Página 1 dos resultados de 565 itens digitais encontrados em 0.003 segundos

Influence of lysophosphatidylcholine on the C-apolipoprotein content of rat and human triglyceride-rich lipoproteins during triglyceride hydrolysis.

Windler, E E; Preyer, S; Greten, H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1986 EN
Relevância na Pesquisa
27.56%
Remnants produced from rat chylomicrons in hepatectomized rats or from human chylomicrons by incubation in postheparin plasma contained much less C-apolipoproteins, but more lysophosphatidylcholine than the parent chylomicrons. A phospholipid-triglyceride emulsion absorbed C-apolipoproteins during incubation in serum, yet not in postheparin plasma, which led to lipid-hydrolysis and increased in lysophosphatidylcholine. The fraction d = 1.006-1.019 g/ml of human serum comprised more lysophosphatidylcholine and less C-apolipoproteins than the fraction d less than 1.006 g/ml. Injection of heparin induced hydrolysis with an increase in lysophosphatidylcholine and loss of C-apolipoproteins in both fractions. These inverse changes of lysophosphatidylcholine and C-apolipoproteins during lipid-hydrolysis suggest a causal relationship, which is strongly supported by the induction of loss of C-apolipoproteins from rat chylomicrons and human triglyceride-rich lipoproteins by addition of lysophosphatidylcholine in vitro. Apolipoprotein C-II was more affected than C-III. These results may elucidate a mechanism for the regulation of the termination of the triglyceride hydrolysis and the final hepatic uptake of remnants.

Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes.

Nakano, T; Raines, E W; Abraham, J A; Klagsbrun, M; Ross, R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/02/1994 EN
Relevância na Pesquisa
27.68%
Lysophosphatidylcholine is increased in the plasma of hypercholesterolemic patients, is a component of oxidatively modified low-density lipoprotein, and, as such, may play an important role in atherosclerosis. Here we demonstrate that in human monocytes, lysophosphatidylcholine increases the level of mRNA encoding the heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent smooth muscle mitogen. Lysophosphatidylcholine treatment also enhances the release of heparin-binding mitogenic activity by these cells in culture. The anti-inflammatory glucocorticoid dexamethasone inhibits the upregulation of HB-EGF mRNA induced by either lysophosphatidylcholine or bacterial lipopolysaccharide in cultured monocytes. However, the responses induced by lysophosphatidylcholine and by lipopolysaccharide differ in their kinetics. In addition, the response to lysophosphatidylcholine is resistant to the action of cycloheximide, whereas the response to lipopolysaccharide is not, suggesting that the activation mechanisms induced by these two stimuli are different. Since a nuclear run-on assay showed no effect of lysophosphatidylcholine on the transcription of the HB-EGF gene, we speculate that lysophosphatidylcholine may increase the level of HB-EGF mRNA by altering the processing or degradation of primary or mature transcripts. Lysophosphatidylcholine enhancement of monocyte production of HB-EGF may represent an important result of the interactions among oxidized low-density lipoprotein and monocyte-derived macrophages and may play a role in initiation of smooth muscle proliferation in atherogenesis.

Lysophosphatidylcholine Stimulates ATP Dependent Proton Accumulation in Isolated Oat Root Plasma Membrane Vesicles 1

Palmgren, Michael Gjedde; Sommarin, Marianne
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1989 EN
Relevância na Pesquisa
27.14%
Lysophosphatidylcholine at concentrations of 30 micromolar stimulated the rate of MgATP-dependent H+-accumulation in oat (Avena sativa L. cv Rhiannon) root plasma membrane vesicles about 85% while the passive permeability of H+ was unchanged. Activation was dependent on chain length, degree of saturation, and head group of the lysophospholipid. A H+-ATPase assay was developed that allowed the simultaneous measurement of proton pumping and ATPase activity in the same sample. ATP hydrolysis was also stimulated by lysophospholipids and showed the same lipid specificity, but stimulation was only about 25% at 30 micromolar. At higher concentrations of lysophosphatidylcholine the ATPase activity in a latency-free system could be stimulated about 150%. The enzymic properties of proton pumping and ATP hydrolysis were otherwise identical with respect to vanadate sensitivity, Km for ATP and pH optimum. The stimulatory effect of lysophospholipids suggests that these compounds could be part of the regulatory system for plant plasma membrane H+-ATPase activity in vivo.

Chemical mechanism of lysophosphatidylcholine: lysophosphatidylcholine acyltransferase from rabbit lung. pH-dependence of kinetic parameters.

Pérez-Gil, J; Martín, J; Acebal, C; Arche, R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/09/1990 EN
Relevância na Pesquisa
27.61%
Lysophosphatidylcholine: lysophosphatidylcholine acyltransferase is an enzyme that catalyses two reactions: hydrolysis of lysophosphatidylcholine and transacylation between two molecules of lysophosphatidylcholine to give disaturated phosphatidylcholine. Following the kinetic model previously proposed for this enzyme [Martín, Pérez-Gil, Acebal & Arche (1990) Biochem. J. 266, 47-53], the values of essential pK values in free enzyme and substrate-enzyme complexes have now been determined. The chemical mechanism of catalysis was dependent on the deprotonation of a histidine residue with pK about 5.7. This result was supported by the perturbation of pK values by addition of organic solvent. Very high and exothermic enthalpy of ionization was measured, indicating that a conformational re-arrangement in the enzyme accompanies the ionization of the essential histidine residue. These results, as well as the results from previous studies, enabled the proposal of a chemical mechanism for the enzymic reactions catalysed by lysophosphatidylcholine: lysophosphatidylcholine acyltransferase from rabbit lung.

Comparison of albumin-mediated release of lysophosphatidylcholine and lysophosphatidylethanolamine from cultured rat hepatocytes.

Robinson, B S; Baisted, D J; Vance, D E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/11/1989 EN
Relevância na Pesquisa
27.56%
We have investigated the albumin-stimulated release from cultured rat hepatocytes of lysophosphatidylcholine derived from methylation of phosphatidylethanolamine and of lysophosphatidylethanolamine. In the absence [corrected] of albumin, neither lysophosphatidylethanolamine nor lysophosphatidylcholine was released into the culture medium. Albumin stimulated the accumulation of both phospholipids in the medium. After 2 h, 14.1 nmol of lysophosphatidylcholine and 2.0 nmol of lysophosphatidylethanolamine per 3 x 10(6) cells had accumulated in the medium. The rate of release of [3H]ethanolamine-labelled lysophosphatidylethanolamine was rapid in the first 2 h and then was decreased, whereas there was a 1 h lag in the release of [3H]ethanolamine-labelled lysophosphatidylcholine. This apparent lag probably reflected the time necessary for the synthesis of phosphatidylcholine from phosphatidylethanolamine in the cells. Albumin caused a decrease in labelled cellular lysophosphatidylethanolamine and lysophosphatidylcholine which only partially accounted for the accumulation of the labelled phospholipids in the medium. Albumin also stimulated the release of labelled phosphatidylethanolamine (almost 3-fold) and phosphatidylcholine (2-fold) into the medium. There was no detectable change in the labelling of the cellular pools of these phospholipids...

Lysophosphatidylcholine increases the secretion of cholesteryl ester-poor triacylglycerol-rich lipoproteins by CaCo-2 cells.

Field, F J; Born, E; Chen, H; Murthy, S; Mathur, S N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/11/1994 EN
Relevância na Pesquisa
27.56%
To address the effect of lysophosphatidylcholine on triacylglycerol transport in intestine, CaCo-2 cells, grown on semipermeable supports, were incubated with lysophosphatidylcholine solubilized in 1 mM taurocholate. [14C]Palmitoyllysophosphatidylcholine was readily taken up and incorporated predominantly into cellular phospholipids, particularly phosphatidylcholine. Twenty-five percent of the label was found in triacylglycerols. Compared with labelled cellular phospholipids, labelled triacylglycerols were preferentially secreted. Lysophosphatidylcholine caused a profound decrease in cholesteryl ester synthesis and secretion, whereas cellular triacylglycerol mass and triacylglycerol synthesis and secretion were increased. The effect was more pronounced with oleoyllysophosphatidylcholine than with either palmitoyl- or stearyl-lysophosphatidylcholine. Lysophosphatidylcholine increased the secretion of immunoreactive and newly-synthesized apoprotein B (apoB) without altering the rate of apoB synthesis. Thus, luminal lysophosphatidylcholine and/or its uptake decreases cholesterol esterification and secretion, but increases triacylglycerol synthesis and secretion, triacylglycerol mass accumulation and the secretion of apoB by CaCo-2 cells.

Lysophosphatidylcholine metabolism and lipoprotein secretion by cultured rat hepatocytes deficient in choline.

Robinson, B S; Yao, Z M; Baisted, D J; Vance, D E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/05/1989 EN
Relevância na Pesquisa
27.56%
The metabolism of lysophosphatidylcholine was studied in cultured rat hepatocytes deficient in choline and methionine. Even though the cells were defective in phosphatidylcholine biosynthesis, the albumin-stimulated release of lysophosphatidylcholine (1.9 nmol/h per mg of cellular protein) was similar to that in hepatocytes supplemented with choline. Albumin also stimulated (1.4-fold) the release of phosphatidylcholine from the deficient cells. The extra phosphatidylcholine and lysophosphatidylcholine in the medium were largely recovered in the albumin fraction (density greater than 1.18 g/ml), suggesting that albumin released these lipids from hepatocytes because of binding to this protein. The secretion of glycerophosphocholine was decreased by about 40% by the addition of albumin. When choline-deficient hepatocytes were supplemented with lysophosphatidylcholine, it was transported into the cells and mainly acylated to form phosphatidylcholine, which increased in mass by 30-35% in the first 4 h of incubation. Lysophosphatidylcholine was shown to be as effective as choline in restoring the secretion of very-low-density lipoproteins to normal amounts, as judged by the secretion of triacylglycerol, phosphatidylcholine and the apolipoproteins associated with very-low-density lipoproteins. Thus phosphatidylcholine synthesis via reacylation of lysophosphatidylcholine...

Evidence for the reversibility of the acyl-CoA:lysophosphatidylcholine acyltransferase in microsomal preparations from developing safflower (Carthamus tinctorius L.) cotyledons and rat liver.

Stymne, S; Stobart, A K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/10/1984 EN
Relevância na Pesquisa
27.5%
Acyl exchange between acyl-CoA and position 2 of sn-phosphatidylcholine occurs in the microsomal preparations of developing safflower cotyledons. Evidence is presented to show that the acyl exchange is catalysed by the combined back and forward reactions of an acyl-CoA:lysophosphatidylcholine acyltransferase (EC 2.3.1.23). The back reaction of the enzyme was demonstrated by the stimulation of the acyl exchange with free CoA and by the observation that the added CoA was acylated with acyl groups from position 2 of sn-phosphatidylcholine. Re-acylation of the, endogenously produced, lysophosphatidylcholine with added acyl-CoA occurred with the same specificity as that observed with added palmitoyl lysophosphatidylcholine. A similar acyl exchange, catalysed by an acyl-CoA:lysophosphatidylcholine acyltransferase, occurred in microsomal preparations of rat liver. The enzyme from safflower had a high specificity for oleate and linoleate, whereas arachidonate was the preferred acyl group in the rat liver microsomal preparations. The rate of the back reaction was 3-5% and 0.2-0.4% of the forward reaction in the microsomal preparations of safflower and rat liver respectively. Previous observations, that the acyl exchange in safflower microsomal preparations was stimulated by bovine serum albumin and sn-glycerol 3-phosphate...

Fatty acid specificity for the synthesis of triacylglycerol and phosphatidylcholine and for the secretion of very-low-density lipoproteins and lysophosphatidylcholine by cultures of rat hepatocytes.

Graham, A; Zammit, V A; Brindley, D N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/02/1988 EN
Relevância na Pesquisa
27.31%
1. The synthesis and secretion of glycerolipids by monolayer cultures of rat hepatocytes was measured by using radioactive choline, glycerol and fatty acids and by measuring the concentration of triacylglycerols in the cells. 2. The incorporation of glycerol into triacylglycerol and the accumulation of this lipid in hepatocytes showed little specificity for fatty acids, except for eicosapentaenoate, which stimulated least. Oleate was more effective at stimulating triacylglycerol secretion than were palmitate, stearate, arachidonate and eicosapentaenoate. 3. Linoleate, linolenate, arachidonate and eicosapentaenoate stimulated the incorporation of glycerol and choline into phosphatidylcholine that was secreted into the medium. By contrast, palmitate and stearate produced relatively high incorporations into the phosphatidylcholine that remained in the cells. 4. The incorporation of glycerol and choline into lysophosphatidylcholine in the medium was stimulated 2-3-fold by all of the unsaturated fatty acids tested, whereas palmitate and stearate failed to stimulate if the acids were added separately. When 1 mM-stearate was added with 1 mM-linoleate, the incorporation of linoleate into lysophosphatidylcholine was about 4 times higher than that of stearate. 5. It is proposed that the secretion of lysophosphatidylcholine by the liver could provide a transport system for choline and essential unsaturated fatty acids to other organs.

Factors regulating the secretion of lysophosphatidylcholine by rat hepatocytes compared with the synthesis and secretion of phosphatidylcholine and triacylglycerol. Effects of albumin, cycloheximide, verapamil, EGTA and chlorpromazine.

Graham, A; Bennett, A J; McLean, A A; Zammit, V A; Brindley, D N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/08/1988 EN
Relevância na Pesquisa
27.31%
1. The synthesis and secretion of glycerolipid by monolayer cultures of rat hepatocytes was measured by determining the incorporations of [3H]glycerol, [3H]oleate and [14C]choline and by the absolute concentration of triacylglycerol. 2. The presence of albumin in the medium stimulated the accumulation of lysophosphatidylcholine in the medium by 11-13-fold. 3. Cycloheximide did not significantly alter the accumulation of lysophosphatidylcholine. 4. This process was particularly sensitive to inhibition by chlorpromazine and verapamil, compared with the secretion of triacylglycerol and phosphatidylcholine. By contrast, it was relatively less sensitive to EGTA. 5. It is suggested that intracellular Ca2+ may be important in the production of lysophosphatidylcholine, which then accumulates in the medium by binding to albumin. In vivo this lysophosphatidycholine may be a means of delivering choline and polyunsaturated fatty acids to other organs.

Albumin stimulates the release of lysophosphatidylcholine from cultured rat hepatocytes.

Baisted, D J; Robinson, B S; Vance, D E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/08/1988 EN
Relevância na Pesquisa
27.71%
The effect of albumin on the release of [3H]lysophosphatidylcholine from cultured rat hepatocytes prelabelled with [Me-3H]choline was studied. In the absence of serum and albumin from the medium, the cells released essentially no [3H]lysophosphatidylcholine. Albumin stimulated this process dramatically, and it reached a plateau at 2 mg/ml. After an initial lag of 30 min, the release of [3H]lysophosphatidylcholine was linear for at least 4 h. At low concentrations, albumin slightly stimulated [3H]phosphatidylcholine release. The albumin had no measurable effect on the metabolism of cellular [3H]phosphatidylcholine, [3H]lysophosphatidylcholine or [3H]glycerophosphocholine. In addition, albumin did not alter the release of 3H-labelled water-soluble compounds, including [3H]glycerophosphocholine, into the medium. The possibility that the [3H]lysophosphatidylcholine was arising from catabolism of [3H]phosphatidylcholine in the medium by secreted enzymes was excluded. The effect on [3H]lysophosphatidylcholine secretion was also observed when the cells were incubated with alpha-cyclodextrin, a cyclic polysaccharide that has the ability to bind lysophosphatidylcholine. The albumin-released lysophosphatidylcholine was enriched in unsaturated fatty acids. Alteration of the fatty acid composition of cellular phosphatidylcholine gave rise to parallel changes in phosphatidylcholine and lysophosphatidylcholine in the medium. It is concluded that phosphatidylcholine is constantly being degraded in the rat hepatocyte to lysophosphatidylcholine which is released into the medium only when a suitable acceptor is present.

Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes.

Mangiapane, E H; Brindley, D N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/01/1986 EN
Relevância na Pesquisa
27.31%
Rat hepatocytes in monolayer culture were preincubated for 19 h with 1 microM-dexamethasone, and the incubation was continued for a further 23 h with [14C]oleate, [3H]glycerol and 1 microM-dexamethasone. Dexamethasone increased the secretion of triacylglycerol into the medium in particles that had the properties of very-low-density lipoproteins. The increased secretion was matched by a decrease in the triacylglycerol and phosphatidylcholine that remained in the hepatocytes. Preincubating the hepatocytes for the total 42 h period with 36 nM-insulin decreased the amount of triacylglycerol in the medium and in the cells after the final incubation for 23 h with radioactive substrates. However, insulin had no significant effect on the triacylglycerol content of the cell and medium when it was present only in the final 23 h incubation. Insulin antagonized the effects of dexamethasone in stimulating the secretion of triacylglycerol from the hepatocytes, especially when it was present throughout the total 42 h period. The labelling of lysophosphatidylcholine in the medium when hepatocytes were incubated with [14C]oleate and [3H]glycerol was greater than that of phosphatidylcholine. The appearance of this lipid in the medium, unlike that of triacylglycerol and phosphatidylcholine...

The presence of lysophosphatidylcholine in chromaffin granules

Arthur, Gilbert; Sheltawy, Ayman
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/11/1980 EN
Relevância na Pesquisa
27.68%
Lysophosphatidylcholine is thought to be a characteristic component of the chromaffin granules in adrenal glands. By the use of a t.l.c. system that resolves minor phospholipids satisfactorily, this subcellular location was confirmed in the present study in bovine glands. However, phospholipid degradation was demonstrated in homogenates of the adrenal medulla and cortex under conditions similar to those of subcellular fractionation (incubation at 4°C for 90min). Phosphatidylethanolamine and cardiolipin were hydrolysed, but the concentration of lysophosphatidylcholine did not change, indicating that the latter was present in the medulla before this treatment. Attempts were made to decrease the time between death of the animal and the extraction of lipids. Lysophosphatidylcholine was easily demonstrable in lipid extracts of the dissected medulla and even in those of the whole bovine gland. For practical reasons it is not possible to decrease further the time lapse before extraction in the case of this animal. Adrenal glands were obtained from anaesthetized and untreated rabbits. These were frozen immediately in liquid N2 and the lipids were extracted. In a control experiment, the glands from rabbit were dissected and treated in the same manner as with those of ox...

Stimulation of collagen galactosyltransferase and glucosyltransferase activities by lysophosphatidylcholine.

Anttinen, H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/10/1976 EN
Relevância na Pesquisa
27.56%
Lysophosphatidylcholine stimulated the activities of collagen galactosyl- and glucosyl-transferases in chick-embryo extract and its particulate fractions in vitro, whereas essentially no stimulation was noted in the high-speed supernatant, where the enzymes are soluble and membrane-free. The stimulatory effect of lysophosphatidylcholine was masked by 0.1% Triton X-100. In kinetic experiments lysophosphatidylcholine raised the maximum velocities with respect to the substrates and co-substrates, whereas no changes were observed in the apparant Km values. Phospholipase A preincubation of the chick-embryo extract resulted in stimulation of both transferase activities, probably gy generating lysophosphatides from endogenous phospholipids. No stimulation by lysophosphatidylcholine was found when tested with 500-fold-purified glycosyltransferase. The results suggest that collagen glycosyltransferases must be associated with the membrane structures of the cell in order to be stimulated by lysophosphatidylcholine. Lysophosphatidylcholine could have some regulatory significance in vivo, since its concentration in the cell is comparable with that which produced marked stimulation in vitro.

The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys

Illingworth, D. Roger; Portman, Oscar W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1972 EN
Relevância na Pesquisa
27.61%
1. Adult squirrel monkeys were injected intravenously with doubly labelled lysophosphatidylcholine (a mixture of 1-[1-14C]palmitoyl-sn-glycero-3-phosphorylcholine and 1-acyl-sn-glycero-3-phosphoryl[Me-3H]choline; 3H:14Cratio 3.75) complexed to albumin, and the incorporation into the brain was studied at times up to 3h. 2. After 20min, 1% of the radioactivity injected as lysophosphatidylcholine had been taken up by the brain. 3. Approx. 70% of the doubly labelled lysophosphatidylcholine taken up by both grey and white matter was converted into phosphatidylcholine, whereas about 30% was hydrolysed. 4. The absence of significant radioactivity in the phosphatidylcholine, free fatty acid and water-soluble fractions of plasma up to 30min after injection of doubly labelled lysophosphatidylcholine rules out the possibility that the rapid labelling of these compounds in brain could be due to uptake from or exchange with their counterparts in plasma. 5. The similarity between the 3H:14C ratios of brain phosphatidylcholine and injected lysophosphatidylcholine demonstrates that formation of the former occurred predominantly via direct acylation. 6. Analysis of the water-soluble products from lysophosphatidylcholine catabolism revealed that appreciable glycerophosphoryl-[Me-3H]choline did not accumulate in the brain and that radioactivity was incorporated into choline...

Preparation of [32P]phosphatidylcholine and [32P]lysophosphatidylcholine by using soya beans.

Hubmann, F H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/06/1979 EN
Relevância na Pesquisa
27.14%
This method describes a procedure that can be carried out easily to obtain large amounts of [32P]phosphatidylcholine and [32P]lysophosphatidylcholine. The method involves germinating soya beans in the presence of [32P]Pi. The yield was 0.58% for [P]phosphatidylcholine and 0.52% for [32P]lysophosphatidylcholine, and the specific radioactivity of both was 10(7) d.p.m./mumol.

Inhibition of autotaxin production or activity blocks lysophosphatidylcholine-induced migration of human breast cancer and melanoma cells

Gaetano, Cristoforo G.; Samadi, Nasser; Tomsig, Jose L.; Macdonald, Timothy L.; Lynch, Kevin R.; Brindley, David N.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/2009 EN
Relevância na Pesquisa
27.42%
Increased expression of autotaxin is linked to several malignancies including glioblastoma, breast, renal, ovarian, lung and thyroid cancers. Autotaxin promotes metastasis as well as cell growth, survival, and migration of cancer cells. These actions could depend on the non-catalytic effects of autotaxin on cell adhesion, or the catalytic activity of autotaxin, which converts lysophosphatidylcholine into lysophosphatidate in the extracellular environment. Both lysophosphatidylcholine and lysophosphatidate have been reported to stimulate migration through their respective G-protein coupled receptors. The present study determines the roles of autotaxin, lysophosphatidylcholine and lysophosphatidate in controlling the migration two cancer cell lines MDA-MB-231 breast cancer cells, which produce little autotaxin and MDA-MB-435 melanoma cells that secrete significant levels of autotaxin. Lysophosphatidylcholine alone was unable to stimulate the migration of either cell type unless autotaxin was present. Knocking down autotaxin secretion, or inhibiting its catalytic activity, blocked cell migration by preventing lysophosphatidate production and the subsequent activation of LPA1/3 receptors. We conclude that inhibiting autotaxin production or activity of could provide a beneficial adjuvant to chemotherapy for preventing metastasis in patients with high autotaxin expression in their tumors.

Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function

Hollie, Norris I.; Cash, James G.; Matlib, M. Abdul; Wortman, Matthew; Basford, Joshua E.; Abplanalp, William; Hui, David Y.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.73%
Mice deficient in group 1b phospholipase A2 have decreased plasma lysophosphatidylcholine and increased hepatic oxidation that is inhibited by intraperitoneal lysophosphatidylcholine injection. This study sought to identify a mechanism for lysophosphatidylcholine-mediated inhibition of hepatic oxidative function. Results showed that in vitro incubation of isolated mitochondria with 40-200 μM lysophosphatidylcholine caused cyclosporine A-resistant swelling in a concentration-dependent manner. However, when mitochondria were challenged with 220 μM CaCl2, cyclosporine A protected against permeability transition induced by 40 μM, but not 80 μM lysophosphatidylcholine. Incubation with 40-120 μM lysophosphatidylcholine also increased mitochondrial permeability to 75 μM CaCl2 in a concentration-dependent manner. Interestingly, despite incubation with 80 μM lysophosphatidylcholine, the mitochondrial membrane potential was steady in the presence of succinate, and oxidation rates and respiratory controls indices were similar to controls in the presence of succinate, glutamate/malate, and palmitoyl-carnitine. However, mitochondrial oxidation rates were inhibited by 30-50% at 100 μM lysophosphatidylcholine. Finally, while 40 μM lysophosphatidylcholine has no effect on fatty acid oxidation and mitochondria remained impermeable in intact hepatocytes...

Characterization of the Gene Encoding the Major Secreted Lysophospholipase A of Legionella pneumophila and Its Role in Detoxification of Lysophosphatidylcholine

Flieger, Antje; Neumeister, Birgid; Cianciotto, Nicholas P.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2002 EN
Relevância na Pesquisa
27.31%
We previously showed that Legionella pneumophila secretes, via its type II secretion system, phospholipase A activities that are distinguished by their specificity for certain phospholipids. In this study, we identified and characterized plaA, a gene encoding a phospholipase A that cleaves fatty acids from lysophospholipids. The plaA gene encoded a 309-amino-acid protein (PlaA) which had homology to a group of lipolytic enzymes containing the catalytic signature GDSL. In Escherichia coli, the cloned gene conferred trypsin-resistant hydrolysis of lysophosphatidylcholine and lysophosphatidylglycerol. An L. pneumophila plaA mutant was generated by allelic exchange. Although the mutant grew normally in standard buffered yeast extract broth, its culture supernatants lost greater than 80% of their ability to release fatty acids from lysophosphatidylcholine and lysophosphatidylglycerol, implying that PlaA is the major secreted lysophospholipase A of L. pneumophila. The mutant's reduced lipolytic activity was confirmed by growth on egg yolk agar and thin layer chromatography and was complemented by reintroduction of an intact copy of plaA. Overexpression of plaA completely protected L. pneumophila from the toxic effects of lysophosphatidylcholine...

Theoretical approach to the steady-state kinetics of a bi-substrate acyl-transfer enzyme reaction that follows a hydrolysable-acyl-enzyme-based mechanism. Application to the study of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase from rabbit lung.

Martín, J; Pérez-Gil, J; Acebal, C; Arche, R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/02/1990 EN
Relevância na Pesquisa
27.31%
A kinetic model is proposed for catalysis by an enzyme that has several special characteristics: (i) it catalyses an acyl-transfer bi-substrate reaction between two identical molecules of substrate, (ii) the substrate is an amphiphilic molecule that can be present in two physical forms, namely monomers and micelles, and (iii) the reaction progresses through an acyl-enzyme-based mechanism and the covalent intermediate can react also with water to yield a secondary hydrolytic reaction. The theoretical kinetic equations for both reactions were deduced according to steady-state assumptions and the theoretical plots were predicted. The experimental kinetics of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase from rabbit lung fitted the proposed equations with great accuracy. Also, kinetics of inhibition by products behaved as expected. It was concluded that the competition between two nucleophiles for the covalent acyl-enzyme intermediate, and not a different enzyme action depending on the physical state of the substrate, is responsible for the differences in kinetic pattern for the two activities of the enzyme. This conclusion, together with the fact that the kinetic equation for the transacylation is quadratic, generates a 'hysteretic' pattern that can provide the basis of self-regulatory properties for enzymes to which this model could be applied.