scholarly journals Functional role of the polysaccharide component of rabbit thrombomodulin proteoglycan. Effects on inactivation of thrombin by antithrombin, cleavage of fibrinogen by thrombin and thrombin-catalysed activation of factor V

1990 ◽  
Vol 270 (2) ◽  
pp. 419-425 ◽  
Author(s):  
M C Bourin ◽  
U Lindahl
Keyword(s):  
Protein C ◽  
Inhibitory Effect ◽  
Factor V ◽  
Promoting Effect ◽  
Activation Kinetics ◽  
Polysaccharide Chain ◽  
Factor Va ◽  
Kinetics Of ◽  
Similar Sample

Thrombomodulin (TM), a major anticoagulant protein at the vessel wall, serves as a potent cofactor for the activation of Protein C by thrombin. Previous work has indicated that (rabbit) TM is a proteoglycan that contains a single polysaccharide chain, tentatively identified as a sulphated galactosaminoglycan, and furthermore suggested that this component may be functionally related to additional anticoagulant activities expressed by the TM molecule [Bourin, Ohlin, Lane, Stenflo & Lindahl (1988) J. Biol. Chem. 263, 8044-8052]. Results of the present study establish that (enzymic) removal of the polysaccharide chain abolishes the inhibitory effect of TM on thrombin-induced fibrinogen clotting as well as the promoting effect of TM on the inactivation of thrombin by antithrombin, but does not affect the ability of TM to serve as a cofactor in the activation of Protein C. Studies of yet another biological activity of rabbit TM, namely the ability to prevent the activation of Factor V by thrombin [Esmon, Esmon & Harris (1982) J. Biol. Chem. 257, 7944-7947], confirmed that TM markedly delays the conversion of the native 330 kDa Factor V precursor into polypeptide intermediates, and further into the 96 kDa heavy chain and 71-74 kDa light-chain components of activated Factor Va. In contrast, the activation kinetics of a similar sample of Factor V incubated with thrombin in the presence of chondroitinase ABC-digested TM did not differ from that observed in the absence of TM. It is concluded that the inhibitory effect of TM on Factor V activation also depends on the presence of the polysaccharide component on the TM molecule.

β2-Glycoprotein I Modulates the Anticoagulant Activity of Activated Protein C on the Phospholipid Surface

1996 ◽  
Vol 75 (01) ◽  
pp. 049-055 ◽  
Author(s):  
Tatsuyuki Mori ◽  
Hiroyuki Takeya ◽  
Junji Nishioka ◽  
Esteban C Gabazza ◽  
Koji Suzuki
Keyword(s):  
Protein C ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Protein S ◽  
Inhibitory Effect ◽  
Factor V ◽  
Clotting Time ◽  
Factor Va ◽  
Glycoprotein I ◽  
Prothrombinase Activity

SummaryThe objective of this study was to determine whether (β2-glycoprotein I (β2GPI) has procoagulant activity by inhibiting the anticoagulant activity of activated protein C (APC). β2GPI inhibited significantly the APC-catalyzed inactivation of factor Va in an assay using factor V-deficient plasma and physiological levels of protein S and factor Va. This inhibitory effect was diminished by the addition of increasing concentrations of phospholipids, suggesting that β2GPI competitively inhibits the binding of APC to the phospholipid surface. β2GPI inhibited weakly factor Va- and phospholipid-dependent prothrombinase activity at concentrations similar to those to inhibit APC activity. The depletion of β2GPI from plasma led to only a slight shortening of the diluted Russell’s viper venom-dependent clotting time, but to a strong and significant potentiation of the anticoagulant activity of APC. These results suggest that under certain physiological conditions β2GPI has procoagulant property by inhibiting the phospholipid-dependent APC anticoagulant activity.

scholarly journals ptFVa ( Pseudonaja Textilis Venom-Derived Factor Va) Retains Structural Integrity Following Proteolysis by Activated Protein C

2021 ◽  
Author(s):  
Mark Schreuder ◽  
Xiaosong Liu ◽  
Ka Lei Cheung ◽  
Pieter H. Reitsma ◽  
Gerry A.F. Nicolaes ◽  
...  
Keyword(s):  
Protein C ◽  
Structural Integrity ◽  
Noncovalent Interactions ◽  
Activated Protein C ◽  
Regulatory Mechanisms ◽  
Factor V ◽  
Factor Va ◽  
Dynamics Simulations ◽  
A2 Domain

Objective: The Australian snake ptFV ( Pseudonaja textilis venom-derived factor V) variant that retains cofactor function despite APC (activated protein C)-dependent proteolysis. Here, we aimed to unravel the mechanistic principles by determining the role of the absent Arg306 cleavage site that is required for the inactivation of Fva (mammalian factor Va). Approach and Results: Our findings show that in contrast to human FVa, APC-catalyzed proteolysis of ptFVa at Arg306 and Lys507 does not abrogate ptFVa cofactor function. Remarkably, the structural integrity of APC-proteolyzed ptFVa is maintained indicating that stable noncovalent interactions prevent A2-domain dissociation. Using Molecular Dynamics simulations, we uncovered key regions located in the A1 and A2 domain that may be at the basis of this remarkable characteristic. Conclusions: Taken together, we report a completely novel role for uniquely adapted regions in ptFVa that prevent A2 domain dissociation. As such, these results challenge our current understanding by which strict regulatory mechanisms control FVa activity.

Protein C Is Responsible for the Rapid Inactivation of Factor Va following Blood Clotting In Vitro

1994 ◽  
Vol 72 (01) ◽  
pp. 070-073
Author(s):  
Denise E Jackson ◽  
Christina A Mitchell ◽  
Hatem H Salem
Keyword(s):  
Protein C ◽  
Blood Clotting ◽  
Essential Role ◽  
The Other ◽  
Factor V ◽  
Factor Va ◽  
Rapid Inactivation ◽  
Protein C Activity

SummaryWhen whole blood is allowed to clot in vitro, factor V is rapidly activated to factor Va which is subsequently inactivated. We developed two monoclonal anti-protein C antibodies, one of which inhibits protein C activation and the other inhibits protein C activity. The addition of either antibody to blood before clotting in vitro significantly inhibited the inactivation of factor Va, confirming the essential role of protein C in mediating the rapid inactivation of factor Va.

Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

1999 ◽  
Vol 82 (11) ◽  
pp. 1462-1468 ◽  
Author(s):  
José Fernández ◽  
Jari Petäjä ◽  
John Griffin
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Protein C ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor V ◽  
Factor Va ◽  
Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

Simultaneous Occurrence of Human Antibodies Directed against Fibrinogen, Thrombin, and Factor V Following Exposure to Bovine Thrombin: Effects on Blood Coagulation, Protein C Activation and Platelet Function

1997 ◽  
Vol 77 (02) ◽  
pp. 343-349 ◽  
Author(s):  
Vibhuti D Chouhan ◽  
Raul A De La Cadena ◽  
Chandrasekaran Nagaswami ◽  
John W Weisel ◽  
Mehdi Kajani ◽  
...  
Keyword(s):  
Protein C ◽  
Simultaneous Occurrence ◽  
Factor V ◽  
Bovine Thrombin ◽  
Plasma Factor ◽  
Coagulation Tests ◽  
Coagulation Protein ◽  
Severe Epistaxis ◽  
Clotting Protein

SummaryWe describe a patient with severe epistaxis, prolonged coagulation tests and decreased plasma factor V following exposure to bovine topical thrombin. Patient IgG, but not normal IgG, showed binding to immobilized thrombin (bovine > human) and fibrinogen, and to factor V by Western blotting; the binding to thrombin was inhibited by hirudin fragment 54-65. Electron microscopy of rotary shadowed preparations showed complexes with IgG molecules attached near the ends of trinodular fibrinogen molecules. Patient IgG inhibited procoagulant, anticoagulant and cell-stimulating functions of thrombin demonstrated by inhibition of fibrinogen clotting, protein C activation and platelet aggregation; thrombin hydrolysis of S-2238 was not inhibited. The results suggest that the antibody is targeted against anion-binding exosite and not catalytic site of thrombin. Antifibrinogen antibodies have not been reported in patients exposed to bovine thrombin. There is a pressing need to re-evaluate the role of bovine thrombin as a therapeutic agent.

scholarly journals Factor V Is an Anticoagulant Cofactor for Activated Protein C during Inactivation of Factor Va

2009 ◽  
Vol 37 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Thomas J. Cramer ◽  
John H. Griffin ◽  
Andrew J. Gale
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V ◽  
Factor Va

Role of cations in the flocculation of Saccharomyces cerevisiae and discrimination of the corresponding proteins

1991 ◽  
Vol 37 (5) ◽  
pp. 397-403 ◽  
Author(s):  
Hiroshi Kuriyama ◽  
Itaru Umeda ◽  
Harumi Kobayashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Inhibitory Effect ◽  
Surface Proteins ◽  
Promoting Effect ◽  
Yeast Strains ◽  
Yeast Flocculation ◽  
Different Types ◽  
Anionic Groups

Asexual yeast flocculation was studied using strong flocculents of Saccharomyces cerevisiae. The inhibitory effect of cations on flocculation is considered to be caused by competition between those cations and Ca2+ at the binding site of the Ca2+-requiring protein that is involved in flocculation. Inhibition of flocculation by various cations occurred in the following order: La3+, Sr2+, Ba2+, Mn2+, Al3+, and Na+. Cations such as Mg2+, Co2+, and K+ promoted flocculation. This promoting effect may be based on the reduction of electrostatic repulsive force between cells caused by binding of these cations anionic groups present on the cell surface. In flocculation induced by these cations, trace amounts of Ca2+ excreted on the cell surface may activate the corresponding protein. The ratio of Sr2+/Ca2+ below which cells flocculated varied among strains: for strains having the FLO5 gene, it was 400 to 500; for strains having the FLO1 gene, about 150; and for two alcohol yeast strains, 40 to 50. This suggests that there are several different types of cell surface proteins involved in flocculation in different yeast strains. Key words: yeast, flocculation, protein, cation, calcium.

Anticoagulant effects of statins and their clinical implications

2014 ◽  
Vol 111 (03) ◽  
pp. 392-400 ◽  
Author(s):  
Kathleen Brummel-Ziedins ◽  
Kenneth Mann ◽  
Anetta Undas
Keyword(s):  
Factor Xiii ◽  
Observational Studies ◽  
Protein C ◽  
Thrombin Generation ◽  
Clinical Implications ◽  
Factor V ◽  
Reductase Inhibitors ◽  
Factor Va ◽  
Factor Expression ◽  
Antithrombotic Effects

SummaryThere is evidence indicating that statins (3-hydroxy-methylglutaryl coenzyme A reductase inhibitors) may produce several cholesterol-independent antithrombotic effects. In this review, we provide an update on the current understanding of the interactions between statins and blood coagulation and their potential relevance to the prevention of venous thromboembolism (VTE). Anticoagulant properties of statins reported in experimental and clinical studies involve decreased tissue factor expression resulting in reduced thrombin generation and attenuation of pro-coagulant reactions catalysed by thrombin, such as fibrinogen cleavage, factor V and factor XIII activation, as well as enhanced endothelial thrombomodulin expression, resulting in increased protein C activation and factor Va inactivation. Observational studies and one randomized trial have shown reduced VTE risk in subjects receiving statins, although their findings still generate much controversy and suggest that the most potent statin rosuvastatin exerts the largest effect.

Carbohydrate Moieties on the Procofactor Factor V, but Not the Derived Cofactor Factor Va, Regulate Its Inactivation by Activated Protein C†

Biochemistry ◽  
2002 ◽  
Vol 41 (5) ◽  
pp. 1672-1680 ◽  
Author(s):  
Jay R. Silveira ◽  
Michael Kalafatis ◽  
Paula B. Tracy
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V ◽  
Factor Va
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