scholarly journals A trypsin-like platelet protease propagates protease-activated receptor-1 cleavage and platelet activation

1998 ◽  
Vol 336 (2) ◽  
pp. 283-285 ◽  
Author(s):  
Frederick A. OFOSU ◽  
John FREEDMAN ◽  
Lori DEWAR ◽  
Yinqi SONG ◽  
John W. FENTON
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
G Protein ◽  
Platelet Activation ◽  
Trypsin Inhibitor ◽  
Cysteine Proteases ◽  
Serine Protease Inhibitor ◽  
Soybean Trypsin Inhibitor ◽  
Perivascular Cells ◽  
Protease Activated Receptor 1

Protease-activated receptor-1 (PAR-1) is a G-protein-linked receptor on platelets and perivascular cells activated by α-thrombin and the PAR-1-activating peptide, SFLLRN. α-Thrombin activates PAR-1 by cleaving it at R41–S42 to release the 41-residue peptide TR(1–41). Unexpectedly, platelet activation with SFLLRN was also associated with PAR-1 cleavage and the release of TR(1–41). Both PAR-1 cleavage and platelet activation resulting from SFLLRN addition to platelets were markedly inhibited by the serine protease inhibitor 4,2-(aminoethyl)-benzene sulphonylfluoride·HCl (pefabloc SC) and soybean trypsin inhibitor, but not by inhibitors of calpain, cysteine proteases or metalloproteases. Thus, a trypsin-like platelet protease propagates SFLLRN-dependent PAR-1 cleavage and platelet activation.

scholarly journals 3' Noncoding sequences of the CTA 1 gene enhance expression of the recombinant serine protease inhibitor, CPTI II, in Saccharomyces cerevisiae.

1996 ◽  
Vol 43 (3) ◽  
pp. 525-529 ◽  
Author(s):  
M Stankiewicz ◽  
B Rempoła ◽  
M Fikus
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Trypsin Inhibitor ◽  
Yeast Strain ◽  
Serine Protease Inhibitor ◽  
Expression Cassette ◽  
Noncoding Sequences ◽  
Gene Coding

Expression of the gene coding for the recombinant trypsin inhibitor, CPTI II, was enhanced tenfold when yeast transcription terminating sequences were added to the expression cassette of the pJK6 yeast vector. The yield was further increased about 20% in the BJ5464 yeast strain, defective in vacuolar proteases.

Serine Protease Inhibitor Kazal Type 1 (SPINK1): Beyond the Trypsin Inhibitor

2009 ◽  
Vol 5 (2) ◽  
pp. 110-116 ◽  
Author(s):  
Masaki Ohmuraya ◽  
Nobuyuki Ozaki ◽  
Masahiko Hirota ◽  
Hideo Baba ◽  
Ken-ichi Yamamura
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Trypsin Inhibitor ◽  
Serine Protease Inhibitor

The Influence of a Serine Protease Inhibitor, Nafamostat Mesilate, on Plasma Coagulation, and Platelet Activation during Experimental Extracorporeal Life Support (ECLS)

1998 ◽  
Vol 79 (02) ◽  
pp. 342-347 ◽  
Author(s):  
Maria Skogby ◽  
Lars Göran Friberg ◽  
Lilian Tengborn ◽  
Hans Wadenvik ◽  
Karin Mellgren
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Platelet Activation ◽  
Life Support ◽  
Serine Protease Inhibitor ◽  
Platelet Membrane ◽  
Nafamostat Mesilate ◽  
Plasma Coagulation ◽  
Initial Bolus ◽  
Pai 1

SummaryIntroduction: During extracorporeal circulation the contact between blood and the artificial surface of the circuit induces several changes in the hemostatic system. The objective of the present study was to assess the effect of a serine protease inhibitor – Nafamostat mesilate (FUT-175) – on coagulation and on platelets during experimental extracorpo-real circulation. Methods: Two identical Extra Corporeal Life Support (ECLS) circuits were primed with fresh, heparinized human blood and circulated for 24 h. FUT-175 was added to one of the paired circuits and the other was used as a control. The following FUT-175 concentrations were employed: (1) 7.1 mg/l/h, (2) 14.2 mg/l/h, (3) 14.2 mg/l/h + 85.5 mg given as an initial bolus, (4) 28.5 mg/l/h + 171 mg given as an initial bolus. Blood samples were collected from the circuits before the start of the perfusion and at 0.5, 1, 3, 12, and 24 h of perfusion, and analysed for platelet count, plasma betathromboglobulin ( -TG), platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa expression, thrombin/ antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2), fibrinogen, D-dimer, and plasminogen activator inhibitor 1 activity (PAI-1). Results: Significantly higher platelet membrane GPIb expression and lower plasma -thromboglobulin levels were observed in the circuits holding FUT-175, suggesting a lower degree of platelet activation. Also, a reduced activation of the coagulation system was observed in the “FUT-circuits”, as reflected by the levels of F1+2 and TAT, and the PAI-1 activity that was rapidly inactivated. Conclusion: FUT-175 reduces the activation of platelets and plasma coagulation in an in vitro ECLS model.

scholarly journals Aprotinin Inhibits Thrombin Generation by Inhibition of the Intrinsic Pathway, but is not a Direct Thrombin Inhibitor

TH Open ◽  
2021 ◽  
Vol 05 (03) ◽  
pp. e363-e375
Author(s):  
Ton Lisman ◽  
Jelle Adelmeijer ◽  
Dana Huskens ◽  
Joost C. M. Meijers
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Tissue Factor ◽  
Platelet Activation ◽  
Surgical Procedures ◽  
Thrombin Generation ◽  
Serine Protease Inhibitor ◽  
Thrombin Inhibitor ◽  
Clot Lysis ◽  
Intrinsic Pathway

Abstract Background Aprotinin is a broad-acting serine protease inhibitor that has been clinically used to prevent blood loss during major surgical procedures including cardiac surgery and liver transplantation. The prohemostatic properties of aprotinin likely are related to its antifibrinolytic effects, but other mechanisms including preservation of platelet function have been proposed. Aim Here we assessed effects of aprotinin on various hemostatic pathways in vitro, and compared effects to tranexamic acid(TXA), which is an antifibrinolytic but not a serine protease inhibitor. Methods We used plasma-based clot lysis assays, clotting assays in whole blood, plasma, and using purified proteins, and platelet activation assays to which aprotinin or TXA were added in pharmacological concentrations. Results Aprotinin and TXA dose-dependently inhibited fibrinolysis in plasma. Aprotinin inhibited clot formation and thrombin generation initiated via the intrinsic pathway, but had no effect on reactions initiated by tissue factor. However, in the presence of thrombomodulin, aprotinin enhanced thrombin generation in reactions started by tissue factor. TXA had no effect on coagulation. Aprotinin did not inhibit thrombin, only weakly inhibited the TF-VIIa complex and had no effect on platelet activation and aggregation by various agonists including thrombin. Aprotinin and TXA inhibited plasmin-induced platelet activation. Conclusion Pharmacologically relevant concentrations of aprotinin inhibit coagulation initiated via the intrinsic pathway. The antifibrinolytic activity of aprotinin likely explains the prohemostatic effects of aprotinin during surgical procedures. The anticoagulant properties may be beneficial during surgical procedures in which pathological activation of the intrinsic pathway, for example by extracorporeal circuits, occurs.

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