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)

Glycosyl-inositolphospholipid (glycosyl-PtdIns) anchors of proteins in mammalian cells which have been analyzed so far are exclusively of the alkylacyl type. However, little is known about the putative precursor of glycosyl-PtdIns, the alkylacyl derivative of glycerophosphoinositol (GroPIns), in these cells since it is generally believed that cellular GroPIns consists of diacyl-type molecular species only. In this report, we describe the isolation and identification of alkylacyl GroPIns molecular species in both human and bovine erythrocytes, and compare it with the molecular species compositions of the glycosyl-PtdIns anchors of human and bovine erythrocyte acetylcholinesterase. Diradyl GroPIns was isolated from lipid extracts of ghost membranes and treated with phospholipase C. Diradylglycerols of the glycosyl-PtdIns anchors of affinity-purified human and bovine erythrocyte acetylcholinesterase were generated by sequential treatment with glycoprotein phospholipase D and acidic phosphatase and by PtdIns-specific phospholipase C, respectively. Diradylglycerols were subsequently converted into benzoate derivatives and separated into diacyl, alkylacyl, and alkenylacylglycerol subclasses. The molecular species compositions were quantitated and determined by combined HPLC/mass spectrometry. We found that human and bovine erythrocyte membrane diradyl GroPIns consist of 1.5-4.8% alkylacyl GroPIns. Molecular species analysis showed a heterogeneous species composition for both human and bovine erythrocyte alkylacyl GroPIns. Their compositions are distinctly different from those of human and bovine erythrocyte acetylcholinesterase glycosyl-PtdIns anchors. The number of alkylacyl GroPIns molecules/cell is roughly equal with the number of glycosyl-PtdIns-anchored proteins in human erythrocytes.
Eur J Biochem 1992 Sep 15
PMID:Alkylacyl glycerophosphoinositol in human and bovine erythrocytes. Molecular species composition and comparison with glycosyl-inositolphospholipid anchors of erythrocyte acetylcholinesterases. 139 75

The hypophase exchanger is a recently developed device that makes it possible to replace the liquid in the sample chamber of a pulsating bubble surfactometer, after a bubble has been formed, without changing the size of the bubble. A surfactant film outlining the bubble will retain its surface properties, provided the liquid entering the sample chamber and replacing the hypophase is inert. If, on the other hand, the new hypophase consists of a phospholipase solution, the physical properties of the film are seriously affected. It was found that when phospholipase C, even at low concentration, entered the sample chamber, the physical properties were significantly changed. Phospholipase A2 had to be added at a higher concentration to exert a similar effect. It is postulated that the site of action of phospholipase A2 may be partly protected in the hydrophobic region of the tightly packed surfactant film.
J Appl Physiol (1985) 1992 Sep
PMID:Phospholipases introduced into the hypophase affect the surfactant film outlining a bubble. 140 60

Increased expression of the potent vasoconstrictor and bronchoactive peptide, endothelin-1 (ET-1), has recently been demonstrated in airway epithelial and endothelial cells of asthmatic patients. To identify its potential role in contributing to airway smooth muscle (ASM) hyperplasia, a characteristic feature of asthmatic airways, the mitogenic action of ET-1 was investigated in cultured rabbit ASM cells. ET-1 elicited significant dose-dependent (10(-12)-10(-6) M) increases in ASM cell number, with a mean potency (i.e., -log mean effective dose) of action of 9.82-log M. ET-1 also acutely stimulated intracellular inositol 1,4,5-trisphosphate accumulation. The latter response was blocked by phospholipase C inhibition with neomycin; however, neomycin had no effect on the promitogenic action of ET-1. By contrast, the ASM cell proliferative response to ET-1 was independently inhibited by pertussis toxin, inhibitors of phospholipase A2, cyclooxygenase, and thromboxane A2 (TxA2) synthesis, as well as blockade of the TxA2 receptor. Moreover, in complementary studies, we found that administration of the stable TxA2 mimetics, carbocyclic TxA2 (CTA2) and U-46619, induced ASM cell proliferation and that ET-1 evoked the release of endogenous TxA2 from the ASM cells. Collectively, these observations provide new evidence that 1) ET-1 is a potent mitogen of ASM cells, 2) the promitogenic effect of ET-1 is associated with activation of a pertussis toxin-sensitive G protein coupled to stimulation of phospholipase A2, and 3) the latter mediates ASM cell proliferation via the release and autocrine mitogenic action of TxA2. The findings support a potential role for ET-1 in mediating the characteristic hyperplasia of ASM in asthma.
Am J Physiol 1992 Sep
PMID:Role of endothelin-1 in regulating proliferation of cultured rabbit airway smooth muscle cells. 141 57

We evaluated several potential effects of erythromycin (EM) on host defense systems and the virulence of Pseudomonas aeruginosa. Peritoneal macrophages obtained from mice given 250 mg of EM per kg of body weight for 7 days by the intraperitoneal, intravenous, subcutaneous, or oral route produced significantly greater amounts of thymocyte-activating factors. These data suggest that EM enhances the in vivo production of cytokines, such as interleukins 1 and 6. Treatment of P. aeruginosa D4 with subinhibitory concentrations of EM enhanced the association of bacteria with murine Kupffer cells in vitro and increased bacterial clearance from the blood in mice. EM suppressed the in vitro production of exotoxin A, total protease, elastase, and phospholipase C by P. aeruginosa D4; exotoxin A production by P. aeruginosa PA-103; and total protease production by P. aeruginosa B16 and PAO1 in a generally dose-dependent manner. These data demonstrate that EM produces various effects in addition to its direct antimicrobial activity, suggesting that it has potential as an immunomodulator or bacterial virulence-suppressing agent against P. aeruginosa and other infections.
Antimicrob Agents Chemother 1992 Sep
PMID:Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa. 141 82

The turnover of choline-containing phosphoglycerides (PC) in response to agonist stimulation is well documented in human neutrophils. We have now compared the enzymic pathways of N-formylmethionyl-leucylphenylalanine (fMLP)-, A23187- and phorbol-12-myristate 13-acetate (PMA)-induced diglyceride (DG) and phosphatidic acid (PA) generation in these cells. In order to distinguish between phospholipase C- and D-mediated PC breakdown, human neutrophils were radiolabelled with 1-O-[3H]alkyl-2-acyl-glycero-3-phosphocholine and stimulated in the presence of ethanol or propranolol. The addition of 0.5% ethanol to the incubation mixture resulted in the production of phosphatidylethanol, indicative of phospholipase D activation, in response to all three stimuli. Concomitant with phosphatidylethanol formation was a partial block of PA production. The production of DG was also partially blocked by addition of ethanol. Propranolol (200 microM) was also used to assess the contributions of phospholipases C and D toward DG generation. Inhibition of PA phosphohydrolase by propranolol resulted in the complete abolition of DG generation when neutrophils were stimulated with fMLP. In contrast, propranolol only partially inhibited DG generation in response to A23187 and PMA. These results suggested that DG production in response to fMLP stimulation is mediated via the activation of phospholipase D, whereas A23187- or PMA-induced DG generation may involve more than one pathway. However, examination of the water-soluble choline metabolites produced indicated that phospholipase D was responsible for the production of PA and DG in response to all three stimuli.
Biochem J 1992 Sep 15
PMID:Comparison of diglyceride production from choline-containing phosphoglycerides in human neutrophils stimulated with N-formylmethionyl-leucylphenylalanine, ionophore A23187 or phorbol 12-myristate 13-acetate. 141 27

The 12S oligomeric form of Staphylococcus aureus alpha-toxin has been studied with electron microscopy after incubation of the toxin with membrane preparations or liposomes. The target material originated from human platelets. Different electron microscopic preparation techniques were used including negative staining, freeze-fracture and vitrification in liquid ethane. Analysis of micrographs with image processing methods revealed two groups of ring-like structures corresponding to alpha-toxin oligomers. One form measured 75 A in diameter and had a high stain density in the central protein deficient part while the other was larger with a diameter of 100 A and less stain accumulation in the center. The conditions under which the latter were formed suggest that this corresponds to an inactive loosely-bound form of the toxin. The high stain density in the smaller particle is consistent with the presence of a penetrating pore in this structure.
FEMS Microbiol Immunol 1992 Sep
PMID:Oligomer formation of staphylococcal alpha-toxin analyzed by electron microscopy and image processing. 141 15

A DNA segment homologous to the third exons of the serotonin 1C and 2 receptor genes was isolated from a mouse genomic library. The positions of the introns flanking these exons were conserved in the three genes. To examine whether the new fragment was part of an active gene, we used a quantitative PCR protocol to analyse rat RNAs from different tissues and ages. The gene was expressed in stomach fundus at an abundance of 1 x 10(5) mRNA molecules. This tissue contracts in response to serotonin via a receptor that has previously resisted classification. We constructed a cDNA library from rat stomach fundus and isolated clones containing 2020 bp inserts with open reading frames of 465 amino acids comprising seven putative membrane-spanning regions. The protein was transiently expressed in COS cells and binding of serotonergic ligands to the membranes was analysed. The pharmacological profile resembled that described for the serotonin-stimulated contraction of the stomach fundus. After expression of this receptor in Xenopus oocytes, the application of serotonin triggered the typical chloride current which presumably results from the activation of phospholipase C. The coupling to this response system was less efficient than that of the 5-HT1C or 5-HT2 receptors.
EMBO J 1992 Sep
PMID:Cloning and functional characterization of the rat stomach fundus serotonin receptor. 150 25

A number of studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine (PC-PLC) both by growth factors and by the product of the ras oncogene, p21ras. Evidence has been presented indicating that the stimulation of this phospholipid degradative pathway is sufficient to activate mitogenesis in fibroblasts as well as that it is sufficient and necessary for induction of maturation in Xenopus laevis oocytes. However, the mechanism whereby PC-PLC transduces mitogenic signals triggered by growth factors or oncogenes remains to be elucidated. In this study, data are presented that show the involvement of protein kinase C zeta subspecies in the channelling of the mitogenic signal activated by insulin-p21ras-PC-PLC in Xenopus oocytes as well as the lack of a critical role of protein kinase C isotypes alpha, beta, gamma, delta, and epsilon in these pathways.
Mol Cell Biol 1992 Sep
PMID:Evidence for a role of protein kinase C zeta subspecies in maturation of Xenopus laevis oocytes. 150 83

NIH-3T3 cells were transfected with cDNA encoding the native alpha-subunit of the G protein Gq(alpha q) or a mutant (Q209L) form of alpha q. Cells expressing Q209L-alpha q showed greatly enhanced basal phospholipase C activity. Stimulation of phospholipase C activity by prostaglandin F2 alpha or fetal calf serum was increased up to 10-fold in Q209L-alpha q-transfected cells. Continuous expression of Q209L-alpha q or overexpression of alpha q in NIH-3T3 cells resulted in formation of foci after 3 weeks. The number of foci was proportional to the number of transfected cells and was greater in cells expressing the Q209L-alpha q than in cells that overexpressed the wild type alpha q. Q209L-alpha q-transfected NIH-3T3 cells also formed colonies in soft agar indicating their capacity to grow in an anchorage-independent manner. Expression of Q209L-alpha q in Rat-1 cells resulted in enhanced basal and fetal calf serum-stimulated phospholipase C activity, but these cells were not transformed as assessed by either the focus formation or the soft agar colony formation assays. These results indicate that expression of continuously activated Gq-alpha can result in transformation in a cell type-specific manner.
J Biol Chem 1992 Sep 15
PMID:Enhanced phospholipase C stimulation and transformation in NIH-3T3 cells expressing Q209LGq-alpha-subunits. 152 66

The protein tyrosine phosphatase (PTPase) inhibitor pervanadate (vanadyl hydroperoxide) stimulated protein tyrosine phosphorylation 29-fold more than did thrombin in intact and saponin-permeabilized platelets. Increased tyrosine phosphorylation preceded, or was coincident with, a fall in PtdIns(4,5)P2 levels, production of PtdIns(3,4)P2 and phosphatidic acid, mobilization of intracellular Ca2+, stimulation of protein kinase C-dependent protein phosphorylation, secretion of dense and alpha-granules, increased actin polymerization, shape change and aggregation which required fibrinogen and was mediated by increased surface expression of GPIIb-IIIa. The tyrosine kinase inhibitor RG 50864 totally prevented induction of tyrosine phosphorylation by pervanadate, as well as all other responses measured; in contrast, the inactive structural analogue, tyrphostin #1, had no effect. Dense-granule secretion induced by pervanadate required protein kinase C activity; however, aggregation and alpha-granule secretion were independent of protein kinase C. In saponin-permeabilized platelets pervanadate and thrombin stimulated phospholipase C activity by GTP-independent and GTP-dependent mechanisms respectively. We conclude that PTPases are important regulators of signal transduction in platelets.
Biochem J 1992 Sep 01
PMID:Activation of signal transduction in platelets by the tyrosine phosphatase inhibitor pervanadate (vanadyl hydroperoxide). 153 May 76


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