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At least 613 records · Page 34Linked to original sources
PubMed1986

Cationic amphiphilic drugs perturb the metabolism of inosititides and phosphatidic acid in photoreceptor membranes.

Incubation of purified bovine photoreceptor rod outer segments with [gamma-32P]ATP resulted in the labeling of phosphatidylinositol 4-phosphate (PIP) and phosphatidic acid (PA) with little labeling of phosphatidylinositol 4,5-bisphosphate (PIP2). Propranolol inhibited in a dose-dependent manner the labeling of PA and enhanced that of PIP. Various cationic amphiphilic drugs also were tested for these effects. Propranolol had the same effects on high-speed rat brain particulate material. While this particular preparation displayed more labeling of PIP2, propranolol was ineffective, as it was on retinal PIP-kinase. Ca2+-activated polyphosphoinositide phosphodiesterase activity in nerve-ending membranes also was inhibited by propranolol. It is concluded that cationic amphiphilic drugs can inhibit diacylglycerol kinase and the polyphosphoinositide phosphodiesterase and stimulate the phosphatidylinositol-kinase (but not PIP-kinase).

Acetamides↗
PubMed1989

Cytosolic alkalinization alone is not sufficient for Ca2+ mobilization, phosphatidic acid formation, and protein phosphorylation in human platelets.

One of the earliest events following stimulation of human platelets with thrombin is a rise in the cytosolic pH, pHi, mediated by Na+/H+ exchange, and an increase in the cytosolic free Ca2+ concentration, [Ca2+]i. In the present study we investigated whether an increase in pHi alone, induced by the Na+/H+ ionophore monensin, is sufficient for platelet activation. Although monensin (20 microM) raised pHi from 7.10 +/- 0.05 (n = 21) to 7.72 +/- 0.17 (n = 13), neither Ca2+ influx nor mobilization were detectable upon this treatment in fura2-loaded platelets. In contrast, thrombin (0.05 U/ml) raised pHi to 7.31 +/- 0.10 (n = 10) and increased [Ca2+]i by more than 250 nM both in the presence and absence of extracellular Ca2+. Thrombin also caused the formation of phosphatidic acid and phosphorylation of the 20 kDa and 47 kDa proteins in platelets labeled with 32P. Monensin, however, induced none of these responses. It is concluded that an increase in pHi alone is not a sufficient trigger for platelet activation but enhances intracellular signal transduction in platelets stimulated by natural agonists.

Blood Platelets↗
PubMed1989

Mass determination of receptor-mediated accumulation of phosphatidate and diglycerides in human neutrophils measured by Coomassie blue staining and densitometry.

Quantitation of 1,2-diacylglycerol (AAG), 1-0-alkyl-2-acylglycerol (EAG) and phosphatidic acid (PA) was conducted in polymorphonuclear leukocytes (PMN) labeled with 1-0-[3H]alkyl-2-acyl-GPC following stimulation with 1 microM fMLP using Coomassie blue staining and densitometry. At 5s AAG and PA increased by 80% and 107%, respectively, over controls. The accumulation of PA, which reached a maximum by 30s, was higher than AAG by 302% at 5s, and 550% at 30s. EAG accumulation was delayed by 15s following stimulation of PMN. These results show that AAG accumulates before EAG and support the role of AAG in cellular activation, perhaps, via the stimulation of protein kinase C (PKC). EAG may serve to counter the effects of AAG or may itself elicit responses. The high concentrations of PA which accumulate early suggest that PA may be generated by the activation of phospholipase D in PMN stimulated with fMLP.

Chromatography, Thin Layer↗
PubMed1989

Inositol lipids and phosphatidic acid inhibit cell-free activation of neutrophil NADPH oxidase.

The effect of inositol lipids on the SDS-initiated cell-free activation of NADPH oxidase in membranes of human neutrophils was investigated. In a system consisting of low density membranes, cytosol and SDS, low doses of phosphatidylinositol, phosphatidylinositol mono- and biphosphates and phosphatidic acid interfered with activation of the oxidase. The inhibition was relieved by increasing concentrations of the cytosol. Conversely, preincubation of multilamellar phosphoinositide vesicles with cytosol reduced its ability to support activation of the oxidase.

Cardiolipins↗
PubMed1990

Phorbol-12-myristate-13-acetate activation of phospholipase D in human neutrophils leads to the production of phosphatides and diglycerides.

The contribution of phospholipase D (PLD) to the production of phosphatides (PA) and diglycerides (DG) in phorbol-12-myristate-13-acetate (PMA)-stimulated human neutrophils was studied. Neutrophils were double labeled with 1-O-[3H]alkyl-phosphatidylcholine [( 3H]alkyl-PC) and alkyl-[32P]PC. Upon stimulation with PMA, these cells produced 1-O-alkyl-PA (alkyl-PA) and, in the presence of ethanol, 1-O-alkyl-phosphatidylethanol (alkyl-PEt) both containing 3H and 32P. Lagging behind alkyl-PA and alkyl-PEt formation was the production of 1-O-[3H]alkyl-diglyceride [( 3H]alkyl-DG) and [32P]orthophosphate [( 32P]PO4), suggesting dephosphorylation of alkyl-PA by PA phosphohydrolase (PPH). Furthermore, the PPH inhibitor, propranolol, inhibited the formation of both [3H]alkyl-DG and [32P]PO4, while increasing alkyl-PA levels (containing both 3H and 32P). PMA-induced DG mass accumulation was also inhibited by propranolol. The results of this study demonstrate that PMA activates PLD in neutrophils leading to the generation of PA and that the bulk of the DG mass accumulation is derived from the sequential actions of PLD and PPH on PC.

Diglycerides↗
PubMed1987

The effects of hydrazine on the phosphatidate phosphohydrolase activity in rat liver.

Injection of hydrazine (0.7 mmole/kg) in the male fasting rats caused an increase in phosphatidate phosphohydrolase (PAP) activity in the soluble fraction of the liver. The increased PAP activity was parallel with a rise in hepatic triacylglycerol (TG) (3.5-fold) and in the catecholamine concentration (3.4-fold) in adrenal glands. Hydrazine also increased serum glucose. The hydrazine-induced increase in PAP activity and TG accumulation was completely prevented by adrenalectomy. The data suggest that increased PAP activity is at least partly responsible for hydrazine-induced fatty liver and that adrenal hormones may take part in the mechanism by which hydrazine exerts its effects on the liver.

Adrenal Glands↗
PubMed1990

Studies on peroxidation processes of model membranes and synaptosomes: role of phosphatidic acid.

Dipalmitoylphosphatidic acid (DPPA) was found to exert a strong inhibitory effect on Fe-induced peroxidation of arachidonic acid inserted into liposomal dipalmitoylphosphatidylcholine (DPPC) vesicles. This inhibition was quite effective both below and above the phase transition temperature of the liposomes. Moreover, we demonstrated the antiperoxidative activity of phosphatidic acid (PA) in synaptosomal membranes. PA enriched synaptosomes were prepared by the stimulation of the endogenous phospholipase D activity or by the incubation of the synaptosomes with Streptomyces chromofuscus phospholipase D. The possible contribution of PA to the in vivo defense mechanism against free radical-induced damage is discussed.

Animals↗
PubMed1990

Electric field increases the phase transition temperature in the bilayer membrane of phosphatidic acid.

The effect of the electric field on the phase transition temperature (Tc) of acidic 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) and 1,2-dipalmitoyl-sn-glycero-3-thionphosphate (thion-DPPA) and zwitterion, i.e. 1,2-dipalmitoyl-rac-3-phosphocholine and 1,2-distearoyl-rac-glycero-3-phosphocholine (DPPC and DSPC), lipids has been investigated. The phase transition was detected using the jump-like increase effect in the conductance of the planar bilayer membrane. A voltage increase to 150 mV has been shown to increase the phase transition temperature in a bilayer lipid membrane (BLM) of phosphatidic acids (DPPA and thion-DPPA) by 8-12 degrees C while the transition temperature in the bilayer of zwitterion lipids (DPPC and DSPC) increases insignificantly. The increasing of Tt in BLM of acidic lipids is attributed to the voltage-induced changes in the molecule packing density.

Chemical Phenomena↗
PubMed1993

Sphingosine-mediated membrane association of DNA and its reversal by phosphatidic acid.

Resonance energy transfer was measured between egg phosphatidylcholine liposomes containing the intramolecular excimer forming pyrene-labelled phospholipid analogue 1,2-bis[pyren-1-(-yl)]decanoyl-sn-glycero-3-phosphocholine (bisPDPC) as a donor and DNA-bound adriamycin as an acceptor. Membrane association of DNA turned out to be critically dependent on the presence of sphingosine in the liposomes. Identical result was obtained by measuring the extent of quenching of the fluorescent DNA-bound dye Hoechst 33258 due to energy transfer to the lipophilic stain Nile Red incorporated in egg phosphatidylcholine liposomes containing varying amounts of sphingosine. The attachment of DNA to sphingosine-containing membranes could be reversed by the further inclusion of the negatively charged phosphatidic acid up to approximately 1:2 PA/sphingosine molar ratio in the liposomes, thus suggesting the involvement of electrostatic interactions. Differential scanning calorimetry measurements confirmed a lack of association between DNA and dimyristoylphosphatidylcholine liposomes. Instead drastic changes were produced by DNA in the heat capacity scans measured for liposomes also incorporating sphingosine. Fluorescence microscopy revealed an extensive aggregation of sphingosine containing pyrene-phosphatidylcholine-labelled egg phosphatidylcholine liposomes in the presence of DNA. Together with other available data on the effects of sphingosine, the present findings suggest that sphingosine could directly alter the chromatin structure. Accordingly, such alterations may contribute to the control of replication and gene expression.

Bisbenzimidazole↗
PubMed1996

Messenger functions of phosphatidic acid.

Under physiological conditions, phosphatidic acid (PA) is an anionic phospholipid with moderate biological reactivity. Some of its biological effects can be attributed to lyso-PA and diacylglycerol generated by the action of cellular hydrolases. However, it is clear that the parent compound exhibits biological activities of its own. Early studies implicated PA in the transport of Ca++ across plasma membranes as well as in the mobilization of intracellular stored calcium. Both responses may be induced as a consequence of other cellular processes activated by PA, as opposed to being directly mediated by the lipid. PA may be involved in the activation of certain functions confined to specialized groupings of cells, such as the neutrophil superoxide-generating enzyme or actin polymerization. Recent studies implicate PA as an activator of intracellular protein kinases, and a PA-dependent superfamily of kinases involved in cellular signalling has been hypothesized. Deployed on the outer surface of the plasma membrane, PA potentially provides a method of communication between cells in direct contact. This review will explore the known functions of PA as an intracellular mediator and extracellular messenger of biological activities and address ways in which these functions are potentially regulated by cellular enzymes which hydrolyse the phospholipid.

Animals↗
PubMed1982

Effects of eicosatetraynoic acid (ETYA) on cultured pig thyroid cells. Relationships between the inhibition of the phosphatidate-phosphatidyl inositol cycle, the iodination and the cyclic AMP responsiveness to thyrotropin.

The arachidonate inhibition of the adenylate-cyclase system of cultured pig thyroid cells was not mediated by cyclooxygenase, lipoxygenase or peroxidase metabolites. Indeed ETYA, an inhibitor of cyclooxygenase and lipoxygenase, and methimazole, an inhibitor of peroxidase and iodination were without effect on the arachidonate inhibition. Moreover the effect of arachidonate was amplified by a combination with ETYA. In 32P incorporation experiments we observed a modification of the labelling of individual phospholipids of cultured pig thyroid cells resulting in a decrease into phosphatidylinositol (PI) and an increase into phosphatidate (PA) of arachidonate and ETYA-treated cells. These results may be explained by an inhibition of CDP-diacylglycerol: inositol transferase and conversely a stimulation of PI specific phospholipase C yielding a decrease in PI and an increase in PA, which inhibits in turn adenylate cyclase activity possibly by Ca2+ translocation.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Spermine promotes the translocation of phosphatidate phosphohydrolase from the cytosol to the microsomal fraction of rat liver and it enhances the effects of oleate in this respect.

Spermine (0.5-2 mM) promoted the translocation of phosphatidate phosphohydrolase from the soluble to the microsomal fraction in a cell-free system derived from rat liver. By contrast, spermidine (1 mM) and putrescine (1 mM) had no significant effect on the translocation when added alone. Spermine, and to a lesser extent, spermidine, enhanced the translocating action of oleate and increased its effectiveness in transferring the phosphohydrolase from the soluble to the microsomal fraction. It is proposed that the phosphohydrolase becomes metabolically active when it combines with membranes and that polyamines might help to regulate this interaction. This could facilitate the action of fatty acids and enable cells to increase their capacity for triacylglycerol synthesis to match an increased availability of fatty acids.

Animals↗
PubMed1985

Persistent activity modification of phosphatidate phosphohydrolase and fatty acyl-CoA synthetase on incubation of adipocytes with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate.

Incubation of rat adipocytes with the phorbol ester TPA caused a dose-dependent, persistent increase in phosphatidate phosphohydrolase activity and decrease in fatty acyl-CoA synthetase activity. Half-maximal effects were obtained with 1-2 X 10(-10) M TPA. TPA did not alter basal or noradrenaline-stimulated lipolysis. It is suggested that these two enzymes might be modified by protein kinase C.

Adipose Tissue↗
PubMed1985

Vasopressin rapidly stimulates phosphatidic acid-phosphatidylinositol turnover in rat anterior pituitary cells.

In cultured rat anterior pituitary cells, the agonist [Asu1,6, Arg8]vasopressin (AVP-A) increased by 1.5-fold 32Pi incorporation into phosphatidic acid (PA), as early as 15 s after its addition. Increased phosphatidylinositol (PI) labeling became significant 4 min after AVP-A addition. Dose-response measurements with AVP-A showed ED50 values of 76 and 62 nM for PA and PI labeling, respectively. Peptide corticotropin-releasing factor (CRF) (0.1 microM) did not affect the stimulatory effect of AVP-A on PA and PI labeling. These data suggest that stimulation of PI metabolism in corticotrophs may be one of the early events involved in the stimulation of ACTH release induced by vasopressin.

Animals↗
PubMed1986

Spermine antagonises the effects of dexamethasone, glucagon and cyclic AMP in increasing the activity of phosphatidate phosphohydrolase in isolated rat hepatocytes.

Rat hepatocytes were incubated in monolayer culture, under serum free conditions, for 8 h. Glucagon (10 nM), 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (100 microM) and dexamethasone (100 nM) increased the activity of phosphatidate phosphohydrolase by approx. 2-, 3.6- and 3.3-fold, respectively. Spermine alone had no significant effect. Spermine (2.5 mM) almost completely inhibited the glucagon induced increase in phosphohydrolase activity. It only partially inhibited the dexamethasone and cyclic AMP mediated inductions. Spermidine had no significant effect in this respect. The results are discussed in relation to the known effects of polyamines on glycerolipid synthesis, in particular, and on intermediary metabolism.

Animals↗
PubMed1986

Insulin antagonises the growth hormone-mediated increase in the activity of phosphatidate phosphohydrolase in isolated rat hepatocytes.

Rat hepatocytes were incubated in monolayer culture, under serum-free conditions for 8 h. Rat growth hormone (up to 100 nM) increased the activity of phosphatidate phosphohydrolase by up to 47%. Insulin (500 pM or 35 nM), cycloheximide or actinomycin D reversed this effect. The ability of growth hormone to modify the effects of insulin is discussed in relation to the control of the phosphohydrolase activity and glycerolipid synthesis.

Animals↗