Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4-Hydroxynonenal (HNE), a major lipid peroxidation product, displays several biological actions. Among them, the differentiation of human HL-60 cells and the stimulation of neutrophil oriented migration occur at concentrations which can be actually found in normal tissues and in body fluids. In spite of its chemotactic activity, HNE fails to increase neutrophil oxidative metabolism. The action of the aldehyde on cell migration appears to be mediated by a phosphoinositide specific phospholipase C. The acceleration of phosphatidylinositol turnover induced by 10 pM 4-hydroxyoctenal, another lipid peroxidation product, is prevented by the pretreatment of neutrophils with pertussis toxin. The mechanism of action of these 4-hydroxyalkenals appears to follow pathways common to other chemoattractants, but some differences can be found too. In particular HNE seems unable to stimulate phospholipase D activity. The action of 4-hydroxyalkenals and other lipid peroxidation products on transmembrane signalling systems and on phospholipid metabolism might regulate several cell functions, such as motility, proliferation and differentiation.
Mol Aspects Med 1993
PMID:Action of lipid peroxidation products on phosphoinositide specific phospholipase C. 826 43

When administered in the diet to third instar Drosophila melanogaster larvae, short chain primary alcohols reduce phosphatidylcholine (PC) levels. The ethanol-induced reductions in larval PC may be in part due to an increase in the activity of PC-specific phospholipase D (PC-specific PLD, EC 3.1.4.4). PC-specific PLD not only hydrolyzes PC, but it also apparently catalyzes the formation of phosphatidylethanol. PC-specific PLD activity was also stimulated by 200 mM ethanol, methanol, isopropanol, n-butanol, and n-propanol. In vitro studies indicated that Drosophila PC-specific PLD activities were enhanced by submicromolar concentrations of Ca2+ and by GTP-gamma S. In vivo studies utilizing [14C]lyso-palmitoyl phosphatidylcholine indicated that dietary ethanol promoted the flux of label into triacylglycerol, 1,2 diacylglycerol, and fatty acid ethyl esters, while the label in PC decreased.
Insect Biochem Mol Biol 1993 Sep
PMID:Dietary ethanol stimulates the activity of phosphatidylcholine-specific phospholipase D and the formation of phosphatidylethanol in Drosophila melanogaster larvae. 835 29

The tegument of trematodes serves as a dynamic host-parasite interface where surface antigens are shed in a process of immune evasion. Phospholipases, which could provide an enzymatic mechanism for release of glycosylphosphatidylinositol (GPI)-anchored proteins, were detected in detergent extracts of adult worms of Fasciola hepatica and cercaria and adult worms of Schistosoma mansoni. The enzymatic activities were partially characterized from both adult worm species and demonstrated a preference for [3H]GPI substrate over [3H]PI. Lipase activities from both species were sensitive to sulfhydryl-modifying reagents and the detergents CHAPS and n-octylglucoside. The presence of 1 M ammonium sulfate increased the enzyme activity in adult worms of both species by 8-11-fold and in cercaria by 146-fold, whereas other conditions of high ionic strength were inhibitory. Such stimulation suggested dissociation of a negative inhibitor which is prominent in the cercarial stage. The schistosome extract, which was partially sensitive to cation chelators and o-phenanthroline, contained a GPI-phospholipase D activity. In contrast, the F. hepatica extract contained a cation-independent phospholipase C activity which was partially purified and shown by gel filtration to have a molecular mass of 30,000-80,000.
Mol Biochem Parasitol 1993 May
PMID:Detection and partial characterization of glycosylphosphatidylinositol-specific phospholipase activities from Fasciola hepatica and Schistosoma mansoni. 839 Jun 13

The hydrolysis of phospholipids in vasopressin-stimulated baby hamster kidney (BHK)-21 and H9c2 myoblastic cells was investigated. Phosphatidylcholine and phosphatidylethanolamine in these cells were pulse labelled with [3H]glycerol, [3H]myristate, [3H]choline or [3H]ethanolamine, and chased with the non-labelled precursor until linear turnover rates were obtained. When cells labelled with [3H]glycerol or [3H]myristate were stimulated by vasopressin, no significant decrease in the labelling of phosphatidylcholine was detected, but the labelling of phosphatidic acid was elevated. However, the labellings of phosphatidylethanolamine and its hydrolytic product were not affected by vasopressin stimulation. When the cells were pulse labelled with [3H]-choline, vasopressin stimulation caused a decrease in the labelled phosphatidylcholine with a corresponding increase in the labelled choline. The apparent discrepancy between the two types of labelling might be explained by the recycling of labelled phosphatidic acid back into phosphatidylcholine, thus masking the reduction in the labelled phospholipid during vasopressin stimulation. Alternatively, the labelled choline produced by vasopressin stimulation was released into the medium, thus reducing the recycling of label precursor back into the phospholipid and making the decrease in the labelling of phosphatidylcholine readily detectable. Further studies revealed that vasopressin treatment caused an enhancement of phospholipase D activity in these cells. The presence of substrate-specific phospholipase D isoforms in mammalian tissues led us to postulate that the differential stimulation of phospholipid hydrolysis by vasopressin was caused by the enhancement of a phosphatidylcholine-specific phospholipase D in both BHK-21 and the H9c2 cells.
Mol Cell Biochem 1995 Oct 04
PMID:Enhancement of phospholipid hydrolysis in vasopressin-stimulated BHK-21 and H9c2 cells. 858 16

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, renal tubular dysfunction and neurological deficits. The gene responsible for this disorder, OCRL-1, has been cloned and mutations identified in patients. The gene product (ocrl-1) has extensive sequence homology to a 75 kDa inositol polyphosphate 5-phosphatase. We report here that OCRL patients' fibroblasts show no abnormality in inositol polyphosphate 5-phosphatase activity, but are deficient in a phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] 5-phosphatase activity localized to the Golgi apparatus. Direct biochemical diagnosis of this human disease should now be possible. PtdIns(4,5)P2 has been implicated in Golgi vesicular transport through its role in the regulation of ADP-ribosylation factor, phospholipase D and actin assembly in the cytoskeleton. The regulation of PtdIns(4,5)P2 levels by PtdIns(4,5)P2 5-phosphatase may, therefore, be important in the modulation of Golgi vesicular transport. Given that the primary defect in OCRL is a deficiency of a Golgi PtdIns(4,5)P2 phosphatase, we hypothesize that the disorder results from dysregulation of Golgi function and in this way causes developmental defects in the lens and abnormal renal and neurological function.
Hum Mol Genet 1995 Dec
PMID:Lowe syndrome, a deficiency of phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. 863 94

There is now clear evidence that receptor-dependent phospholipase D is present in myocardium. This novel signal transduction pathway provides an alternative source of 1,2-diacylglycerol, which activates isoforms of protein kinase C. The members of the protein kinase C family respond differently to various combinations of Ca2+, phosphatidylserine, molecular species of 1,2-diacylglycerol and other membrane phospholipid metabolites including free fatty acids. Protein kinase C isozymes are responsible for phosphorylation of specific cardiac substrate proteins that may be involved in regulation of cardiac contractility, hypertrophic growth, gene expression, ischemic preconditioning and electrophysiological changes. The initial product of phospholipase D, phosphatidic acid, may also have a second messenger role. As in other tissues, the question how the activity of phospholipase D is controlled by agonists in myocardium is controversial. Agonists, such as endothelin-1, atrial natriuretic factor and angiotensin II that are shown to activate phospholipase D, also potently stimulate phospholipase C-beta in myocardium. PMA stimulation of protein kinase C inactivates phospholipase C and strongly activates phospholipase D and this is probably a major mechanism by which agonists that promote phosphatidyl-4,5-bisphosphate hydrolysis secondary activate phosphatidylcholine-hydrolysis. On the other hand, one group has postulated that formation of phosphatidic acid secondary activates phosphatidyl-4,5-bisphosphate hydrolysis in cardiomyocytes. Whether GTP-binding proteins directly control phospholipase D is not clearly established in myocardium. Phospholipase D activation may also be mediated by an increase in cytosolic free Ca2+ or by tyrosine-phosphorylation.
Mol Cell Biochem
PMID:Regulation and functional significance of phospholipase D in myocardium. 873 27

Transphosphatidylation activity is a characteristic and remarkable property of phospholipase D (PLD) and has been studied in plants and mammalian tissues. This reaction is often used to confirm the properties and/or abnormalities of PLD activity. The mechanism for activating PLD transphosphatidylation seems multiple. Although significant changes of transphosphatidylation activity have been found in some pathological animal models, the biological significance of PLD transphosphatidylation remains largely unknown.
Mol Cell Biochem
PMID:The transphosphatidylation activity of phospholipase D. 873 34

In this report, effects of alpha 1-adrenergic stimulation on phosphatidylcholine (PC) hydrolysis and the subsequent generation of water-soluble choline metabolites were investigated after preincubation of isolated cardiac myocytes of adult rats with [methyl-3H]choline. Choline uptake into cardiac myocytes was apparently mediated by a choline carrier which could be inhibited by hemicholinium-3. Analysis of the intracellular choline metabolites was performed by HPLC. Adrenergic stimulation of cardiac myocytes by (-)-phenylephrine, which is also known to activate the phosphoinositide signaling system, induced the generation of betaine as a selective signal transduction response. Agonist-induced generation of betaine in cardiac myocytes was maximal at 10 min after stimulation, and was optimal at physiologically relevant (-)-phenylephrine concentrations (1-10 microM). Betaine accumulation was transient, and no betaine remained detectable after 15 min. CDP-choline, however, was still elevated after 15 min which is indicative of continued PC resynthesis after adrenergic stimulation. The source of betaine in cellular signalling appeared to be hydrolysis of membrane PC to phosphatidic acid and choline by phospholipase D with subsequent oxidation of choline to betaine. This is based on the observation that radioactivity in unstimulated cells is present only in the lipid phase (presumably as PC) or as phosphocholine in the aqueous phase of the cells. The latter finding suggests that choline is rapidly phosphorylated after uptake into cardiac myocytes. Collectively, these results suggest a hypothetical role of betaine in the cellular signal transduction response to alpha 1-adrenergic stimulation in cardiac myocytes.
J Mol Cell Cardiol 1996 May
PMID:Betaine generation in cardiac myocytes after adrenergic activation of phosphatidylcholine hydrolysis. 876 47

Myocardial phospholipase D (PLD) is located in different subcellular membranes, including sarcolemma (SL) and sarcoplasmic reticulum (SR). In this study, the kinetics of PLD-dependent hydrolytic and transphosphatidylation activities were examined in SL and SR fractions isolated from rat heart by measuring the formation of phosphatidic acid and phosphatidylethanol, respectively. The results showed that, compared to SR PLD, SL PLD had a higher Vmax, i.e. 373 vs. 70 nmol/mg protein/h for the hydrolytic activity and 415 vs. 60 nmol/mg protein/h for the transphosphatidylation activity. In comparison with the SR enzyme, SL PLD had a lower Km value for the hydrolytic activity (0.46 vs. 0.65 mM), buy a higher Km for the transphosphatidylation activity (225 vs. 179 mM). These distinctive kinetic parameters suggest that SL PLD and SR PLD may be isoforms of the enzyme and/or have different membrane domain. Therefore, SL- and SR-localized PLD activities may be under independent control mechanism(s) and play distinct roles in normal conditions and pathological processes.
Mol Cell Biochem
PMID:Kinetics of myocardial phospholipase D. 890 59

The steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] activates in chick myoblasts the breakdown of phosphoinositides by phospholipase C and the hydrolysis of phosphatidylcholine by phospholipase D. Extracellular Ca2+ requirement and GTP-binding protein mediation of 1,25(OH)2D3-dependent activation of phospholipases C and D were investigated in cells prelabelled with [3H]glycerol or [3H]arachidonic acid. Generation of diacylglycerol by phospholipase C and phosphatidylethanol by phospholipase D were shown to be dependent on extracellular calcium, since both responses were suppressed by EGTA and the Ca(2+)-channel blockers nifedipine and verapamil, and were mimicked by the calcium ionophore A23187. The G-protein activators guanosine 5'-O-(3-thiotriphosphate) and AlF4- strongly enhanced diacylglycerol and phosphatidylethanol release in myoblasts while guanosine 5'-O-(2-thiodiphosphate), which inhibits G-protein-mediated signals, abolished 1,25(OH)2D3-dependent diacylglycerol and phosphatidylethanol release. Bordetella pertussis toxin pretreatment suppressed the hormone action. These results suggest that 1,25(OH)2D3-stimulation of phosphoinositide-specific phospholipase C and phospholipase D in chick myoblasts is mediated by a pertussis-sensitive GTP-binding protein(s) and the influx of extracellular calcium.
Mol Cell Endocrinol 1996 Sep 18
PMID:1,25(OH)2-vitamin D3 stimulation of phospholipases C and D in muscle cells involves extracellular calcium and a pertussis-sensitive G protein. 890 51


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