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)

The dependence of rabbit sciatic nerve PtdIns-specific phospholipase C activity Ca2+ and pH has been studied. The enzyme was found to hydrolyze PtdInsP2 in a Ca(2+)-dependent manner. The maximal activity was detected at 1mM CaCl2 for the cytosolic enzyme and at 0.1 mM CaCl2 for membrane-bound enzyme. The pH optima determined for the cytosolic and particulate enzymes were pH 6.0 and 7.0, respectively. The enzyme activity in the cytosolic fraction was shown to remain practically constant under nerve stimulation (200 impulses/sec, 5 min), whereas in microsomal fraction it was 44% greater compared to the resting nerve. It is suggested that the enzyme is bound to membrane in intact axon, therefore the rapid signal (depolarizing stimulus) transduction into axon becomes possible.
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PMID:[Activity of phosphoinositide-specific phospholipase C in rabbit nerves at rest and during stimulation]. 875 69

The histamine H1 receptor mediated increase in cytoplasmic Ca2+ ([Ca2+]i) was measured in the presence of the known phospholipase C (PLC) inhibitor, neomycin. Neomycin (1 mM) inhibited the histamine (100 microM) induced rise in [Ca2+]i to the same extent as observed after blocking Ca2+ entry with LaCl3. Likewise, the increase in [Ca2+]i after re-addition of CaCl2 (2 mM) to extracellular Ca2+ deprived and histamine pretreated cells was strongly reduced by neomycin. However, neomycin did not inhibit the histamine induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or the release of Ca2+ from internal stores. These results show that neomycin blocks histamine induced Ca2+ entry independent of phospholipase C activation. Inhibition of intracellular store Ca(2+)-ATPase by thapsigargin (1 microM), elicited an increase in [Ca2+]i due to a leakage from the stores, subsequently followed by store-dependent Ca2+ entry. Thapsigargin induced Ca2+ entry was also completely blocked by neomycin. These results indicate that neomycin inhibits histamine and thapsigargin induced Ca2+ entry. This inhibition is most likely exerted at the level of plasma membrane Ca2+ channels.
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PMID:Neomycin inhibits histamine and thapsigargin mediated Ca2+ entry in DDT1 MF-2 cells independent of phospholipase C activation. 881 55

Exposure to peroxides is known to increase the sensitivity of platelets towards activation by agonists. Similar platelet-activating effects are induced by sulfhydryl reagents that evoke Ca2+-induced Ca2+ release (CICR) by stimulating the Ca2+-releasing property of the inositol-1,4,5-trisphosphate receptor. We questioned whether these compounds may act by mobilising intracellular calcium in platelets by altering the intracellular glutathione redox state. Using FURA2-loaded, aspirin-treated platelets, Ca2+ signals were studied following exposure to the membrane-permeable sulfhydryl reagents, thimerosal and disulfiram, the glutathione peroxidase substrate, tert-butyl hydroperoxide, and the inhibitor of glutathione reductase, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In single platelets monitored by fluorescence imaging techniques, thimerosal and disulfiram elicited repetitive spiking in [Ca2+]i after variable lag times, indicating that these compounds stimulated CICR. BCNU caused [Ca2+]i spiking of only low amplitude, whereas tert-butyl hydroperoxide was inactive. In platelets in suspension devoid of extracellular CaCl2, the sulfhydryl reagents, at concentrations which decreased glutathione by 25%, strongly increased the Ca2+ responses of agonists that stimulated phospholipase C (thrombin) or acted independently of phospholipase C stimulation (thapsigargin). However, Ca2+ release was only slightly promoted by concentrations of BCNU that resulted in substantial depletion of the glutathione level. Tert-butyl hydroperoxide was without effect on glutathione, but partially inhibited Ca2+ mobilisation with these agonists. It is concluded that, in platelets, the potent CICR-promoting effects of sulfhydryl reagents are not solely due to their reaction with intracellular glutathione, but that extensive reduction in glutathione content is associated with Ca2+ mobilisation and CICR.
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PMID:Effect of membrane-permeable sulfhydryl reagents and depletion of glutathione on calcium mobilisation in human platelets. 926 Aug 81

Hydrolysis of 1-acyl-2-[14C]arachidonoyl-sn-glycero-3-phosphoethanolamine was studied in cerebral cortex homogenate and subcellular fractions. The enzyme(s) confined to the synaptic plasma membrane (SPM) hydrolyze(s) [14C-arachidonoyl]phosphatidylethanolamine (PE) in the presence of EGTA to [14C-arachidonoyl]diacylglycerol (DAG) and a small amount of [14C]arachidonic acid (AA). Degradation of PE is time-, protein- and substrate-dependent with a pH optimum of 7.8. The highest activity of PE degradation was observed in the presence of 10 mM EGTA. Under this condition GTP gamma S has no effect on PE hydrolysis. In the presence of Ca2+ ions degradation of PE was significantly lower as compared to the conditions with EGTA. However, the percentage distribution of free AA in the sum of both products of PE hydrolysis (AA + DAG) increases from 16 and 20% observed in the presence of EGTA 2 mM and 10 mM to 34% and 43% in the presence of 0.5 mM CaCl2 alone and together with GTP gamma S, respectively. Cytosolic enzymes also degrade PE in the presence of 2 mM EGTA with the formation of DAG and AA. Radioactivity in the AA represents about 80% of the total radioactivity of the products of PE degradation. The hydrolysis of PE by cytosolic enzymes is almost completely inhibited by neomycin but the hydrolysis by the SPM-bound enzyme(s) is inhibited only 70%. Other studies with quinacrine indicated that only a small pool of PE is degraded by SPM-bound Ca(2+)-independent phospholipase A2 (PLA2). All of these data suggest that PE in cerebral cortex is mainly degraded by cytosolic and SPM-bound Ca(2+)-independent phospholipase C. Further studies towards a better understanding of the mechanisms of cerebral degradation and the physiological significance of Ca(2+)-independent pathways of PE hydrolysis are necessary.
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PMID:Regulation of phosphatidylethanolamine degradation by enzyme(s) of subcellular fractions from cerebral cortex. 934 23

Magnaporthe grisea, the causal agent of rice blast, forms a dome-shaped melanized infection structure, an appressorium, to infect its host. Environmental cues that induce appressorium formation by this fungus include hydrophobicity and hardness of contact surface, and chemicals from the host. To determine if the calcium/calmodulin-dependent signaling systems are involved in appressorium formation in M. grisea, we tested the effects of the calcium chelator, calcium ionophore, diverse intracellular calcium modulators, and calmodulin antagonists on appressorium formation. Several calcium modulators and calmodulin antagonists inhibited appressorium formation at the microM level, while conidia germination remained unaffected. There was an inhibition of appressorium formation by EGTA, a calcium chelator, which was restored by the addition of exogenous CaCl2. Neomycin, a phospholipase C inhibitor, specifically inhibited appressorium formation at concentrations from 10 microM to 100 mM. These data suggest that a calcium/calmodulin-dependent signaling system is involved in the appressorium formation of M. grisea.
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PMID:Calcium/calmodulin-dependent signaling for appressorium formation in the plant pathogenic fungus Magnaporthe grisea. 989 22

The effect of econazole on intracellular calcium levels ([Ca2+]i) in Madin Darby canine kidney cells was investigated using fura-2 fluorimetry. Econazole increased [Ca2+]i dose-dependently at 5-50 microM. The Ca2+ signal consisted of an initial rise, a gradual decay and a sustained plateau. Extracellular Ca2+ removal partially reduced the econazole response. Mn2+ quench of fura-2 fluorescence confirmed econazole-induced Ca2+ influx. The econazole-sensitive intracellular Ca2+ store overlaps with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 25 microM econazole depleted the thapsigargin-sensitive store, and conversely, thapsigargin abolished the econazole response. Econazole (25-50 microM) partially inhibited capacitative Ca2+ entry induced by cyclopiazonic acid, another endoplasmic reticulum Ca2+ pump inhibitor, measured by depleting internal Ca2+ store in Ca(2+)-free medium followed by adding 10 mM CaCl2. Econazole induced capacitative Ca2+ entry itself. Pretreatment with La3+ (100 microM) partially inhibited 25 microM econazole-induced Mn2+ quench of fura-2 fluorescence, and La3+ immediately reduced 20 microM econazole-induced Ca2+ signal when added at the peak of the signal, suggesting that econazole induced Ca2+ influx via two separate pathways: one is sensitive to La3+, the other is not. La3+ enlarged 25 microM econazole-induced [Ca2+]i transient during the decay phase. The econazole response was not altered when the cytosolic level of inositol 1,4,5-trisphosphate was inhibited by the phospholipase C inhibitor U73122.
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PMID:Multiple effects of econazole on calcium signaling: depletion of thapsigargin-sensitive calcium store, activation of extracellular calcium influx, and inhibition of capacitative calcium entry. 999 Mar 6

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C. Cholinergic pathways are important in learning and memory, and deficits in cholinergic transmission have been implicated in Alzheimer's disease (AD). AD is also associated with increased beta-amyloid plaques. In the present study, we have investigated the effect of the amyloid beta (A beta) synthetic peptide homologous to residue 25-35 of A beta in nonaggregated and aggregated forms on the degradation of inositol phospholipids. Synaptic plasma membranes (SPM) and the cytosolic fraction from rat brain cortex served as a source of enzymes. The studies were carried out with radioactive inositol phospholipids in the presence of endogenous and 2 mM CaCl2. The enzyme(s) activity was evaluated by determination of the product formation of [3H]inositol-1-phosphate (IP1) or [3H]inositol-1,4,5-trisphosphate (IP3). Results show that the PI-PLC activity was significantly higher in cytosol compared to SPM, and this enzyme was stimulated by 2 mM CaCl2, but not by GTPgammaS or carbachol, a cholinergic receptor agonist. Activity of the SPM-bound PIP2-PLC was similar to that in cytosol and was not activated by 2 mM CaCl2. The SPM PIP2-PLC was significantly stimulated by GTPgammaS together with the cholinergic agonist, carbachol. Fresh-water-soluble A beta 25-35 activated PI-PLC in SPM markedly by two- to threefold, but this effect was absent in the presence of 2 mM CaCl2. Moreover, A beta 25-35 had no effect on basal PIP2-PLC activity and cytosolic PI-PLC and PIP2-PLC. The aggregated form of A beta 25-35 significantly inhibited PIP2-PLC only in the presence of endogenous CaCl2. It also inhibited the carbachol and GTP(gamma)S-stimulated PIP2-PLC. Our findings show that depending on the aggregation state and Ca2+ concentration, A beta modulates phosphoinositide degradation differently and exclusively in brain synaptic plasma membranes. Our data suggested that aggregated A beta peptide may be responsible for the significant impairment of phosphoinositide signaling found in brain membranes during AD.
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PMID:Amyloid beta peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex. 1052 54

The effect of miconazole on intracellular calcium levels ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells was studied using fura-2 as the Ca2+ indicator. Miconazole increased [Ca2+]i dose-dependently at concentrations of 5-100 microM. The [Ca2+]i transient consisted of an initial rise, a gradual decay and an elevated plateau (220 s after addition of the drug). Removal of extracellular Ca2+ partly reduced the miconazole response. Mn2+ quench of fura-2 fluorescence confirmed that miconazole induced Ca2+ influx. The miconazole-sensitive intracellular Ca2+ store overlapped with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 20 microM miconazole depleted the thapsigargin (1 microM)-sensitive store, and conversely, thapsigargin abolished miconazole-induced internal Ca2+ release. Miconazole (20-50 microM) partly inhibited the capacitative Ca2+ entry induced by 1 microM thapsigargin, measured by depleting intracellular Ca2+ store in Ca(2+)-free medium followed by addition of 10 mM CaCl2. Miconazole induced capacitative Ca2+ entry on its own. Pretreatment with 0.1 mM La3+ partly inhibited 20 microM miconazole-induced Mn2+ quench of fura-2 fluorescence and [Ca2+]i rise, suggesting that miconazole induced Ca2+ influx via two pathways separable by 0.1 mM La3+. Miconazole-induced internal Ca2+ release was not altered when the cytosolic level of inositol 1,4,5-trisphosphate (IP3) was substantially inhibited by the phospholipase C inhibitor U73122.
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PMID:Mechanisms of miconazole-induced rise in cytoplasmic calcium concentrations in Madin Darby canine kidney (MDCK) cells. 1062 36

Linoleamide is an endogenous lipid that has been shown to induce sleep in cats, rats and humans. However, its physiological function remains unclear. In this study the effect of linoleamide on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) tubular cells was examined, by using fura-2 as a Ca2+ probe. In a concentration-dependent manner, linoleamide induced increases in [Ca2+]i between 10-500 microM with an EC50 of 20 microM. The signal comprised a slow rise and a persistent phase, and was a result of internal Ca2+ release and external Ca2+ influx because it was partly inhibited by external Ca2+ removal. In Ca2+-free medium, depletion of the endoplasmic reticulum Ca2+ store with 1 microM thapsigargin abolished 100 microM linoleamide-induced internal Ca2+ release, and conversely, pretreatment with linoleamide prevented thapsigargin from releasing internal Ca2+. This demonstrates that the internal source of linoleamide-induced [Ca2+]i increase is located in the endoplasmic reticulum. This discharge of internal Ca2+ caused capacitative Ca2+ entry because after incubation with 100 microM linoleamide in Ca2+-free medium for 8 min readmission of 3 mM CaCl2 induced increases in [Ca2+]i. After the formation of inositol-1,4,5-trisphosphate (IP3) was blocked by the phospholipase C inhibitor U73122 (1 microM), linoleamide still induced an increase in [Ca2+]i but the shape of the increase was altered. Similar results were found for another sleep-inducing lipid 9,10-octadecenoamide. Together, the present study shows that the endogenous sleep-inducing lipid linoleamide was able to cause significant increases in [Ca2+]i in renal tubular cells, by releasing the endoplasmic reticulum Ca2+ store and triggering capacitative Ca2+ entry in a manner independent of IP3.
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PMID:Linoleamide, a brain lipid that induces sleep, increases cytosolic Ca2+ levels in MDCK renal tubular cells. 1121 75

The effect of nordihydroguaiaretic acid (NDGA) on Ca(2+) signaling in C6 glioma cells has been investigated. NDGA (5-100 microM) increased [Ca(2+)]i concentration-dependently. The [Ca(2+)]i increase comprised an initial rise and an elevated phase over a time period of 4 min. Removal of extracellular Ca(2+) reduced NDGA-induced [Ca(2+)]i signals by 52+/-2%. After incubation of cells with NDGA in Ca(2+)-free medium for 4 min, addition of 3 mM CaCl2 induced a concentration-dependent increase in [Ca(2+)]i. NDGA (100 microM)-induced [Ca(2+)]i increases in Ca(2+)-containing medium was not changed by pretreatment with 10 microM nifedipine or verapamil. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM) abolished 100 microM NDGA-induced [Ca(2+)]i increases. Inhibition of phospholipase C with 2 microM U73122 had little effect on 100 microM NDGA-induced Ca(2+) release. Several other lipoxygenase inhibitors had no effect on basal [Ca(2+)]i. Collectively, the results suggest that NDGA increased [Ca(2+)]i in glioma cells in a lipoxygenase-independent manner, by releasing Ca(2+) from the endoplasmic reticulum in a manner independent of phospholipase C activity and by causing Ca(2+) influx.
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PMID:Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in C6 glioma cells. 1174 Oct 8


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