNA expression was demonstrated by ribonuclease protection in HEK/W cells, although no specific binding of [125I]PTHrP(1-34) could be detected. Amplification products for the PTH/PTHrp receptor 1, but no other isoforms, were detected by RT-PCR in HEK/W cells. As expected, HEK/T cells responded to PTH by a 500-fold stimulation in cAMP production and expressed large numbers of PTH/PTHrp receptors, as shown by [125I]PTHrp binding. These results demonstrate that the signal transduction pathways activated by PTH in HEK/W and HEK/T cells are different. Because the major difference in these cell lines is the number of PTH/PTHrp receptors expressed, these results suggest that the transduction of signals by the PTH/PTHrp receptor is controlled by receptor number in such a way that PTH stimulates an increase in intracellular calcium in the absence of stimulation of InsPs and cAMP production in cells expressing low levels of PTH/PTHrp receptor, but stimulates calcium release through an InsPs pathway and induces cAMP production in cells expressing large numbers of PTH/PTHrp receptors. The control of receptor number may be one of the mechanisms through which PTH effects are regulated.
...
PMID:Parathyroid hormone-induced calcium release from intracellular stores in a human kidney cell line in the absence of stimulation of cyclic adenosine 3',5'-monophosphate production. 938 12

A 58-kDa protein (ER58) was purified from monkey liver to apparent homogeneity. It accounts for more than 3% of microsomal proteins and is highly conserved among several mammalian species. The amino acid compositions of the N-terminal part and that of two internal peptide fragments present strong similarities with the sequence ascribed to phospholipase C-alpha. Numerous proteins exhibiting a high similarity with this sequence have been isolated by other investigators. Their biological function is controversial. Our purified protein is not active as a phosphatidylinositol-specific phospholipase C, protease or carnitine acyl transferase. Although less efficient than authentic protein-disulfide isomerase, ER58 catalyses the glutathione-dependent reduction of insulin and the reorganization of disulfide bonds of randomly oxidized (scrambled) ribonuclease in reducing conditions. In contrast, ER58 is devoid of oxidizing activity on thiol groups of reduced proteins. Many studies suggest that the proteins bearing the phospholipase C-alpha sequence could be considered as protein-disulfide isomerase isozymes. Our results indicate that ER58 is not totally similar to protein-disulfide isomerase in performing thiol :protein-disulfide oxidoreductase reactions and suggest that the two proteins may exert distinct cellular functions.
...
PMID:Purification of a 58-kDa protein (ER58) from monkey liver microsomes and comparison with protein-disulfide isomerase. 966 Feb

Chromatin phospholipidic fraction, as previously demonstrated, shows the same localization as RNA inside the nuclei. DNase and RNase treatment of nuclei removed almost totally the DNA, 63% of RNA and caused a 50% loss of phospholipids. The aim of the present investigation is to study the fraction of RNase undigested nuclear RNA and its relationship with the phospholipids still present in the nuclei. Isolated hepatocyte nuclei were treated with Triton X-100 and digested with RNase and DNase. The undigested nuclear material contained proteins (98%) and a small amount of RNA (1.7%), DNA (0.4%) and phospholipids (0.18%). The analysis of phospholipids showed the presence of two components only, namely phosphatidylcholine and sphingomyelin. In the same complex, the activity of sphingomyelin synthase, phosphatidylcholine-dependent phospholipase C and neutral sphingomyelinase has been detected. Treatment of isolated RNA with neutral sphingomyelinase modified the RNA in RNase sensitive RNA, thus suggesting that the SM may represent a bridge between two RNA strands possibly regulating transcription.
...
PMID:Nuclear sphingomyelin protects RNA from RNase action. 971 60

PIcR is a pleiotropic regulator of extracellular virulence factors in the opportunistic human pathogen Bacillus cereus and the entomopathogenic Bacillus thuringiensis, and is induced in cells entering stationary phase. Among the genes regulated by PIcR are: pIcA, encoding phosphatidylinositol-specific phospholipase C (PI-PLC); plc, encoding phosphatidylcholine-preferring phospholipase C (PC-PLC); nhe, encoding the non-haemolytic enterotoxin; hbl, encoding haemolytic enterotoxin BL (HBL); and genes specifying a putative S-layer like surface protein and a putative extracellular RNase. By analysing 37.1 kb of DNA sequence surrounding hbl, plcA and plcR, 28 ORFs were predicted. Three novel genes putatively regulated by PlcR and encoding a neutral protease (NprB), a subtilase family serine protease (Sfp) and a putative cell-wall hydrolase (Cwh) were identified. The corresponding sfp and cwh genes were located in the immediate upstream region of plcA and could both be regulated by a putative PlcR-binding site positioned between the inversely transcribed genes. Similarly, nprB was positioned directly upstream and transcribed in the opposite orientation to plcR. Genes surrounding plcA, plcR and hblCDAB that were lacking an upstream PlcR regulatory sequence did not appear to serve functions apparently related to PlcR and did not exhibit a conserved organization in Bacillus subtilis.
...
PMID:Sequence analysis of three Bacillus cereus loci carrying PIcR-regulated genes encoding degradative enzymes and enterotoxin. 1058 20

Secretion of Monocyte Chemotactic Protein-1 (MCP-1) by fibroblasts infected with Toxoplasma gondii was studied in vitro. A significantly higher MCP-1 secretion was observed 24 h after infection by live tachyzoites. Analysis of chemokine mRNA transcripts by RNase protection assay revealed that this MCP-1 secretion seems associated with increased MCP-1 mRNA expression. However, these increased levels of MCP-1 secretion and expression were not obtained after stimulation by heat-killed tachyzoites or parasites pre-treated by a specific inhibitor of phosphatidylcholine-specific phospholipase C (D609). Inhibition of parasite multiplication by pyrimethamine did not modify MCP-1 secretion. Thus, it appeared that the active penetration of T. gondii in cells was of major importance in the induction of MCP-1 secretion. None of the other chemokines studied by RNase protection assay (lymphotactin, RANTES, IP-10, MIP-1alpha, MIP-1beta, IL-8, and I-309) were expressed after infection by live tachyzoites. We also found that MCP-1 secretion induced by live T. gondii is blocked by inhibitors of nuclear factor (NF)-kappaB activation, ALLN and MG132. Such data indicate that NF-kappaB could be involved in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute to the recruitment of monocytes and lymphocytes and thus participate in the control of T. gondii infection and in its pathogenesis.
...
PMID:Toxoplasma gondii induces the secretion of monocyte chemotactic protein-1 in human fibroblasts, in vitro. 1094 4

Complement defense 59 (CD59) is a cell surface glycophosphoinositol (GPI)-anchored protein that prevents complement membrane attack complex (MAC) assembly. Here, we present evidence from ELISA assays that CD59 protein levels are significantly decreased in the frontal cortex and hippocampus of Alzheimer's disease (AD) compared with nondemented elderly (ND) patients, whereas complement component 9, a final component to form MAC, is significantly increased. To further confirm the CD59 deficit, PI-specific phospholipase C (PIPLC) was used to cleave the CD59 GPI anchor at the cell surface in intact slices from AD and ND cortex. CD59 released by PIPLC cleavage was significantly reduced in AD compared with ND samples. By the use of a ribonuclease protection technique, amyloid beta-peptide was found to downregulate CD59 expression at the mRNA level, suggesting a partial explanation of CD59 deficits in the AD brain. To evaluate the pathophysiological significance of CD59 alterations in neurons, we exposed cultured NT2 cells, which normally underexpress CD59, and NT2 cells transfected to overexpress CD59 to homologous human serum. Lactic acid dehydrogenase assays revealed significant complement-induced cell lysis in CD59-underexpressing NT2 cells and significant protection from such lysis in CD59-overexpressing NT2 cells. Moreover, cells expressing normal levels of CD59 showed no evidence of MAC assembly or damage after exposure to homologous serum, whereas pretreatment of these cells with a CD59-neutralizing antibody resulted in MAC assembly at the cell surface and morphological damage. Taken together, these data suggest that CD59 deficits may play a role in the neuritic losses characteristic of AD.
...
PMID:Deficiency of complement defense protein CD59 may contribute to neurodegeneration in Alzheimer's disease. 1102 7


<< Previous 1 2 3 4 5 Next >>

---