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 proteolipid able to bind phosphate has been isolated from yeast mitochondria. During the purification the active protein was always associated with cardiolipin. The cardiolipin requirement for the phosphate binding activity of this proteolipid has been studied using controlled lipid depletion with two phospholipases A2 and with phospholipase C. Only phospholipase A2 from pig pancreas, that deacylated cardiolipin, promoted inhibition of the proteolipid activity (but never more than 70 per cent). Phospholipase A2 from snake venom did not inhibit the binding activity of the proteolipid. Using thin layer chromatography with two sequential solvents it was possible to separate two cardiolipin subspecies; one of them was preferentially hydrolysed by phospholipase C of Bacillus cereus, leading to inhibition of the proteolipid activity. Ca2+ complexed to cardiolipin stoichiometrically (1-1) inhibited the proteolipid activity. This effect could be due to a conformational change in the cardiolipin-protein association.
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PMID:Cardiolipin-protein interactions in the phosphate binding activity of a proteolipid from yeast mitochondria. Action of phospholipases A2 and C and of cations. 681 19

Rat gastric mucosa homogenates contain two enzymatic systems for hydrolyzing phosphatidylinositol: a deacylation activity yielding lysophosphatidylinositol and free fatty acid, and a phospholipase C-like activity producing 1,2-diacylglycerol and inositol phosphates. These activities were found mainly in the 105 000 x g supernatant and could be distinguished by differential stabilities, metal requirements and the action of deoxycholate and mepacrine. Each lipolytic reaction displayed a major pH optimum at 7.5 and a minor pH optimum at 5.5. The deacylation system was 8-10 times as active as the phospholipase C, with an apparent Km of 0.63 mM towards 1-acyl-2-arachidonylphosphatidylinositol at pH 7.5. The phospholipase C activity, on the other hand, hydrolyzed 1-acyl-2-arachidonylphosphatidylinositol or 1-acyl-2-arachidonylphosphatidylethanolamine and yielded 1-acyl-2-arachidonyl-sn-glycerol. This 1,2-diacylglycerol could be phosphorylated to form 1-acyl-2-[14C]arachidonyl-sn-phosphoglycerol (phosphatidic acid), but could not be hydrolyzed to produce free [14C]arachidonic acid using stomach mucosal microsomes. Phospholipase A2 and phospholipase C attack 1-acyl-2-arachidonylphosphatidylethanolamine and phosphatidylinositol equally well, but hydrolyze 1-acyl-2-arachidonylphosphatidylcholine poorly.
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PMID:Degradation of phosphatidylinositol by soluble enzymes of rat gastric mucosa. 702 17

Inside-out vesicles (IOV) were prepared from human red blood cells. Steady-state uptake of 23Na was observed to generally follow an exponential time course with a rate constant of 1.57 +/- 0.09 h-1 (SE). One week of cold storage (0-4 degrees C) increased the rate constant to 2.50 +/- 0.12 h-1 (SE). Mg2+, Ca2+, or Sr2+ decreased the rate of 22Na uptake with no observable differences between the three divalent cations when tested at concentrations of 50 microM. Mg2+ was shown to decrease the rate of 22Na uptake at concentrations as low as 5 microM with maximal effect at 50 to 100 microM. The decrease in rate of 22Na uptake induced by Mg2+ could be enhanced by exposure of IOV to Mg2+ for longer periods of time. Trypsin treatment of OIV increased the rate of uptake of 22Na and was dependent on the concentration of trypsin added between 5 to 25 micrograms/ml (treated for 5 min at 25 degrees C). The ability of Mg2+ (50 microM) to decrease the rate of 22Na uptake was still observed after maximal trypsin treatment. Phospholipase A2 or phospholipase C treatment of IOV increased the rate of 22Na uptake and was dependent on the amount of phospholipase A2 (0.1 to 1.0 units/ml) or phospholipase C (0.25 to 2.5 units/ml) added (treated for 5 min at 25 degrees C). After phospholipase A2 treatment, the observed decrease in the rate of 22Na uptake induced by Mg2+ (50 microM) was generally greater than controls. After phospholipase C treatment, the observed decrease in rate of 22Na uptake induced by Mg2+ (50 microM) was less or absent when compared with controls. Phospholipase C treatment was less effective in preventing the Mg2+ effect the longer IOV were exposed to Mg2+. The results suggest that Mg2+ binds to phospholipid headgroups to reduce Na permeability perhaps by inducing a change in bilayer structure or phospholipid association.
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PMID:Effects of divalent cations, trypsin, and phospholipases on the passive permeability to sodium of inside-out vesicles from human red cells. 706 86

The role of rat liver plasma membrane phospholipids in the regulation of protein kinase A, protein kinase C and tyrosine kinase activities was investigated. Plasma membrane composition was modified by phospholipase A2, phospholipase C and phospholipase D treatment and subsequent incorporation of various phospholipids. Phospholipase A2 deactivated the three types of protein kinases, while phospholipase C and D affected the enzymes in a different manner. Phosphatidylcholine and sphingomyelin were found to be the most effective activators of protein kinase A and tyrosine kinase. Incorporation of sphingomyelin and phosphatidylserine into partially delipidated plasma membranes resulted in a significant stimulation of protein kinase C activity. Since sphingomyelin appeared to be a specific effector of the three types of protein kinases under investigation, one might suggest that its role in cellular signaling could be manifested via regulation of protein kinase C as well as via modulation of protein kinase A and tyrosine kinase activities.
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PMID:Role of rat liver plasma membrane phospholipids in regulation of protein kinase activities. 755 80

Phospholipase A2 (PLA2) is a key enzyme in the release of arachidonic acid and subsequent production of eicosanoids, which play an important role in a variety of biological processes, including mitogenic signalling by epidermal growth factor (EGF). In a previous study [Spaargaren, M. et al. (1992) Biochem J. 287, 37-43] we identified the EGF-activated PLA2 as being similar to the recently cloned high-molecular-mass cytosolic phospholipase A2 (cPLA2). In the present study we demonstrate a rapid transient EGF-induced activation of this cPLA2 and an EGF-induced increase in phosphorylation of the cPLA2. The EGF-induced activation of cPLA2 is reversed upon phosphatase treatment showing phosphorylation-dependent activation of the cPLA2. No direct association of the cPLA2 to the EGF receptor was detected under conditions where such an association with phospholipase C-gamma was demonstrated. Phosphoamino acid analysis of this cPLA2 showed that EGF induced an increase in serine phosphorylation exclusively, no tyrosine phosphorylation being observed. EGF treatment of the cells resulted in a Ca(2+)-dependent translocation of the cPLA2 from the cytosol to the membrane fraction. This is due to an EGF-induced [Ca2+]i rise which is dependent on the influx of extracellular Ca2+ via voltage-independent Ca2+ channels. It is shown that the Ca(2+)-dependent association of cPLA2 to membranes does not require accessory membrane molecules.
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PMID:Epidermal growth factor (EGF) induces serine phosphorylation-dependent activation and calcium-dependent translocation of the cytosolic phospholipase A2. 764 58

Phospholipase A2 (PLA2) toxins act presynaptically to block acetylcholine release and are much more potent and specific in their actions than PLA2 enzymes even though they have lower enzymatic activity. Since their mechanism of action is not completely understood, it was of interest to examine the toxins' effects on phospholipid asymmetry as changes in asymmetry are associated with changes in membrane functioning. Rat brain synaptosomes were treated with the PLA2 toxins beta-bungarotoxin (beta-BuTx) and notexin and with the PLA2 enzymes Naja nigricollis and Naja naja atra under relatively non-disruptive conditions as judged by leakage of lactate dehydrogenase (LDH) and levels of phospholipid hydrolysis. The exposure of phosphatidylcholine (PC) and phosphatidylinositol (PI) on the synaptosomal surface was investigated by means of a specific PC-exchange protein (PCEP) and a PI-specific phospholipase C (PI-PLC), respectively. Treatment of the synaptosomes with N. nigricollis PLA2, beta-BuTx and notexin did not affect the availability of PC to exchange by PCEP, but significantly increased the exposure of PI to hydrolysis by PI-PLC. In contrast, N. n. atra PLA2 slightly decreased the exposure of PC and did not affect that of PI. The differences between N. n. atra PLA2, on the one hand, and N. nigricollis PLA2, beta-BuTx and notexin, on the other hand, parallel differences in their pharmacological activities. Our earlier studies showed that PLA2 enzymes, and possibly PLA2 toxins, have a pharmacological site separate from the enzymatic site. Since in the present study the effect on PI was abolished by EDTA, the presence of an enzymatic site in addition to the pharmacological site may be required or alternatively divalent cations may be required for the effects on PI asymmetry independent of the inhibition of PLA2 by EDTA.
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PMID:Exposure of phosphatidylcholine and phosphatidylinositol in plasma membranes from rat brain synaptosomes treated with phospholipase A2 toxins (beta-bungarotoxin, notexin) and enzymes (Naja nigricollis, Naja naja atra). 794 May 75

Phospholipase A2 activity was measured in cerebral microvessels isolated from 5 to 6 month (young adult) and 21 to 24 month (aged adult) old mice. Radiolabeled 1-stearoyl-2-[1-14C]arachidonyl choline phosphoglyceride was used as the enzyme substrate, and enzyme activity determined at pH 8 and pH 9. Activity in older animals was significantly less than in younger animals at both pH's. With choline phosphoglyceride as a substrate, phospholipase A2 activity was predominantly Ca(2+)-dependent, although a small, but measurable Ca(2+)-independent component was present. Negligible production of diacylglycerol indicated little or no phospholipase C activity. These findings indicate that activity of a phospholipase A2, which utilizes choline phosphoglyceride as a substrate, is affected by the aging process. Moreover, a change in PLA2 activity would result in altered metabolism of specific phosphoglycerides and turnover of fatty acids at the sn-2 position in cerebral microvessels.
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PMID:Cerebral microvessel phospholipase A2 activity in senescent mouse. 817 71

The potential involvement of ceramide-related signaling processes in the induction of apoptosis by tumor necrosis factor alpha was assessed by multiple biochemical strategies in the human leukemic cell lines HL-60 and U937 and the murine fibrosarcoma cell lines L929/LM and WEHI 164/13. Exposure of these cells to tumor necrosis factor alpha resulted in internucleosomal cleavage of genomic DNA, yielding laddered patterns of oligonucleosomal fragments characteristic of apoptosis when resolved by agarose gel electrophoresis; similar responses were observed after exposure to exogenous sphingomyelinase or synthetic ceramides. Quantitative spectrofluorophotometry demonstrated that these treatments promoted time- and concentration-dependent degradation of DNA, resulting in the formation of and eventual release of small DNA fragments (< or = 3.0 kb). Corresponding damage to bulk DNA was demonstrated by enhanced-fluorescence alkaline unwinding analysis. DNA fragmentation was not induced by phospholipase C or synthetic diglyceride; in fact, the effects of sphingomyelinase and ceramide were substantially reduced by coexposure to these agents, suggesting opposing roles for diglyceride- and ceramide-mediated signals in the regulation of apoptosis. Phospholipase A2 and arachidonic acid failed to promote DNA fragmentation, as did phospholipase D. Characterization of DNA strand breaks by alkaline and neutral elution analyses confirmed that ceramide action was restricted to breakage of mature, double-stranded DNA but not of nascent DNA. The induction of DNA damage was associated with appearance of apoptotic morphology and decreased clonogenicity. These results demonstrate that the ceramide-dependent signaling system selectively induces apoptosis and raise the possibility that ceramide-activated enzymes represent important components in a signaling cascade involved in the regulation of programmed cell death.
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PMID:Induction of apoptotic DNA damage and cell death by activation of the sphingomyelin pathway. 827 10

The effects of protein kinase C activation on phospholipase A2 and phospholipase C activity in permeabilised cultured myometrial cells from guinea pig uterus have been studied. Phospholipase A2 activity was followed by measurement of [3H]arachidonic acid release from [3H]arachidonic acid-prelabelled membrane lipids. [3H]Arachidonic acid release was stimulated by Ca2+ at 1-10 microM and by GTP gamma S at 1 microM to 1 mM in the presence of 10 microM Ca2+. The activation by calcium was enhanced 89.5 +/- 12.7% (P < 0.01) in the presence of 1 microM phorbol 12-myristate 13-acetate (PMA) and that by 1 microM GTP gamma S by 65.4 +/- 4.4% (P < 0.001). The PMA enhancement of arachidonic acid release was completely blocked by 3 microM staurosporine. Phospholipase C activation was followed by measurement of [3H]inositol polyphosphate production from [3H]inositol-prelabelled membrane lipids. This was stimulated by Ca2+ at 0.1 and 10 microM and by 1 and 50 microM GTP gamma S. PMA at 1 microM caused a consistent reduction in the extent of Ca2+ and GTP gamma S-stimulated inositol polyphosphate production and 3 microM reversed the inhibitory action of PMA. The data are consistent with arachidonic acid release in permeabilised myometrial cells from guinea pigs reflecting in large part phospholipase A2 activation and with that pathway being stimulated by protein kinase C activation. They are also consistent with protein kinase C activation causing reduction in phospholipase C pathways in uterine myocytes, at least as measured by inositol polyphosphate release.
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PMID:Modulation by protein kinase C of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus. 835 48

Isolated hippocampal mossy fiber synaptosomes were used to characterize control mechanisms of prostaglandin F2 alpha (PGF2 alpha) synthesis at a central mammalian synapse. Exogenous arachidonic acid stimulated the dose-dependent synthesis of PGF2 alpha, as did the addition of phospholipase A2 or the activation of endogenous phospholipase A2. Phospholipase A2 inhibitors attenuated prostaglandin synthesis, but phospholipase C inhibitors had no effect. However, a diglyceride kinase inhibitor reduced PGF2 alpha accumulation. The cyclooxygenase inhibitor ibuprofen eliminated PGF2 alpha production, while the lipoxygenase inhibitors baicalein and NDGA reduced PGF2 alpha accumulation. The CA(2+)-ionophore-dependent stimulation of PGF2 alpha synthesis was abolished by Cd2+ or Ni2+. Further more, PGF2 alpha production appeared to be dependent on Ca2+ influx via L-type, but not N- or T-type, voltage-sensitive Ca2+ channels. Membrane depolarization with KC1, veratridine or 4-aminopyridine stimulated the synthesis of PGF2 alpha. This depolarization-dependent stimulation of PGF2 alpha synthesis was attenuated by L-type voltage-sensitive Ca2+ channel blockers, phospholipase A2 inhibitors, a K+ channel activator and a Na+ channel blocker. The activation of protein kinase C also led to a reduction of PGF2 alpha accumulation in depolarized nerve endings. These results may be used to suggest that PGF2 alpha production by hippocampal mossy fiber synaptosomes was controlled by the Ca(2+)- and phospholipase A2-dependent accumulation of unesterified arachidonic acid and was modulated by membrane depolarization and the activity of protein kinase C.
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PMID:Prostaglandin F2 alpha synthesis in the hippocampal mossy fiber synaptosomal preparation: I. Dependence in arachidonic acid, phospholipase A2, calcium availability and membrane depolarization. 844 49


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