scholarly journals Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

2021 ◽  
Vol 7 ◽  
Author(s):  
Jiayu Wu ◽  
Johan W. M. Heemskerk ◽  
Constance C. F. M. J. Baaten
Keyword(s):  
Platelet Function ◽  
Platelet Membrane ◽  
Comprehensive Overview ◽  
Activated Platelets ◽  
Platelet Membrane Receptor ◽  
Proteolytic Activities ◽  
Signaling Receptors ◽  
Different Origins ◽  
Cytosolic Receptor ◽  
Platelet Functions

The activities of adhesion and signaling receptors in platelets are controlled by several mechanisms. An important way of regulation is provided by proteolytic cleavage of several of these receptors, leading to either a gain or a loss of platelet function. The proteases involved are of different origins and types: (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. We provide a comprehensive overview of the proteases acting on the platelet membrane. We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. The review focuses on coagulation-related proteases, plasmin, matrix metalloproteinases, ADAM(TS) isoforms, cathepsins, caspases, and calpains. We also describe how the proteolytic activities are determined by different platelet populations in a thrombus and conversely how proteolysis contributes to the formation of such populations.

Properties of Fibrinogen Cleaved by Jararhagin, a Metalloproteinase from the Venom of Bothrops jararaca

1994 ◽  
Vol 72 (02) ◽  
pp. 244-249 ◽  
Author(s):  
Aura S Kamiguti ◽  
Joseph R Slupsky ◽  
Mirko Zuzel ◽  
Charles R M Hay
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Human Fibrinogen ◽  
Activated Platelets ◽  
Bothrops Jararaca ◽  
Platelet Binding ◽  
Fibrin Monomers ◽  
Fibrinogen Molecule

SummaryHaemorrhagic metalloproteinases from Bothrops jararaca and other venoms degrade vessel-wall and plasma proteins involved in platelet plug and fibrin clot formation. These enzymes also cause proteolytic digestion of fibrinogen which has been suggested to cause defective platelet function. Fibrinogen degradation by jararhagin, a metalloproteinase from B. jararaca, and the effect of jararhagin fibrinogenolysis on both platelet aggregation and fibrin clot formation were investigated. Jararhagin was found to cleave human fibrinogen in the C-terminal region of the Aα-chain giving rise to a 285-290 kDa fibrinogen molecule lacking the Aα-chain RGD 572-574 platelet-binding site. Platelet binding and aggregation of ADP-activated platelets is unaffected by this modification. This indicates that the lost site is not essential for platelet aggregation, and that the remaining platelet binding sites located in the N-terminal portion of Aα chains (RGD 95-97) and the C-terminal of γ chains (dodecapeptide 400-411) are unaffected by jararhagin-digestion of fibrinogen. Fibrin clot formation with thrombin of this remnant fibrinogen molecule was defective, with poor polymerization of fibrin monomers but normal release of FPA. The abnormal polymerization could be explained by the loss of one of the two complementary polymerization sites required for side-by-side association of fibrin protofibrils. Jararhagin-induced inhibition of platelet function, an important cause of haemorrhage in envenomed patients, is not caused by proteolysis of fibrinogen, as had been thought, and the mechanism remains to be elucidated.

A Comparison of the Effect of Decorsin and Two Disintegrins, Albolabrin and Eristostatin, on Platelet Function

1995 ◽  
Vol 74 (05) ◽  
pp. 1316-1322 ◽  
Author(s):  
Mary Ann McLane ◽  
Jagadeesh Gabbeta ◽  
A Koneti Rao ◽  
Lucia Beviglia ◽  
Robert A Lazarus ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Sequence Similarity ◽  
Platelet Aggregation Inhibitors ◽  
Antiplatelet Drug ◽  
Rgd Sequence ◽  
Fibrinogen Receptor ◽  
Activated Platelets

SummaryNaturally-occurring fibrinogen receptor antagonists and platelet aggregation inhibitors that are found in snake venom (disintegrins) and leeches share many common features, including an RGD sequence, high cysteine content, and low molecular weight. There are, however, significant selectivity and potency differences. We compared the effect of three proteins on platelet function: albolabrin, a 7.5 kDa disintegrin, eristostatin, a 5.4 kDa disintegrin in which part of the disintegrin domain is deleted, and decorsin, a 4.5 kDa non-disintegrin derived from the leech Macrobdella decora, which has very little sequence similarity with either disintegrin. Decorsin was about two times less potent than albolabrin and six times less potent than eristostatin in inhibiting ADP- induced human platelet aggregation. It had a different pattern of interaction with glycoprotein IIb/IIIa as compared to the two disintegrins. Decorsin bound with a low affinity to resting platelets (409 nM) and to ADP-activated platelets (270 nM), and with high affinity to thrombin- activated platelets (74 nM). At concentrations up to 685 nM, it did not cause expression of a ligand-induced binding site epitope on the (β3 subunit of the GPIIb/IIIa complex. It did not significantly inhibit isolated GPIIb/IIIa binding to immobilized von Willebrand Factor. At low doses (1.5-3.0 μg/mouse), decorsin protected mice against death from pulmonary thromboembolism, showing an effect similar to eristostatin. This suggested that decorsin is a much more potent inhibitor of platelet aggregation in vivo than in vitro, and it may have potential as an antiplatelet drug.

Effects of Halothane on Platelet Function

1980 ◽  
Vol 44 (03) ◽  
pp. 143-145 ◽  
Author(s):  
J Dalsgaard-Nielsen ◽  
J Gormsen
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Halothane Anaesthesia ◽  
Inhibition Of Platelet Aggregation ◽  
Transient Impairment ◽  
High Concentrations ◽  
Uptake And Release ◽  
Platelet Functions

SummaryHuman platelets in platelet rich plasma (PRP) incubated at 37° C with 0.3–2% halothane for 5–10 min lost the ability to aggregate with ADP, epinephrine and collagen.At the same time uptake and release of 14C-serotonin was inhibited. When halothane supply was removed, platelet functions rapidly returned to normal. However, after high concentrations of halothane, the inhibition of platelet aggregation was irreversible or only partially reversible.The results suggest that halothane anaesthesia produces a transient impairment of platelet function.

EFFECT OF DDAVP ON PRIMARY HEMOSTASIS WITH CONGENITAL AFIBRINOGENEMIA

1987 ◽  
Author(s):  
M Taki ◽  
M Inagaki ◽  
T Miura ◽  
N Saito ◽  
T Meguro ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Retention Rate ◽  
Platelet Membrane ◽  
Bleeding Tendency ◽  
Primary Hemostasis ◽  
Prolonged Bleeding Time ◽  
Before And After ◽  
Congenital Afibrinogenemia ◽  
Von Willebrand ◽  
Platelet Functions

It has been reported recently that DDAVP might be an useful tool in the therapy and prevention of bleeding in patients with congenital afibrinogenemia (CA).To study the mechanism of its efficacy, changes in the platelet functions of a patient with CA were examined prior to, and one hour after, the infusion of DDAVP (0.4 μg/Kg). A patient with Glanzmann's thrombasthenia (GT) was also examined, to allow a study of the role of platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa), a deficient platelet in GT, in the resulting effects of the drug. When both patients were infused with DDAVP, the level of plasma von Willebrand factor (vWF) increased two- to fourfold, accompanied by an enhancement of ristocetin-induced platelet agglutination. The level of plasma fibrinogen was never changed.The prolonged bleeding time observed was markedly improved only in the CA patient, remaining unchanged in the GT patient, after the infusion of DDAVP. This indicates that DDAVP is effective in diminishing the bleeding tendency in CA, but not in GT. Among the platelet functions tested, only the platelet retention rate on glass beads, ADP-induced platelet aggregation and collagen-induced platelet aggregation improved in CA, each remaining unchanged in GT. In particular, collagen-induced platelet aggregation was markedly improved in the CA patient. However, the platelet adhesion to collagen (50 μg/ml)-Sepharose remained normal, both before and after the infusion of DDAVP in CA.These results suggest that an increase in the plasma vWF level and the existence of platelet membrane GPIIb/IIIa may be necessary for the improvement of primary hemostasis, after the infusion of DDAVP. The vWF-mediated platelet aggregation by collagen or ADP may produce this effect in the CA patient.

scholarly journals Interaction of platelet plasma membranes with thrombin-activated platelets

Blood ◽  
1981 ◽  
Vol 57 (2) ◽  
pp. 305-312 ◽  
Author(s):  
HR Prasanna ◽  
HH Edwards ◽  
DR Phillips
Keyword(s):  
Human Erythrocyte ◽  
Plasma Membranes ◽  
Membrane Binding ◽  
Human Platelets ◽  
Platelet Membrane ◽  
Erythrocyte Membranes ◽  
Functional Sites ◽  
Activated Platelets ◽  
Platelet Membranes ◽  
Human Erythrocyte Membranes

Abstract This study described the binding of platelet plasma membranes to either control or thrombin-activated platelets. Glycoproteins in plasma membranes isolated from human platelets were labeled by oxidation with periodate followed by reduction with [3H]NaBH4. Labeled membranes were incubated with either control or thrombin-activated platelets. The amount of membranes bound was measured by separating platelets with bound membranes from solution by rapid centrifugation through 27% sucrose and determining the amount of radioactivity associated with platelets. Five- to sevenfold more membranes bound to thrombin- activated platelets than to control platelets. This enhanced binding of labeled membranes was completely inhibited by an excess of unlabeled platelet membranes. Human erythrocyte membranes had little affinity for either washed or thrombin-activated platelets and therefore did not compete for platelet-membrane binding. Binding of platelet membranes to thrombin-treated platelets was inhibited by prior incubation of the platelets with PGI2 suggesting that the enhanced binding of membranes was to activated platelets. This study demonstrates that the purified platelet membranes have functional sites that can mediate membrane binding to platelets and that quantitation of membrane binding appears to reflect the increased aggregation capability of activated platelets.

Disturbance Of Platelet Function In The Nephrotic Syndrome

1981 ◽  
Author(s):  
E Walter ◽  
D Deppermann ◽  
K Andrassy ◽  
E Weber
Keyword(s):  
Nephrotic Syndrome ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Kidney Function ◽  
Platelet Function ◽  
Platelet Adhesiveness ◽  
Spontaneous Aggregation ◽  
Spontaneous Platelet Aggregation ◽  
Platelet Functions

Thromboembolic phenomena often (30 %) complicate the nephrotic syndrome. It was therefor investigated, wether disturbed platelet functions play a role in this disease.28 normals, 34 patients with nephrotic syndrome and 18 of them with impaired kidney function were tested. In 20 patients the measurements were repeated after administration of aspirin plus dipyridamo1e.Patients with nephrotic syndrome showed in comparison to normals the following changes: 1. increased platelet count (p < 0.01), 2. enhanced platelet adhesiveness (Wright-test: p < 0.001), 3. increased spontaneous aggregation (PAT I: p < 0.001; PAT III: p < 0.01), 4. enhanced PF 4-activity (heparin neutralisation: p < 0.001), 5. elevated β TG-levels only in impaired kidney function. There was no difference in the reaction of platelets against ADP as well as collagen. The changes in platelet function correlated with the severity of the nephrotic syndrome (proteinurea, hypalbuminaemia, hyperlipo- proteinaemia). After aspirin plus dipyridamole administration spontaneous platelet aggregation and adhesiveness were normalized.There is a disturbance of platelet function in patients with nephrotic syndrome, which can be reversed with antiaggregating agents.

scholarly journals Adequate Platelet Function Inhibition Confirmed by Two Inductive Agents Predicts Lower Recurrence of Ischemic Stroke/Transient Ischemic Attack

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Lulu Zhang ◽  
Xiaowei Hu ◽  
Juehua Zhu ◽  
Xiuying Cai ◽  
Yan Kong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Aggregation Rate ◽  
Function Analyzer ◽  
Ischemic Attack ◽  
Platelet Function Analyzer ◽  
Platelet Functions

Background. The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective. To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method. The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result. Cut-off values of adequate platelet function inhibition were MARADP < 35% and MARAA < 35%. Data showed that antiplatelet therapy could reduce the maximum aggregation rate. More importantly, adequate platelet function inhibition of either MARADP or MARAA was not associated with the recurrence of stroke/TIA, but adequate platelet function inhibition of not only MARADP but also MARAA predicts lower recurrence (0/121 (0.00%) versus 18/459 (3.92%), P = 0.0188). Conclusion. The platelet function tested by PL-11 demonstrated that adequate inhibition of both MARADP and MARAA could predict lower risk of ischemic stroke/TIA recurrence.

scholarly journals Effect of irisin on metabolic and platelet functions in type 2 diabetic rats: role of soluble receptor of advanced glycation end products (sRAGE)

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Sherif W. Mansour ◽  
Mai M. Hasan ◽  
Hossam E. Salah ◽  
Talal El-Deep ◽  
Samia Hussein ◽  
...  
Keyword(s):  
Platelet Function ◽  
Rat Model ◽  
Mean Platelet Volume ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Platelet Volume ◽  
Distribution Width ◽  
Type 2 Diabetic ◽  
Platelet Functions

Abstract Background Irisin is an adipomyokine with a promising potential for the treatment of metabolic disturbances and endothelial dysfunction. This study aimed to explore the effect of irisin on metabolic and platelet functions, and to explore the possible involvement of soluble receptor of advanced glycation end product (sRAGE) in the type 2 diabetes mellitus (T2DM) rat model. Thirty-three adult male albino rats were divided into three groups: normal control, vehicle-treated T2DM group, and irisin-treated T2DM. At the end of the study period, metabolic parameters, platelet count, mean platelet volume, platelet distribution width, plateletcrit, and serum sRAGE were determined. Results Irisin significantly improved platelet function and metabolic derangements induced by T2DM and significantly increased sRAGE. sRAGE was significantly negatively associated with platelet function parameters and some glucometabolic parameters. Additionally, mean platelet volume showed a significant predictive value for the change in serum sRAGE. Conclusions Irisin could have a protective role against diabetes-induced platelet dysfunction by increasing sRAGE levels, indicating the potential beneficial effects of sRAGE in the type 2 diabetic rat model.

scholarly journals Doxorubicin contributes to thrombus formation and vascular injury by interfering with platelet function

2020 ◽  
Vol 319 (1) ◽  
pp. H133-H143 ◽  
Author(s):  
Haichen Lv ◽  
Ruopeng Tan ◽  
Jiawei Liao ◽  
Zhujing Hao ◽  
Xiaolei Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Platelet Aggregation ◽  
Vascular Injury ◽  
Platelet Function ◽  
Thrombus Formation ◽  
Platelet Activity ◽  
Vascular Toxicity ◽  
Platelet Functions

Doxorubicin therapy in mice (antitumor dosage) markedly enhanced platelet functions measured as agonist-induced platelet aggregation, degranulation, and adhesion to endothelial cells, actions leading to thrombus formation and thrombosis-independent vascular injury. Clopidogrel treatment ameliorated thrombus formation and vascular toxicity induced by doxorubicin via inhibiting platelet activity.

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