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 role of protein kinase C in ornithine decarboxylase (ODC; EC 4.1.1.17) gene expression in primary culture of newborn mouse epidermal cells (MEC) from BALB/c mice and in skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in female CD-1 mice was determined. A time course and the dose-response curves of ODC induction paralleled that of ODC mRNA induction by TPA in MEC. TPA treatment did not elicit any change in the size of ODC mRNA. The magnitude of ODC induction was proportional to the amount of ODC mRNA increased by TPA. TPA (2 X 10(-7) M) failed to induce ODC activity in MEC plated in Ca2+-deprived medium; TPA induction of ODC could be resumed upon Ca2+ restoration in the medium. 1-Oleoyl-2-acetylglycerol, a membrane-permeable diacylglycerol which activates protein kinase C, induced at the same rate both ODC activity and the amount of ODC mRNA in MEC. Phospholipase C, which releases diacylglycerol from membrane phospholipids, also induced ODC activity; 0.02 units of phospholipase C per ml led to about a 50-fold increase in ODC activity at 6 h after treatment. Phospholipase A2 was ineffective. Phospholipase C-induced ODC activity correlated with an increased level of ODC mRNA. Furthermore, palmitoylcarnitine, an inhibitor of protein kinase C, inhibited epidermal ODC induction and the increased level of ODC mRNA by TPA. Also, palmitoylcarnitine inhibited skin tumor promotion by TPA; application of 3 mumol of palmitoylcarnitine in conjunction with each promotional treatment with 10 nmol of TPA to the initiated skin of female CD-1 mice inhibited tumor formation. Taken together, we conclude that activation of protein kinase C may be an early event in ODC gene transcription and skin tumor promotion by TPA.
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PMID:Involvement of protein kinase C activation in ornithine decarboxylase gene expression in primary culture of newborn mouse epidermal cells and in skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 377 35

Several seven-carbon fatty acyl lecithins with varied acyl chain branching have been synthesized and characterized as potential phospholipase A2 substrates. Micellar bis(4,4-dimethylpentanoyl) phosphatidylcholine, bis(5-methylhexanoyl)phosphatidylcholine, bis(3-methylhexanoyl)phosphatidylcholine, and bis(2-methylhexanoyl)phosphatidylcholine are poor substrates for phospholipase A2 (Naja naja naja). These branched lecithins also inhibit the hydrolysis of diheptanoylphosphatidylcholine by the enzyme with Ki values comparable to or smaller than the apparent Km of the linear compound. The terminally branched lecithins are excellent substrates for another surface-active hydrolytic enzyme, phospholipase C from Bacillus cereus. When only one acyl chain bears a methyl group, the hybrid lecithins 1-heptanoyl-2-(2-methylhexanoyl)phosphatidylcholine and 1-(3-methylhexanoyl)-2-heptanoylphosphatidylcholine are substrates comparable to diheptanoylphosphatidylcholine. Analysis of micellar structure and dynamics by 1H and 13C NMR spectroscopy, quasi-elastic light scattering, and comparison of critical micellar concentrations indicates little significant difference in the conformation and dynamics of these seven-carbon fatty acyl lecithin micelles, even when the methyl groups are adjacent to the carbonyls. Phospholipase A2 UV difference spectra induced by phospholipid binding imply different enzyme conformations or aggregation states caused by linear-chain and asymmetric-chain lipids compared to bis(methylhexanoyl)phosphatidylcholines. The differences in hydrolytic activity of phospholipase A2 against the branched-chain micellar lecithins can then be attributed to an enzyme-lipid interaction at the active site. The species with both fatty acyl chains branched bind to phospholipase A2 but are not turned over rapidly. Since poor enzymatic activity only occurs for lecithins with both chains methylated, the interaction of both chains with the enzyme must be important for catalytic efficiency.
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PMID:Methyl branching in short-chain lecithins: are both chains important for effective phospholipase A2 activity? 398 78

Epididymal 5 alpha-reductase converts testosterone to 5 alpha-dihydrotestosterone. The enzyme is localized to the nuclear and microsomal membranes, and using two approaches, we investigated the relationship between 5 alpha-reductase activity and the membrane environment. In the first, nuclear and microsomal membrane fractions were treated with phospholipases to modify specifically the structure of the phospholipid component of the membranes, and the effects of these treatments on the kinetic parameters of 5 alpha-reductase were examined. The second approach was to observe the effects of phospholipids of known structure on solubilized 5 alpha-reductase activity. Treatment of the membrane fractions with phospholipase C increased the Km(app) of both the nuclear and microsomal 5 alpha-reductases for testosterone. Phospholipase A2 treatment also increased the Km(app) of the microsomal enzyme, but in contrast, the Km(app) of the nuclear 5 alpha-reductase for testosterone was unaffected. This demonstrated a fundamental difference in the role of the membrane environment in the expression of 5 alpha-reductase activity in these subcellular compartments. The ability of phospholipids to enhance the activity of solubilized 5 alpha-reductase was highly specific and structure related. Only phosphatidylcholines containing either unsaturated acyl chains or saturated acyl chains of 12 carbon atoms were found to activate 5 alpha-reductase. The most potent activator was dilauroyl phosphatidylcholine, which reduced the Km(app) values of both nuclear and microsomal 5 alpha-reductases for testosterone, without affecting the concentration of active 5 alpha-reductase (Vmax(app) ). This is the first time that an activator of 5 alpha-reductase has been found. These findings suggest that epididymal 5 alpha-reductase activity may be regulated by changes in the phospholipid environment.
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PMID:Modulation of epididymal delta 4-steroid 5 alpha-reductase activity in vitro by the phospholipid environment. 399 84

Using dimyristoyl L-alpha-phosphatidylcholine as a substrate, the effect of coenzyme Q10 on phospholipid digestion by phospholipase A2 and phospholipase C was investigated. Free myristic acids released by phospholipase A2, and myristic acids of dimyristoyl glyceride released by phospholipase C were methylated and determined quantitatively by gas-chromatography. Phospholipase A2 or phospholipase C released myristic acids dose-dependently from the substrate. Coenzyme Q10 prevented dose-dependently the hydrolysis of the substrate caused by phospholipase. These results suggest that pharmacological action of coenzyme Q10 could be attributed to its protection of membrane phospholipids against the attack of phospholipases.
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PMID:The effect of coenzyme Q10 on the action of phospholipase. 403 49

Treatment with phospholipase C strongly protected monkey kidney (Vero) cells against diphtheria toxin and reduced the ability of the cells to bind 125I-labelled toxin. Treatment with phospholipase D and with trypsin also protected the cells, although to a lesser extent. Phospholipase A2 had no protective effect. Phospholipase C also protected fetal hamster kidney cells against the toxin. After removal of the enzymes, as well as after treatment of the cells with 4-acetamide 4'-isothiocyanostilbene 2,2'-disulfonic acid, diphtheria toxin binding capability was restored slowly, apparently by a process requiring protein synthesis, since cycloheximide blocked the restoration. The data indicate that both phospholipids and protein are involved in the binding sites for diphtheria toxin.
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PMID:Evidence that membrane phospholipids and protein are required for binding of diphtheria toxin in Vero cells. 404 83

Protoplasts prepared from Bacillus subtilis by lysozyme digestion lysed in the presence of pure pancreatic phospholipase A(2). The phospholipids cardiolipin, phosphatidylethanolamine, phosphatidylglycerol and lysylphosphatidylglycerol, which are present in the membrane, are degraded by phospholipase A(2) only after removal of the cell wall, giving free fatty acids and lyso derivatives. The four phospholipids are hydrolyzed equally well at a given enzyme concentration. Differences in the phospholipid composition of the protoplasts were obtained by variations in the growth medium, time of harvesting, and preincubation time with lysozyme. The extent of hydrolysis appeared to depend on the initial phospholipid composition. A relative increase in acidic phospholipids in the membrane facilitated the action of phospholipase A(2), whereas the rate of hydrolysis was diminished when protoplasts were tested which contained a relatively high amount of positively charged phospholipid. Pure phospholipase C from B. cereus preferentially hydrolyzed phosphatidyl-ethanolamine in the B. subtilis membrane. More than 80% of this phospholipid was converted into diglyceride, whereas only 30% of the cardiolipin was hydrolyzed. Such a loss of phospholipids, however, was not followed by lysis of the protoplasts. Liposomes were prepared from the lipid extracts of B. subtilis and incubated with both phospholipases. The hydrolysis pattern of the phospholipids in these model membrane systems was identical to the hydrolysis pattern of the phospholipids in the protoplast membrane. Phospholipase A(2) hydrolyzed all the phospholipids in the liposomes equally well, whereas phospholipase C preferentially degraded phosphatidylethanolamine.
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PMID:Action of phospholipase A 2 and phospholipase C on Bacillus subtilis protoplasts. 462 52

The regulation of human platelet responses by cyclic AMP (cAMP) has been investigated by measuring thrombin-stimulated serotonin release, Ca2+ uptake and phospholipase activity. Thrombin-induced 1,2-diacylglycerol (DG) formation as a result of phospholipase C activation was inhibited by pretreatment with dibutyryl cAMP (dbcAMP) in a dose-dependent manner. Subsequent failure to produce phosphatidic acid (PA), which is converted from 1,2-DG by phosphorylation and would serve as intracellular Ca2+ ionophore, appeared to parallel the decrease in Ca2+ uptake activity. Phospholipase A2 activity, monitored by the production of [3H]lysophosphatidylcholine and [3H]lysophosphatidylethanolamine, was also suppressed by dbcAMP. These data indicate that the intracellular cAMP level may be closely associated with Ca2+ uptake and phospholipases activation. In addition, it is suggested that alteration of intracellular cAMP regulates phospholipase activation and consequently platelet responses, perhaps by controlling available Ca2+ content.
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PMID:Evidence that cyclic AMP may regulate Ca2+-mobilization and phospholipases in thrombin-stimulated human platelets. 630 29

Sarcolemmal membranes prepared by "gas dissection" from monolayers of cultured neonatal rat heart cells were studied with respect to their ability to bind calcium. Lanthanum displacement of calcium was 168 +/- 7 nmol/mg sarcolammel protein. This represents 3.21 mmol Ca/kg dry weight original cells on the basis of the measured membrane protein: dry cell weight ratio of 19.1 g/kg. Lanthanum-displaceable calcium from whole cells was essentially equal (3.32 mmol/kg dry weight), which indicates that all calcium displaceable from whole cells by lanthanum is localized to sarcolemmal sites. The potency of a series of divalent cations for calcium displacement from the sarcolemma was according to similarity of their crystal radii to that of calcium (cadmium greater than manganese greater than magnesium). This order was the same for the cations' ability to displace calcium from whole cells and for their ability to uncouple excitation from contraction in neonatal papillary muscle. The membranes were treated with four enzymes: phospholipase A2, phospholipase C, phopholipase D, and neuraminidase. Phospholipase A2 and phospholipase D produced significantly increased calcium-binding. The increased binding secondary to phospholipase A2 treatment was eliminated by an albumin wash which was indicative of binding to the fatty acid product of hydrolysis. The increase after phospholipase D treatment can be attributed to an increase in phosphatidate, with attendant increase in net anionic charge on the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of cations, phospholipases, and neuraminidase on calcium binding to "gas-dissected" membranes from cultured cardiac cells. 631 48

We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 production in a dose-dependent manner. At the maximal effective concentrations (0.5 unit of phospholipase A2/ml, 2 units of phospholipase C/ml), phospholipase C increased prostaglandin E2 formation to the level observed with phospholipase A2. Phospholipase A2 enhanced the release only of unsaturated fatty acids, whereas phospholipase C stimulated the release of individual free fatty acids (C 16:0, C 18:0, C 18:1, C 18:2 and C 20:4). Moreover, p-bromophenacyl bromide inhibited phospholipase A2-stimulated prostaglandin E2 production and the release of fatty acids, but it had no influence on prostaglandin E2 formation and the release of fatty acids increased by phospholipase C, indicating that the stimulatory effect of phospholipase C is not mediated through the activation of endogenous phospholipase A2. These results suggest the presence of diacylglycerol lipase and monoacylglycerol lipase in the kidney and the importance of this pathway in prostaglandin synthesis by the kidney.
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PMID:Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices. 658 1

The thiophospholipid 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC) was shown to be a mixture of two diastereomers by 31P nuclear magnetic resonance. The isomer that resonates at the lower field in CDCl3 (56.12 ppm) was designated as isomer A and the other (resonates at 56.07 ppm) as isomer B. Phospholipase A2 from four different sources (bee venom, Naja naja venom, Crotalus adamanteus venom, and porcine pancreas) was shown to hydrolyze the isomer B of DPPsC specifically, whereas phospholipase C from two different sources (Bacillus cereus and Clostridium perfringens) hydrolyzes isomer A specifically. So that the two diastereomers could be separated, DPPsC(A + B) was first digested with phospholipase A2 to give 1-palmitoyl-sn-glycero-3-thiophosphocholine (MPPsC) (which is designated as isomer B of MPPsC) and the unreacted DPPsC(A). Reacylation of MPPsC(B) gave pure DPPsC(B). The properties of DPPsC(A) and DPPsC(B) were investigated by 31P, 13C, 1H, and 14N nuclear magnetic resonance (NMR). 1H and 13C NMR showed that both isomers in methanol solution have conformational properties similar to those of the natural phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. On the other hand, the two isomers A and B showed small but significant differences in the chemical shifts of the carbon in the chiral carbon center and the phosphorus in the chiral phosphorus center.
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PMID:Phospholipids chiral at phosphorus. Preparation and spectral properties of chiral thiophospholipids. 668 28


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