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At least 595 records · Page 33Linked to original sources
PubMed1981

Phase transitions in lipid bilayers. A theoretical model for phosphatidylethanolamine and phosphatidic acid bilayers.

We present an application of an earlier model to the description of phase transitions in phosphatidylethanolamine and phosphatidic acid bilayers. For the former system we modify the model to allow for very slightly closer chain packing. This small modification alone is sufficient to shift the main phase transition temperature to higher values, and to eliminate the lower transition. For the charged bilayers we incorporate electrostatic contributions into the free energy using double layer theory and we consider the excluded volume of counterions at the bilayer/water interface. Phase transition temperatures and the presence of absence of a lower transition are determined for various pH values, and the results are compared with experiment.

Hydrogen-Ion Concentration↗
PubMed1983

Effect of the lipid phase transition on the kinetics of H+/OH- diffusion across phosphatidic acid bilayers.

The kinetics of H+/OH- diffusion across dimyristoyl phosphatidic acid bilayer membranes was measured by following the absorbance of the pH-sensitive indicator Cresol red (o-cresolsulfonphthalein) entrapped in single lamellar vesicles after rapidly changing the external pH in a stopped-flow apparatus. The H+/OH- permeability coefficient was found to be in the 10(-5) to 10(-3) cm . s-1 range. The lipid phase transition has a strong influence on the permeation kinetics as the permeability coefficients in the liquid-crystalline phase are drastically higher. The permeability shows no maximum at the phase transition temperature as is the case for other ions, but displays a similar temperature dependence as water permeation. This is also reflected in the high activation energy of approx. 20 kcal/mol and supports the hypothesis (Nichols, J.W. and Deamer, D.W. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2038-2042) of H+/OH- permeation via hydrogen bonded water molecules. A second slower kinetic phase is also observed, where the permeation is obviously controlled by counterion diffusion. The temperature dependence of this slow process displays the for ion diffusion characteristic maximum in the permeability at the phase-transition temperature.

Diffusion↗
PubMed1984

Structure of divalent cation-phosphatidic acid complexes as determined by 31P-NMR.

A comparative study of the structure of various phosphatidic acid-divalent cation complexes has been completed using 31P solids NMR methods. These complexes had been implicated as important intermediates in the fusion of phospholipid vesicles and several pieces of evidence had suggested that differences in activity of various ions may stem from structural differences among the complexes. Solids NMR studies using spin one-half nuclei reflect structural properties of molecules through partial averaging of chemical shift tensors. We have found significant differences in the chemical shift tensors observed for Mg, Ca and Cd complexes. Low angle X-ray scattering data were used to assure comparison of similar phases. At low temperatures Ca and Cd complexes exhibit unique phases prohibiting comparison with Mg complexes. At higher temperatures, all complexes exhibit a hexagonal phase, and 31P tensors of the complexes in the hexagonal phase can be interpreted using headgroup geometries similar to those found in crystal structures of phospholipids and assuming motional averaging by simple axial motions. Tensors of Ca and Cd complexes are very similar to one another but are significantly broader than those observed for Mg complexes suggesting a more erect headgroup structure. The differences parallel the fusion activities of the ions for which Ca and Cd are similar and significantly enhanced over that of Mg, supporting a structural link to fusion activity.

Cadmium↗
PubMed1986

Changes in membrane polypeptides, polyphosphoinositides and phosphatidate in dense fractions of sickle cells.

When sickle erythrocytes were fractionated on discontinuous isotonic stractan gradients the denser fractions, which were rich in irreversibly sickled cells contained less polyphosphoinositides and more phosphatidate than either lighter sickle cell fractions or normal cells. These changes could be due to activation of a polyphosphoinositide phosphodiesterase in the denser cells. Membrane polypeptide analysis of the denser fractions also showed a marked depletion of band 4.1 and a protein of molecular mass about 110 kDa but an increased amount of a 180 kDa polypeptide which might be a breakdown product of ankyrin. These biochemical alterations could be consequences of Ca2+ accumulation in the denser sickle cells and may contribute to the structural alterations which give rise to irreversibly sickled cells.

Anemia, Sickle Cell↗
PubMed1988

The effect of polyphosphoinositides and phosphatidic acid on the phosphatidylinositol transfer protein from bovine brain: a kinetic study.

The phosphatidylinositol transfer protein from bovine brain (PI-TP) has lipid transfer characteristics which make it well suited to maintain phosphatidylinositol (PI) levels in intracellular membranes (Van Paridon, P.A., Gadella, Jr., T.W.J., Somerharju, P.J. and Wirtz, K.W.A. (1987) Biochim. Biophys. Acta 903, 68-77). Using a continuous fluorimetric transfer assay we have investigated in what way phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) affect the transfer activity of this protein in model systems. The effects were analysed by application of a kinetic model which yielded the association constant (K) and dissociation rate constant (k-) for the PI-TP/vesicle complex. Incorporation of PA, PIP and PIP2 into the phosphatidylcholine-containing vesicles increased the association constant solely by diminishing the dissociation rate constant. This effect could be completely accounted for by changes in the membrane surface charge density. In contrast to the inhibitory effect of PA, the inhibition caused by PIP2 was completely abolished by the addition of neomycin, in agreement with the observed preferential binding of this polyamine antibiotic to PIP2. A rise in pH from 5.5 to 8 drastically reduced the association constant for vesicles containing 16 mol% PA (e.g., from 38 to 2 mM-1), without affecting the Vmax. This effect could be mainly attributed to an increase in the negative charge on PI-TP (isoelectric point 5.5), resulting in an enhanced repulsion. Increasing the negative membrane surface charge at pH 7.4 had the opposite effect. This is interpreted to indicate that the membrane interaction site on PI-TP must be positively charged, overcoming the repulsive forces between PI-TP and the vesicle. Addition of PIP2 micelles as a third component in the transfer assay strongly inhibited PI-TP transfer activity. The extent of inhibition suggests a very high affinity of PI-TP for this lipid.

Animals↗
PubMed1990

Lanthanide(III)-phosphatidic acid complexes: binding site heterogeneity and phase separation.

The luminescent lanthanides are potentially useful probes of cation-induced events involving phospholipid membranes. In this work, the spectroscopic properties of Tb3+, Ce3+ and Eu3+ are shown to be complementary in defining three forms of complex with phosphatidic acid vesicles. Ce3+, in particular, is useful for studying dilute cation-lipid complexes because it has strong excitation bands in the near ultraviolet. In addition to providing a means for detecting chemically distinct forms of lanthanide-lipid complexes, the luminescence can be used to monitor cation-induced lateral segregation. Ce3+ to Tb3+ energy transfer was observed at lanthanide levels as low as 1:1000 Ln3+/phosphatidic acid, indicating clustering or phase separation. Initial clustering occurs on a subsecond timescale, followed by a much slower aggregation continuing for several minutes to hours. Addition of a chelator results in slow release of the lanthanides. In the case of the dioleoylphosphatidic acid complexes, release is bimodal and indicative of cation entrapment; dimyristoylphosphatidic acid complexes exhibit this behavior only at high temperatures. These observations are consistent with the relative tendencies of these two lipids to form the HII phase. This work sets the foundation for experiments designed to determine the size of nucleation sites for cation-induced events such as intramembrane inverted micelle formation and membrane fusion.

Cerium↗
PubMed1991

Asymmetric distribution of phosphoinositides and phosphatidic acid in the human erythrocyte membrane.

The distribution of phosphoinositides and phosphatidic acid (PA) between the outer and inner layers of the human erythrocyte membrane was investigated by using two complementary methodologies: hydrolysis by phospholipase A2 (PLA2) and immunofluorescence detection with monoclonal antibodies against polyphosphoinositides. The contents of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) and PA were decreased by 15-20% after 60 min incubation with PLA2, while that of phosphatidylinositol (PI) was increased. Studies with 32P-labelled cells revealed that PLA2 treatment led to indirect effects on the metabolism of these phospholipids. Therefore, the asymmetric distribution of phosphoinositides and PA was inferred from the data obtained in ATP-depleted erythrocytes. In these cells with arrested phosphoinositide metabolism, the asymmetric distribution of the major phospholipids was maintained: PLA2 hydrolyzed approx. 20% of PI, PIP2 and PA (but no PIP) indicating their localization in the outer layer of the membrane. This finding was confirmed by immunofluorescence studies with antibodies specific to each phosphoinositide. External addition of anti-PIP2 but not anti-PIP gave a positive reaction both in control and in ATP-depleted erythrocytes. A pretreatment of cells with PLA2 led to a decrease in the intensity of anti-PIP2 staining. These results demonstrate that significant fractions of PIP2, PI and PA are localized on the outer surface of the erythrocyte membrane.

Adenosine Triphosphate↗
PubMed1994

Effect of vesicle composition and curvature on the dissociation of phosphatidic acid in small unilamellar vesicles--a 31P-NMR study.

Sonicated small unilamellar vesicles (SUVs) containing phosphatidic acid (PA) give two PA 31P-NMR resonances corresponding to PA molecules in the inner and outer leaflets of the bilayer. This NMR differentiation between the two monolayers is not due to a pH gradient across the membrane but instead reflects differential packing in the inner and outer leaflets imposed by the highly curved SUV surface. The apparent pKa of the outer-leaflet PA increases with decreasing surface curvature and with increasing PA content. The estimated relationship between the apparent pKa of the outer-leaflet PA headgroup and vesicle curvature may provide a qualitative probe for effects related to surface curvature in these model-membrane systems.

Hydrogen-Ion Concentration↗
PubMed1981

Propranolol increases the biosynthesis of phosphatidic acid, phosphatidylinositol and phosphatidylserine in the toad retina. Studies in the entire and subcellular fractions.

1. Intact toad retinas incubated for short periods of time with [2-3H]glycerol were subject to subcellular fractionation. 2. The composition and labeling of glycerolipids were studied in the following subcellular fractions: rod outer segments (ROS), nuclear-photoreceptor inner segment synaptic body (P1), synaptosomal-mitochondrial (P2), microsomal and cytosolic. 3. It was concluded that the biosynthetic de novo route was followed by [2-3H]glycerol in the toad retina since radioactive was located solely in the glycerol backbone of lipids and phosphatidic acid specific activity was the highest. 4. Propranolol produces an increase in the biosynthesis of acidic phospholipids and inhibition in the biosynthesis of zwitterionic lipids in the entire toad retina. The effect was mainly located in microsomes and in the soluble fraction during the first minutes of incubation, being spread afterwards to other fractions. 5. These data are consistent with the view that enzymes of the biosynthesis of glycerolipids are modified in the retinal endoplasmic reticulum by propranolol, providing a useful tool to evaluate the regulation of the pathway.

Animals↗
PubMed1989

Species pattern of phosphatidic acid, diacylglycerol, CDP-diacylglycerol and phosphatidylglycerol synthesized de novo in rat liver mitochondria.

Rat liver mitochondria were incubated with [3H]glycerol 3-phosphate, ATP, CTP and coenzyme A allowing acylatin of glycerophosphate with endogenous fatty acids and the further conversion of labelled phosphatidic acid (PA) to diacylglycerol (DG), CDP-diacylglycerol (CDP-DG) and phosphatidylglycerol (PG). In these glycerolipids, the distribution of label among the individual molecular species was found to be similar, with 16:0-18:1, 16:0-18:2 and 18:0-18:2/16:0-16:0 being the main species. It was concluded that mitochondrial enzymes involved in the de novo synthesis of these glycerolipids exhibited no acyl selectivity for their substrates. The pattern of molecular species of mitochondrial PA, DG and CDP-DG closely approached that of the same glycerolipids synthesized de novo in isolated rat liver microsomes.

Animals↗
PubMed1992

Bis(monoacylglycero)phosphate from PC12 cells, a phospholipid that can comigrate with phosphatidic acid: molecular species analysis by fast atom bombardment mass spectrometry.

Phospholipids from pheochromocytoma (PC12) cells were purified by one-dimensional thin-layer chromatography (TLC). Material corresponding in RF to phosphatidic acid (PA) was analyzed by fast atom bombardment mass spectrometry (FAB). The molecular ions of the major constituents corresponded in mass to phosphatidylglycerols (PG), which, however, have a lower RF value. Analysis of the mass spectra demonstrated that this material consists of bis(monoacylglycero)phosphates (BMP, lysobisphosphatidic acid), a structural isomers of PG. Linked scans of individual molecular ions indicate that BMP from PC12 cells is esterified almost exclusively with monounsaturated (16:1 and 18:1) and polyunsaturated (20:4 and 22:6) fatty acids. One of the two major molecular species contains two monounsaturated (18:1/18:1), while the other contains both a monounsaturated (18:1) and a polyunsaturated (22:6) fatty acid ester. FAB in combination with TLC is ideally suited for analysis of molecular species of phospholipids.

Animals↗
PubMed1992

Phosphatidic acid and polyphosphoinositide metabolism in rod outer segments. Differential role of soluble and peripheral proteins.

The phosphorylation of endogenous diacylglycerol (DAG) and phosphoinositides by [tau-32P]ATP was studied in bovine rod outer segments (ROS) selectively depleted of soluble or peripheral and soluble proteins by treatment with moderate (100 mM) or low (5 mM) ionic strength medium, respectively. DAG kinase activity was similar in bleached and non-bleached ROS extracted with 100 mM medium, and amounted to 70% of that observed in the corresponding non-extracted ROS. Phosphatidic acid (PtdH) labelling in ROS extracted in the dark with low ionic strength medium was markedly lower than in those extracted in light. Thus, even when a major proportion of DAG kinase was associated to the membrane, a soluble form also occurred. Most of the membrane-bound fraction behaved as a peripherally associated protein, its binding to the membrane being modified by light. Ir ROS extracted at moderate ionic strength the labelling of inositides was similar to that in non-extracted ROS. A marked enhancement in polyphosphoinositide labelling was observed in ROS extracted in the dark with low ionic strength. Alkaline treatment of ROS also produced inhibition of polyphosphoinositide phosphorylation. A peripheral form of a type C phospholipase, or a peripheral protein-mediated activation of a particulate form thereof, is suggested. Labelled polyphosphoinositides were more actively hydrolyzed in the light and in the dark plus GTP tau S than in the dark-incubated membranes. The results of phosphorylation experiments in membranes where differential extraction of the alpha subunit of transducin was carried out suggest that alpha and beta tau subunits may play opposite modulating roles in PtdH and polyphosphoinositide metabolism.

Animals↗
PubMed1993

Cholesterol feeding induces hypertriglyceridaemia in hamsters and increases the activity of the Mg(2+)-dependent phosphatidate phosphohydrolase in the liver.

(1) Feeding increased cholesterol to hamsters resulted in a dose-dependent increase in cholesterol and triacylglycerol in very-low-density lipoprotein (VLDL), in serum non-esterified fatty acids and in the activity of the Mg(2+)-dependent phosphatidate phosphohydrolase in liver. (2) The effects of increasing dietary cholesterol by 0.12% (w/w) in addition to feeding fat (14%, w/w) were dependent upon the nature of the fat. Lard in the presence of 0.12% (w/w) cholesterol increased serum triacylglycerols as did olive oil. By contrast, sunflower oil did not cause a significant change in serum triacylglycerol concentrations. (3) There was a highly positive correlation between VLDL triacylglycerol and VLDL cholesterol concentrations suggesting that, at least in this model, there is a close relationship between hypertriglyceridaemia and hypercholesterolaemia.

Animals↗
PubMed1994

Studies on rat liver phosphatidate phosphohydrolase and plasma lipids: effect of HMG-CoA reductase inhibitors.

Normolipidemic rats were treated with HMG-CoA reductase inhibitors (lovastatin or pravastatin) for periods of 1-3 days. Administration of these drugs reduced plasma triacylglycerol levels. Lovastatin-treated rats displayed a 30% lower hepatic triacylglycerol secretion rate compared to controls as estimated using Triton WR-1339. Lovastatin in a dose of 0.1% in the diet for 3 days increased hepatic phosphatidate phosphohydrolase (PAP) activity 2- to 3-fold, both in the cytosolic and microsomal fractions. Similar effects were seen in the presence of 0.2% pravastatin. PAP in both fractions was stimulated to a lesser extent by treatment with 0.1% pravastatin. These differences in PAP activity obtained by different treatment regimens were preserved during purification of cytosolic PAP on hydroxylapatite. The increase in PAP activity upon treatment with lovastatin or pravastatin was gradual and occurred simultaneously with the apparent increase in HMG-CoA reductase activity. In rats treated with the reductase inhibitors, the activity of microsomal and cytosolic PAP was inversely correlated to plasma triacylglycerol levels. The results indicate that hepatic triacylglycerol and cholesterol synthesis might be co-ordinately regulated, and also suggest that the activity of PAP is rapidly modulated in concert with changes in plasma triacylglycerol levels.

Animals↗
PubMed1995

Reversible inhibition by ethanol of Mg(2+)-dependent phosphatidate phosphohydrolase: an in vitro study in the rat reticulocyte.

By using a tracer method, we demonstrate that short-term in vitro exposure of intact rat reticulocytes to ethanol elicits a biphasic response of cell-bound Mg(2+)-dependent phosphatidate phosphohydrolase (PAP). An initial concentration-dependent (200-750 mM) activity decrease is rapidly (< 10 min) followed by reversal of the inhibition in the presence of ethanol, suggesting the development of a cell resistance to the inhibitory agent. Addition to the cell suspension of propranolol (100 microM), a known PAP inhibitor, does elicit PAP inhibition but unlike ethanol, inhibition is not followed by a return with time to control value. Ethanol-induced inhibition of cell-bound PAP was also demonstrated in cell-free extracts, where the Mg(2+)-dependent activity was decreased both in the particulate and soluble fractions. In the intact cells, the transient PAP inhibition occurs in concomitance with an overall increase in total glycerolipid biosynthesis, which is constant over 60-min incubation. We suggest that the biphasic mode of response to ethanol of Mg(2+)-dependent PAP activity may play a role in the mechanism of membrane adaptation to ethanol, and thereby to the pathogenesis of alcoholism.

Adaptation, Physiological↗
PubMed1983

Polymorphic phase preferences of phosphatidic acid: A 31P and 2H NMR study.

31P NMR, 2H NMR and freeze fracture techniques have been employed to investigate the structural preferences of dioleoyl phosphatidic acid (DOPA) under various conditions of pH and divalent cation content. It is shown that DOPA increasingly prefers the HII organization below pH 5, and that low levels of Ca2+ and Mg2+ (Me2+/DOPA = 0.5) induce HII phase structure for pH less than 6.0. Higher Mg2+ and Ca2+ levels (Me2+/DOPA greater than 1.0) induce more complex structures at pH greater than 5.0 which may correspond to intermediates between lamellar and HII organization. This work illustrates the utility of 2H NMR techniques in conjunction with suitable 2H labelled lipids to provide structural information on lipid-water systems, and suggests that 31P NMR techniques for determinations of lipid organization can be applied to advantage in PA containing membranes.

Calcium↗
PubMed1983

Stimulation by prostaglandin F2 alpha of phosphatidic acid-phosphatidylinositol turnover in rat luteal cells.

Prostaglandin F2 alpha (PGF 2 alpha) causes a rapid and marked increase of [32P]-orthophosphate incorporation into phosphatidylinositol (PI) and phosphatidic acid (PA) in rat luteal cells in culture. The incorporation of radioactivity is increased as early as 2 and 5 min after PGF 2 alpha addition into PA and PI, respectively, and by 10 min has reached a 2-fold stimulation over control in both lipid moieties. The labeling of other phospholipids is not affected. PGF 2 alpha exerts its stimulatory effect at an ED50 value of approximately 200 and 60 nM on PI and PA labeling, respectively. By contrast, human chorionic gonadotropin has no effect alone and does not interfere with the PGF 2 alpha-induced stimulation of PA-PI labeling. The striking similarity between the effects of PGF 2 alpha and LHRH on PA-PI labeling suggests that the two agents may exert their direct action on the corpus luteum via a common intracellular mechanism involving acidic phospholipid metabolism.

Animals↗
PubMed1985

Stimulating effect of phosphatidic acid on autophosphorylation of phosphorylase kinase.

Autophosphorylation of phosphorylase kinase from rabbit skeletal muscle was stimulated by acidic phospholipids such as phosphatidic acid (PA), phosphatidylinositol, and phosphatidyl-serine. PA stimulated an initial velocity of autophosphorylation 3.8-fold. When fully autophosphorylated, about 11 mol of phosphate per tetramer (alpha beta gamma delta) were incorporated in the presence of PA and about 6.5 mol in the absence of PA. In the presence of PA (100 micrograms/ml), there was a concomitant enhancement of its kinase activity about 25-fold at pH 6.8. PA (100 micrograms/ml) sharply decreased an apparent Ka for Ca2+ on autophosphorylation from 4.0 X 10(-5) M to 1.0 X 10(-6) M. Available evidence indicates that the Ca2+-activated, PA-dependent autophosphorylation of phosphorylase kinase shows an ability to stimulate glycogen breakdown.

Animals↗