Rates of production and consumption of phosphatidic acid upon thrombin stimulation of human platelets

Tysnes, Ole‐Bjørn; Verhoeven, Adrie J.M.; Holmsen, Holm

doi:10.1111/j.1432-1033.1988.tb14064.x

Cited by 27 publications

(10 citation statements)

References 28 publications

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“…However, this argument is contradicted by the finding of similar levels of 32Pactivities in the PI fractions from both microbubble-stimulated platelets and from unstimulated platelets. Furthermore, the conversion steps in the PPI cycle from PA to PI have been suggested to occur at a slower rate than the steps from PIP2 to PA (13). The unchanged levels of 32P-PIPz, observed in unstimulated platelets are in agreement with this conclusion.…”

Section: Discussionsupporting

confidence: 62%

Microbubble-Induced Phospholipase C Activation Does not Correlate with Platelet Aggregation

et al. 1993

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SummaryThe effect of nitrogen-(N2-)microbubbles on platelets resembles that of common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This paper reports the effect of microbubbles on platelet phospholipase C activity in gelfiltered human platelets prelabelled with [32P]Pi ([32P]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADP. Stimulation of [32P]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p <0.0004) and a significant increase in 32P-activity in the phosphatidic acid (PA) fraction (p <0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p <0.05), but did not enhance the amount of 32P in the platelet [32P]PA fraction. The 32P-radioactivity in the PI-fraction increased with time to a similar extent when [32P]-GFP was stirred for 30 min in absence of microbubbles as it did after 30 min of agonist exposure. There were no significant changes in the [32P]PIP and [32P]PIP2 fractions. Aspirin abolished the microbubble-induced increase in 32P-activity in the PA fraction, but had no significant effect on the reduction in single platelets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles (p <0.05). With epinephrine, however, aspirin did not completely abolish the increase in [32P]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates independent of cyclooxygenase-dependent arachidonic acid metabolites and phospholipase C activation.

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Section: Discussionsupporting

confidence: 62%

Microbubble-Induced Phospholipase C Activation Does not Correlate with Platelet Aggregation

et al. 1993

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“…Freshly drawn venous blood was provided by the Blood Bank (Haukeland University Hospital, Bergen, Norway), and isolated as previously described [50,51]. In brief, blood was collected into a final 0.15 volume of acid citrated dextrose (ACD; 71 mM citric acid, 85 mM Na3-citrate, 100 mM glucose).…”

Section: Methodsmentioning

confidence: 99%

Iodinin (1,6-Dihydroxyphenazine 5,10-Dioxide) from Streptosporangium sp. Induces Apoptosis Selectively in Myeloid Leukemia Cell Lines and Patient Cells

et al. 2013

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Despite recent improvement in therapy, acute myeloid leukemia (AML) is still associated with high lethality. In the presented study, we analyzed the bioactive compound iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from a marine actinomycetes bacterium for the ability to induce cell death in a range of cell types. Iodinin showed selective toxicity to AML and acute promyelocytic (APL) leukemia cells, with EC50 values for cell death up to 40 times lower for leukemia cells when compared with normal cells. Iodinin also successfully induced cell death in patient-derived leukemia cells or cell lines with features associated with poor prognostic such as FLT3 internal tandem duplications or mutated/deficient p53. The cell death had typical apoptotic morphology, and activation of apoptotic signaling proteins like caspase-3. Molecular modeling suggested that iodinin could intercalate between bases in the DNA in a way similar to the anti-cancer drug daunorubicin (DNR), causing DNA-strand breaks. Iodinin induced apoptosis in several therapy-resistant AML-patient blasts, but to a low degree in peripheral blood leukocytes, and in contrast to DNR, not in rat cardiomyoblasts. The low activity towards normal cell types that are usually affected by anti-leukemia therapy suggests that iodinin and related compounds represent promising structures in the development of anti-cancer therapy.

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“…[3H]Inositol was time-dependently incorporated into phosphoinositides up to 300 min. After 150 min incubation, the distribution of 3H radioactivity in Ptdlns (86 %), PtdlnsP (7 %) and PtdInsP2 (6%) became similar to the mass ratio of phosphoinositides [33,35]. To prevent the decrease in platelet responsiveness after long incubation, platelets were labelled for 150 min.…”

Section: Inositol Phospmte Formationmentioning

confidence: 99%

Thrombin induces a biphasic 1,2-diacylglycerol production in human platelets

Suganuma

Matsui

Nozawa

1991

Biochemical Journal

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The 1,2-diacylglycerol (DAG) mass content was measured in thrombin-stimulated human platelets. Thrombin stimulates a biphasic accumulation of DAG, with an early phase reaching a peak at 10 s and a later phase reaching a peak at 2-3 min. The time course of first-phase DAG production corresponded well to that of Ins(1,4,5)P3 formation, which was rapid and transient. The second phase of DAG accumulation occurred after the level of Ins(1,4,5)P3 returned to nearly basal. Thrombin stimulated the decrease in PtdIns and phosphatidylcholine contents. The source of second-phase DAG was examined in platelets prelabelled with three radioactive fatty acids, i.e. arachidonic, palmitic and myristic. Thrombin stimulated the increase in radioactivity of DAG with decline of PtdIns in platelets labelled with [3H]arachidonic acid or [3H]palmitic acid, in which PtdIns was considerably labelled. In contrast, significant accumulation of [3H]DAG was not observed in [3H]myristic acid-labelled platelets, in which PtdIns was poorly labelled. In platelets prelabelled with [3H]inositol, an increase in InsP in response to thrombin was seen for more than 5 min. In contrast, upon stimulation, significant increases in [3H]phosphocholine and [3H]choline were not observed in [methyl-3H]choline-labelled platelets. Thrombin induced a small production of phosphatidylethanol, when ethanol was present during stimulation. However, the formation of DAG and phosphatidic acid was not significantly affected by ethanol. These results suggest that thrombin stimulates a biphasic accumulation of DAG, initially from PtdInsP2 and later from PtdIns in human platelets.

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Rates of production and consumption of phosphatidic acid upon thrombin stimulation of human platelets

Cited by 27 publications

References 28 publications

Microbubble-Induced Phospholipase C Activation Does not Correlate with Platelet Aggregation

Microbubble-Induced Phospholipase C Activation Does not Correlate with Platelet Aggregation

Iodinin (1,6-Dihydroxyphenazine 5,10-Dioxide) from Streptosporangium sp. Induces Apoptosis Selectively in Myeloid Leukemia Cell Lines and Patient Cells

Thrombin induces a biphasic 1,2-diacylglycerol production in human platelets

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