Lysophosphatidic Acid Activates Phosphoinositide 3-Kinase and Phospholipase C in Human Platelets: Inhibitory Effects of Wortmannin on Phosphoinositide 3-Kinase and Aggregation

1995 ◽  
Vol 211 (2) ◽  
pp. 484-490 ◽  
Author(s):  
J. Zhang ◽  
S.E. Rittenhouse
Keyword(s):  
Phospholipase C ◽  
Lysophosphatidic Acid ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Phosphoinositide 3 Kinase

Lysophosphatidic acid induces protein tyrosine phosphorylation in the absence of phospholipase C activation in human platelets

Platelets ◽  
1997 ◽  
Vol 8 (2) ◽  
pp. 181-188
Author(s):  
M. Torti ◽  
E. Tolnai Festetics ◽  
A. Bertoni ◽  
R. Moratti ◽  
C. Balduini ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Lysophosphatidic Acid ◽  
Human Platelets ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

Lysophosphatidic acid induces protein tyrosine phosphorylation in the absence of phospholipase C activation in human platelets

Platelets ◽  
1997 ◽  
Vol 8 (2) ◽  
pp. 181-187
Author(s):  
M. Torti ◽  
E. Tolnai Festetics ◽  
A. Bertoni ◽  
R. Moratti ◽  
C. Balduini ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Lysophosphatidic Acid ◽  
Human Platelets ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

Regulation of platelet phospholipase C

1988 ◽  
Vol 320 (1199) ◽  
pp. 299-311 ◽  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Phospholipase C ◽  
Phorbol Esters ◽  
Human Platelets ◽  
Direct Effects ◽  
Inhibitory Effects ◽  
Factors Affecting ◽  
Kinase C

We have investigated factors affecting the activation of phospholipase C in human platelets. Prior exposure of platelets to phorbol esters that stimulate protein kinase C inhibits the activation of phospholipase C in response to a variety of receptor-directed agonists, including x- and y-thrombin and thromboxane A 2 analogues. Such activation has been assayed by measurements of accumulated InsP 3 (including Ins(l,4,5)P 3 and Ins(l,3,4)P 3 ) and PtdOH. Inhibition is not overcome by Ca 2+ ionophores, and substances that block or mimic Na+-H + exchange neither block nor mimic these inhibitory effects. Cyclic AMP and cyclic GMP, other agents known to inhibit phospholipase C activation, do not accumulate in platelets exposed to phorbol esters. Although a portion of the effects of phorbol ester on InsP 3 accumulation may be explained by 5-phosphomonoesterase activity, it is likely that more direct effects on phospholipase C are being exerted as well, and contribute the major inhibitory route. We have examined the susceptibility of adenylyl cyclase-associated G 1 and ‘G p ’- activated phospholipase C to inhibitory ADP-ribosylation by pertussis toxin-derived enzyme (S 1 protomer) administered to saponin-permeabilized platelets. The effects of a-thrombin on adenylyl cyclase can be inhibited by up to 50% by S 1 at which point inhibition of phospholipase C is barely detectable. Thromboxane A 2 analogues, which do not affect adenylyl cyclase (G 1 ), stimulate phospholipase C; this effect is not impaired by Sr We therefore propose that the inhibitory effects of phorbol esters on the activation of phospholipase C are not mediated primarily by effects on G 1 .

Lysophosphatidic acid induces protein tyrosine phosphorylation in the absence of phospholipase C activation in human platelets

Platelets ◽  
1997 ◽  
Vol 8 (2-3) ◽  
pp. 181-187 ◽  
Author(s):  
M. Torti ◽  
E. Tolnai Festetics ◽  
A. Bertoni ◽  
R. Moratti ◽  
C. Balduini ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Lysophosphatidic Acid ◽  
Human Platelets ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

The Effects of Brinolase (Fibrinolytic Enzyme from Aspergillus Oryzae) on Platelet Aggregation of Dog and Man

1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage
Keyword(s):  
Platelet Aggregation ◽  
Aspergillus Oryzae ◽  
Degradation Products ◽  
Blood Platelet ◽  
Human Platelets ◽  
Fibrinolytic Enzyme ◽  
Inhibitory Effects ◽  
Blood Platelet Aggregation

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.

Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change

1984 ◽  
Vol 52 (03) ◽  
pp. 333-335 ◽  
Author(s):  
Vider M Steen ◽  
Holm Holmsen
Keyword(s):  
Inhibitory Action ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Early Step ◽  
Stimulus Response ◽  
Sequential Relationship

SummaryThe inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E1 or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE1 and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.

Protocatechuic Acid Protects Platelets from Apoptosis via Inhibiting Oxidative Stress-Mediated PI3K/Akt/GSK3β Signaling

2021 ◽  
Author(s):  
Fuli Ya ◽  
Kongyao Li ◽  
Hong Chen ◽  
Zezhong Tian ◽  
Die Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Protocatechuic Acid ◽  
Human Platelets ◽  
Ros Generation ◽  
Inhibitory Effects ◽  
Platelet Apoptosis ◽  
Phosphatidylserine Exposure ◽  
Underlying Mechanisms

AbstractOxidative stress plays crucial roles in initiating platelet apoptosis that facilitates the progression of cardiovascular diseases (CVDs). Protocatechuic acid (PCA), a major metabolite of anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g), exerts cardioprotective effects. However, underlying mechanisms responsible for such effects remain unclear. Here, we investigate the effect of PCA on platelet apoptosis and the underlying mechanisms in vitro. Isolated human platelets were treated with hydrogen peroxide (H2O2) to induce apoptosis with or without pretreatment with PCA. We found that PCA dose-dependently inhibited H2O2-induced platelet apoptosis by decreasing the dissipation of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and decreasing phosphatidylserine exposure. Additionally, the distributions of Bax, Bcl-xL, and cytochrome c mediated by H2O2 in the mitochondria and the cytosol were also modulated by PCA treatment. Moreover, the inhibitory effects of PCA on platelet caspase-3 cleavage and phosphatidylserine exposure were mainly mediated by downregulating PI3K/Akt/GSK3β signaling. Furthermore, PCA dose-dependently decreased reactive oxygen species (ROS) generation and the intracellular Ca2+ concentration in platelets in response to H2O2. N-Acetyl cysteine (NAC), a ROS scavenger, markedly abolished H2O2-stimulated PI3K/Akt/GSK3β signaling, caspase-3 activation, and phosphatidylserine exposure. The combination of NAC and PCA did not show significant additive inhibitory effects on PI3K/Akt/GSK3β signaling and platelet apoptosis. Thus, our results suggest that PCA protects platelets from oxidative stress-induced apoptosis through downregulating ROS-mediated PI3K/Akt/GSK3β signaling, which may be responsible for cardioprotective roles of PCA in CVDs.

Possible regulation of phospholipase C activity in human platelets by phosphatidylinositol 4′,5′-bisphosphate

1984 ◽  
Vol 228 (1) ◽  
pp. 299-308 ◽  
Author(s):  
Gustav Graff ◽  
Nabeel Nahas ◽  
Maria Nikolopoulou ◽  
Viswanathan Natarajan ◽  
Harald H.O. Schmid
Keyword(s):  
Phospholipase C ◽  
Human Platelets ◽  
Phosphatidylinositol 4

FOXD3 inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma through regulation of the PI3K–Akt pathway

2020 ◽  
Vol 98 (6) ◽  
pp. 653-660 ◽  
Author(s):  
Xiaoxing Xie ◽  
Gaoyun Xiong ◽  
Wenjun Chen ◽  
Hongdan Fu ◽  
Mingqian Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Apoptosis ◽  
Inhibitory Effect ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Protein Levels ◽  
Flow Cytometric ◽  
Phosphoinositide 3 Kinase

FOXD3 has been found previously to positively regulate miR-26b, a tumor inhibitor of nasopharyngeal carcinoma (NPC). However, FOXD3’s precise function and associated mechanism of action in NPC have not yet been investigated. In this study, the expression of FOXD3 mRNA and protein was evaluated using RT-qPCR, western blotting, and immunohistochemistry. Protein levels involved in the phosphoinositide 3-kinase – protein kinase B (PI3K–Akt) pathway were assessed by western blot, and cell proliferation was determined by MTT and colony forming assays. Additionally, cell apoptosis was assessed by flow cytometric assay. Finally, the migration and invasion capabilities of the NPC cells were determined using wound healing and Transwell assays. We found that FOXD3 levels were relatively low in NPC tissue and cells, while an increase caused the inhibition of the PI3K–Akt pathway. Functional experiments found that overexpression of FOXD3 suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis in NPC C6661 cells. IGF-1, an activator of the PI3K–Akt pathway, reversed the inhibitory effect of FOXD3. Furthermore, we found upregulation of the PI3K–Akt pathway and upregulation of the inhibitory effects of FOXD3 on C6661 cellular activities. In conclusion, FOXD3 negatively affected the PI3K–Akt pathway to restrain the processes involved in C6661 cell pathology. These findings further exposed the function and downstream axis of FOXD3 in NPC and displayed a promising new target for NPC therapy.

scholarly journals Progesterone-Dependent Induction of Phospholipase C-Related Catalytically Inactive Protein 1 (PRIP-1) in Decidualizing Human Endometrial Stromal Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2883-2893 ◽  
Author(s):  
Joanne Muter ◽  
Paul J. Brighton ◽  
Emma S. Lucas ◽  
Lauren Lacey ◽  
Anatoly Shmygol ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Stromal Cells ◽  
Nuclear Translocation ◽  
Scaffold Protein ◽  
Trophoblast Invasion ◽  
Differentiation Markers ◽  
Endometrial Stromal Cells ◽  
Decidual Cells ◽  
Phosphoinositide 3 Kinase ◽  
Inactive Protein

Decidualization denotes the transformation of endometrial stromal cells into specialized decidual cells. In pregnancy, decidual cells form a protective matrix around the implanting embryo, enabling coordinated trophoblast invasion and formation of a functional placenta. Continuous progesterone (P4) signaling renders decidual cells resistant to various environmental stressors, whereas withdrawal inevitably triggers tissue breakdown and menstruation or miscarriage. Here, we show that PLCL1, coding phospholipase C (PLC)-related catalytically inactive protein 1 (PRIP-1), is highly induced in response to P4 signaling in decidualizing human endometrial stromal cells (HESCs). Knockdown experiments in undifferentiated HESCs revealed that PRIP-1 maintains basal phosphoinositide 3-kinase/Protein kinase B activity, which in turn prevents illicit nuclear translocation of the transcription factor forkhead box protein O1 and induction of the apoptotic activator BIM. By contrast, loss of this scaffold protein did not compromise survival of decidual cells. PRIP-1 knockdown did also not interfere with the responsiveness of HESCs to deciduogenic cues, although the overall expression of differentiation markers, such as PRL, IGFBP1, and WNT4, was blunted. Finally, we show that PRIP-1 in decidual cells uncouples PLC activation from intracellular Ca2+ release by attenuating inositol 1,4,5-trisphosphate signaling. In summary, PRIP-1 is a multifaceted P4-inducible scaffold protein that gates the activity of major signal transduction pathways in the endometrium. It prevents apoptosis of proliferating stromal cells and contributes to the relative autonomy of decidual cells by silencing PLC signaling downstream of Gq protein-coupled receptors.

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