Verapamil inhibits phosphatidic acid formation and modifies phosphoinositide metabolism in stimulated platelets

1990 ◽  
Vol 182 (3) ◽  
pp. 457-464 ◽  
Author(s):  
Sheryl T. Homa ◽  
Shah Nawaz Khan ◽  
Dolores M. Conroy ◽  
Andrew E. Speak ◽  
Anthony D. Smith
Keyword(s):  
Phosphatidic Acid ◽  
Acid Formation ◽  
Phosphoinositide Metabolism

Evidence for two mechanisms of thrombin-induced platelet activation: one proteolytic, one receptor mediated

1989 ◽  
Vol 67 (7) ◽  
pp. 332-336 ◽  
Author(s):  
Archibald McNicol ◽  
Jon M. Gerrard ◽  
D. Euan MacIntyre
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase C ◽  
Platelet Reactivity ◽  
Platelet Activating Factor ◽  
Receptor Activation ◽  
Acid Formation ◽  
Phosphoinositide Metabolism ◽  
Co Addition ◽  
The Individual ◽  
Dual Mechanism

The possibility that thrombin-induced platelet reactivity could occur via both a receptor-related and a proteolytic process was examined. Thrombin elicited the formation of considerably more [32P)phosphatidic acid (an index of phospholipase C catalysed phosphoinositide metabolism) than did platelet activating factor, 5-hydroxytryptamine, ADP, and the thromboxane A2 analogue EP171, when these agents were added either alone or in combination. Co-addition of thrombin and EP171 did not evoke significantly more [32P]phosphatidic acid than did thrombin alone. The protease inhibitor leupeptin, decreased but did not abolish [32P]phosphatidic acid formation elicited by either thrombin alone or thrombin in combination with EP171. The serine protease, trypsin, stimulated an increase in [32P]phosphatidic acid and this effect was additive with that of EP171. This augmentation by trypsin of EP171-induced [32P]phosphatidic acid formation was inhibited by leupeptin. These results are consistent with the concept that thrombin-induced activation of phospholipase C occurs by two distinct mechanisms: one via proteolysis, which is sensitive to leupeptin, and the other via receptor activation, a process shared by EP171. The individual components of this dual mechanism can be mimicked by the co-addition of a receptor-directed agonist (EP171) and a proteolytic agent (trypsin).Key words: platelet, thrombin, proteolysis, phosphoinositide.

Study of the Involvement of Phosphatidic Acid Formation in the Expression of Wound-Responsive Genes in Cotton

Lipids ◽  
2018 ◽  
Vol 53 (6) ◽  
pp. 589-599
Author(s):  
Angeliki Bourtsala ◽  
Ioannis Dafnis ◽  
Angeliki Chroni ◽  
Theodora Farmaki ◽  
Dia Galanopoulou
Keyword(s):  
Phosphatidic Acid ◽  
Acid Formation

The acylation of 1-acyl-sn-glycero-3-phosphate by neuronal nuclei and microsomal fractions of immature rabbit cerebral cortex

1990 ◽  
Vol 68 (3) ◽  
pp. 641-647 ◽  
Author(s):  
R. Roy Baker ◽  
H.-Y. Chang
Keyword(s):  
Cerebral Cortex ◽  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Monounsaturated Fatty Acids ◽  
Acid Formation ◽  
Nuclear Fraction ◽  
Neuronal Nucleus ◽  
Neuronal Nuclei ◽  
Low Concentrations ◽  
Rabbit Cerebral Cortex

The acylation of 1-acyl-sn-glycero-3-phosphate to form phosphatidic acid was studied using a neuronal nuclear fraction N1 and microsomal fractions P3, R (rough), S (smooth), and P (neuronal microsomes from nerve cell bodies) isolated from cerebral cortices of 15-day-old rabbits. The assays contained this lysophospholipid, ATP, CoA, MgCl2, NaF, dithiothreitol, and radioactive palmitate, oleate, or arachidonate. Of the subfractions, N1 and R had the highest specific activities (expressed per micromole phospholipid in the fraction). The rates with oleate were two to four times the values seen for phosphatidic acid formation from sn-[3H]glycero-3-phosphate and oleoyl-CoA. Using oleate or palmitate, fraction R had superior specific rates to N1 at low lysophosphatidic acid concentrations. With increasing lysophospholipid concentrations the specific rates of N1 and R came closer together and maintained at least a twofold superiority over fraction P. Fraction S had the lowest specific rates of phosphatidic acid formation. Fractions N1, R, and P showed a preference for palmitate and oleate over arachidonate, particularly at low concentrations of lysophosphatidic acid. For N1 and R, the preference was also more marked at higher concentrations of fatty acid. Thus a selectivity for saturated and monounsaturated fatty acids was shown in the formation of phosphatidic acid, as was a concentration of acylating activity in the neuronal nucleus and the rough endoplasmic reticulum.Key words: 1-acyl-sn-glycero-3-phosphate, acylation, neuronal nuclei, microsomes, cerebral cortex.

scholarly journals Phosphoinositide metabolism and the morphology of human erythrocytes.

1984 ◽  
Vol 98 (6) ◽  
pp. 1992-1998 ◽  
Author(s):  
J E Ferrell ◽  
W H Huestis
Keyword(s):  
Phosphatidic Acid ◽  
Shape Change ◽  
Human Erythrocytes ◽  
Phosphoinositide Metabolism ◽  
Nutrient Supplementation ◽  
Related Process

ATP-depleted human erythrocytes lose their smooth discoid shape and adopt a spiny, crenated form. This shape change coincides with the conversion of phosphatidylinositol-4,5-bisphosphate to phosphatidylinositol and phosphatidic acid to diacylglycerol. Both crenation and lipid dephosphorylation are accelerated by iodoacetamide, and both are reversed by nutrient supplementation. The observed changes in lipid populations should shrink the membrane inner monolayer by 0.6%, consistent with estimates of bilayer imbalance in crenated cells. These observations suggest that metabolic crenation arises from a loss of inner monolayer area secondary to the degradation of phosphatidylinositol-4,5-bisphosphate and phosphatidic acid. A related process, crenation after Ca2+ loading, appears to arise from a loss inositides by a different pathway.

Fatty Acid Binding Protein: Stimulation of Microsomal Phosphatidic Acid Formation

1997 ◽  
Vol 341 (1) ◽  
pp. 112-121 ◽  
Author(s):  
Christopher A. Jolly ◽  
Timothy Hubbell ◽  
William D. Behnke ◽  
Friedhelm Schroeder
Keyword(s):  
Fatty Acid ◽  
Phosphatidic Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Acid Formation ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Stimulation Of

Shape control in the human red cell

1986 ◽  
Vol 80 (1) ◽  
pp. 281-298
Author(s):  
L. Backman
Keyword(s):  
Phosphatidic Acid ◽  
Shape Control ◽  
Control Mechanism ◽  
Cytoskeletal Proteins ◽  
Phosphoinositide Metabolism ◽  
Red Cell ◽  
Spherical Form ◽  
Protein Dephosphorylation ◽  
Shape Changes ◽  
Bilayer Couple

When the human red cell consumes its ATP, the cell loses its discoid character in favour of a spiculated and eventually a spherical form. This discocyte-echinocyte transformation parallels both degradation of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid but not dephosphorylation of cytoskeletal proteins. Dephosphorylation of both spectrin and band 3 lags behind metabolic crenation. Exogenous vanadate accelerates both shape changes and lipid dephosphorylation in a parallel manner during metabolic depletion. In contrast to its effect on lipids, vanadate reduces the rate of protein dephosphorylation. These observations strongly support a shape control mechanism in the red cell, based on phosphoinositide metabolism and compatible with a bilayer-couple model.

scholarly journals The action of the protein kinase C inhibitor, staurosporine, on human platelets. Evidence against a regulatory role for protein kinase C in the formation of inositol trisphosphate by thrombin

1988 ◽  
Vol 249 (2) ◽  
pp. 345-350 ◽  
Author(s):  
S P Watson ◽  
J McNally ◽  
L J Shipman ◽  
P P Godfrey
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidic Acid ◽  
Phorbol Esters ◽  
Inositol Phosphates ◽  
Protein A ◽  
Polymyxin B ◽  
Human Platelets ◽  
Phosphoinositide Metabolism ◽  
Kinase C

The ability of several putative inhibitors of protein kinase C (PKC) to block dioctanoylglycerol (DC8)-induced phosphorylation of a 47 kDa protein (a recognized substrate for PKC) in human platelets was investigated. Staurosporine (1 microM) caused complete inhibition of phosphorylation, whereas the other reagents were either inactive (polymyxin B) or gave only partial inhibition (C-1, H-7, tamoxifen). Staurosporine (1 microM) fully inhibited the phosphorylation of the 47 kDa protein in platelets challenged with thrombin, but also inhibited the phosphorylation of a 20 kDa protein which is a substrate for myosin light-chain kinase. The inhibition of both kinases by staurosporine was associated with the inhibition of thrombin-induced secretion of ATP and 5-hydroxytryptamine and a slowing of the aggregation response; staurosporine, however, had no effect on the formation of phosphatidic acid and inositol phosphates induced by thrombin. Staurosporine also reversed the inhibitory action of phorbol esters on thrombin-induced formation of phosphatidic acid. These data are consistent with a role for these two kinases in secretion and aggregation (although there must be additional control signals, since aggregation was only slowed, not inhibited), but suggest that neither kinase is involved in the regulation of phosphoinositide metabolism. This latter conclusion contradicts previous observations that the activation of PKC by phorbol esters or membrane-permeable diacylglycerols alters the apparent activity of both phospholipase C and inositol trisphosphatase. Possible explanations for this discrepancy are discussed.

Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4122-4128 ◽  
Author(s):  
Tomohiro Hitomi ◽  
Juan Zhang ◽  
Liliana M. Nicoletti ◽  
Ana Cristina G. Grodzki ◽  
Maria C. Jamur ◽  
...  
Keyword(s):  
Mast Cell ◽  
Phosphatidic Acid ◽  
Mast Cell Degranulation ◽  
Dominant Negative ◽  
Acid Formation ◽  
Wild Type ◽  
High Affinity ◽  
Phospholipase D1 ◽  
High Affinity Ige Receptor

Abstract To investigate the role of phospholipase D (PLD) in FcϵRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcϵRI stimulation resulted in the activation of both PLD1 and PLD2. However, PLD1 was the source of most of the receptor-induced PLD activity. There was enhanced FcϵRI-induced degranulation only in cells that overexpressed the catalytically inactive PLD1. This dominant-negative PLD1 enhanced FcϵRI-induced tyrosine phosphorylations of early signaling molecules such as the receptor subunits, Syk and phospholipase C-γ which resulted in faster release of Ca2+ from intracellular sources. Therefore, PLD1 negatively regulates signals upstream of the Ca2+ response. However, FcϵRI-induced PLD activation required Syk and was downstream of the Ca2+response, suggesting that basal PLD1 activity rather than that activated by cell stimulation controlled these early signaling events. Dominant-negative PLD1 reduced the basal phosphatidic acid formation in unstimulated cells, which was accompanied by an increase in FcϵRI within the lipid rafts. These results indicate that constitutive basal PLD1 activity by regulating phosphatidic acid formation controls the early signals initiated by FcϵRI aggregation that lead to mast cell degranulation. (Blood. 2004;104:4122-4128)

THE INCORPORATION OF α-GLYCEROPHOSPHATE-32P INTO THE LIPIDS OF RAT BRAIN PREPARATIONS: II. ON THE BIOSYNTHESIS OF MONOPHOSPHOINOSITIDE

1967 ◽  
Vol 45 (1) ◽  
pp. 63-70 ◽  
Author(s):  
F. Possmayer ◽  
K. P. Strickland
Keyword(s):  
Phosphatidic Acid ◽  
Rat Brain ◽  
Isotope Dilution ◽  
Time Course ◽  
Acid Formation ◽  
Dilution Experiments ◽  
Phosphatide Acid

Previous investigations conducted in this laboratory showed a number of differences in the cytosine nucleotide requirement for the incorporation of α-glycerophosphate (α-G32P) into the monophosphoinositide of rat brain preparations compared to the pathway described by Paulus and Kennedy, where α-glycerophosphate → phosphatide acid → CDP-diglyceride → monophosphoinositide, and CTP is specifically required. Experiments were carried out with rat brain preparations to determine the nature of the mechanism whereby CDP-choline is as effective as or more effective than CTP in stimulating the incorporation of α-G32P into monophosphoinositide. Isotope dilution experiments in which unlabeled phosphatidic acid and CDP-diglyceride were used, yielded results consistent with the view that both of these compounds are intermediates in the incorporation of a-G32P into monophosphoinositide stimulated by either CTP or CDP-choline. Time-course experiments where cytosine nucleotides were added either at the beginning or after 20 minutes produced a pattern of labeling which could be fitted into the above interpretation, provided that newly formed radioactive molecules of phosphatide acid could be used selectively and CTP in some way inhibits phosphatide acid formation or accumulation. The latter could account for the observation that monophosphoinositide becomes far more actively labeled than phosphatidic acid in the presence of added CTP.

Sign in / Sign up

Export Citation Format

Share Document