On Fourier transforms of functions in $H^p(R_{+}^{n+1})$ for $p\leq 1$.

Walsh, T.

doi:10.1307/mmj/1029000953

Cited by 3 publications

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“…factor XI is activated by factor XIIa or factor XIa (autoactivation) in the presence of activated platelets or dextran sulfate (7,8,15,33), we compared these activators with thrombin to determine the preferred activator of factor XI. Fig.…”

Section: Activation Of Factor XI By Factor Xiia or Factor Xia In The mentioning

confidence: 99%

Thrombin-mediated Feedback Activation of Factor XI on the Activated Platelet Surface Is Preferred over Contact Activation by Factor XIIa or Factor XIa

Baglia¹,

Walsh²

2000

Journal of Biological Chemistry

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To study the pathways for initiation of intrinsic blood coagulation, activated human platelets were compared with dextran sulfate as surfaces for factor XI activation by factor XIIa, factor XIa, or thrombin. Activated gelfiltered platelets promoted the activation of factor XI (60 nM) by thrombin (0.02-10 nM, EC 50 ϳ100 pM, threshold concentration ϳ10 pM) at initial rates 2-to 3-fold greater than those obtained with dextran sulfate in the presence of either high molecular weight kininogen (45 nM) and ZnCl 2 (25 M) or prothrombin (1.2 M) and CaCl 2 (2 mM). The maximum rates of factor XI activation achieved in the presence of activated gel-filtered platelets were 30 nM⅐min ؊1 with thrombin, 6 nM⅐min ؊1 with factor XIIa and 2 nM⅐min ؊1 with factor XIa. Values of turnover number calculated at various enzyme concentrations (0.05-1 nM) were 24 -167 (mean ‫؍‬ 86) min ؊1 for thrombin, 4.6 -50 (mean ‫؍‬ 21) min ؊1 for factor XIIa, and 1.3-14 (mean ‫؍‬ 8) min ؊1 for factor XIa. A physiological concentration of fibrinogen (9.0 M) inhibited factor XI activation by thrombin (but not by factor XIIa) in the presence of dextran sulfate but not in the presence of gel-filtered platelets. Compared with factors XIIa and XIa, thrombin is the preferred factor XI activator, and activated platelets are a relevant physiological surface for thrombinmediated initiation of intrinsic coagulation in vivo.Human coagulation factor XI is a disulfide-linked homodimer consisting of two identical polypeptide chains each containing 607 amino acids. Factor XI is present in human plasma as a zymogen that requires proteolytic activation to develop serine protease activity (1-5). It circulates in human plasma in a noncovalent complex with high molecular weight kininogen (HK) 1 (6) and can be activated by three biologically relevant proteases: factor XIIa, factor XIa, and thrombin (1,7,8). The primary structure of factor XI has been determined (9, 10), including the identification of four tandem repeat sequences, designated Apple (A1, A2, A3, and A4) domains in the heavy chain region of factor XI. Binding sites (11-15) for thrombin, the Kringle 2 domain of prothrombin, and HK are present in the A1 domain, whereas both heparin-and plateletbinding sites exist within the A3 domain (16 -18) and a binding site for factor XIIa is located in the A4 domain (19).Factor XI can participate in the contact phase of blood coagulation in a reaction that requires the presence of anionic surfaces for optimal activation in vitro by factor XIIa (6,[20][21][22]. However, deficiencies in factor XII, prekallikrein, and HK are not associated with hemostatic abnormalities, whereas a deficiency in factor XI produces abnormal bleeding complications (23-25). Therefore, it has been suggested that the physiologically relevant pathway for factor XI activation might constitute feedback activation either by thrombin or by factor XIa (7,8,15). All three proteases cleave each monomer of factor XI at the Arg 369 -Ile 370 bond generating the new amino-terminal sequence (IVGG) of the cataly...

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Section: Activation Of Factor XI By Factor Xiia or Factor Xia In The mentioning

confidence: 99%

Thrombin-mediated Feedback Activation of Factor XI on the Activated Platelet Surface Is Preferred over Contact Activation by Factor XIIa or Factor XIa

Baglia¹,

Walsh²

2000

Journal of Biological Chemistry

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“…The zymogen FXI can bind to receptors (2)(3)(4), consisting of the glycoprotein Ib-IX-V complex (5) on the plasma membranes of activated human platelets, where it can be incorporated into platelet membrane microdomains (i.e. lipid rafts) (6) for efficient activation by thrombin or by FXIIa (7)(8)(9)(10). The resulting enzyme, FXIa, can then activate the vitamin K-dependent protein, FIX, to initiate the consolidation phase of blood coagulation (1).…”

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confidence: 99%

Structural and Mutational Analyses of the Molecular Interactions between the Catalytic Domain of Factor XIa and the Kunitz Protease Inhibitor Domain of Protease Nexin 2

Navaneetham

Jin²,

Pandey³

et al. 2005

Journal of Biological Chemistry

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Factor XIa (FXIa) is a serine protease important for initiating the intrinsic pathway of blood coagulation. Protease nexin 2 (PN2) is a Kunitz-type protease inhibitor secreted by activated platelets and a physiologically important inhibitor of FXIa. Inhibition of FXIa by PN2 requires interactions between the two proteins that are confined to the catalytic domain of the enzyme and the Kunitz protease inhibitor (KPI) domain of PN2. Recombinant PN2KPI and a mutant form of the FXI catalytic domain (FXIac) were expressed in yeast, purified to homogeneity, co-crystallized, and the structure of the complex was solved at 2.6 Å (Protein Data Bank code 1ZJD). In this complex, PN2KPI has a characteristic, disulfide-stabilized double loop structure that fits into the FXIac active site. To determine the contributions of residues within PN2KPI to its inhibitory activity, selected point mutations in PN2KPI Coagulation factor XI (FXI) 4 is a unique homodimeric coagulation protein, present in human plasma at a concentration of ϳ30 nM, that is essential for normal hemostasis, as evidenced by the fact that FXI deficiency is associated with a hemorrhagic disorder (1). The zymogen FXI can bind to receptors (2-4), consisting of the glycoprotein Ib-IX-V complex (5) on the plasma membranes of activated human platelets, where it can be incorporated into platelet membrane microdomains (i.e. lipid rafts) (6) for efficient activation by thrombin or by FXIIa (7-10). The resulting enzyme, FXIa, can then activate the vitamin K-dependent protein, FIX, to initiate the consolidation phase of blood coagulation (1).A variety of important control mechanisms exist for regulating the activity of coagulation proteases in plasma. Several members of the serpin family have been proposed as physiological regulators of FXIa activity in plasma, including C1 inhibitor (11, 12), ␣-1-protease inhibitor (13, 14), antithrombin III (15), ␣-2-antiplasmin (16), and protease nexin 1 (17). However, a platelet secretory protein and member of the class of Kunitz-type inhibitors, protease nexin 2 (PN2), has recently been shown to be a much more potent and physiologically relevant FXIa inhibitor based on detailed kinetics studies (18 -23). PN2 is a ϳ120-kDa isoform of the Alzheimer ␤-amyloid protein precursor (APP) that contains a Kunitz-type serine protease inhibitor (PN2KPI) domain (22). Platelets are an important source of several isoforms of APP, including the APP 751 isoform of PN2 (23, 24). Full-length APP is membraneassociated (25) and is processed by proteases in platelets (26, 27). Upon platelet activation by physiological stimulators, PN2 is secreted from ␣-granules into plasma and inhibits FXIa (22-24), suggesting a role for this protein in blood coagulation. PN2 is a slow, tight binding inhibitor of FXIa with K i of ϳ300 -500 pM (18,20,22). The KPI domain of PN2 is 57 amino acids in length (Glu 289 -Ile 345 in the 751-amino acid isoform of PN2) and is known to contain the entire FXIa inhibitory function of PN2 (19 -21, 28). Similarly, all of the information r...

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“…Platelets stimulated by ADP and collagen stimulate clotting ability and fragmentation, as well as proteolysis of factor XI by a mechanism independent of HF [6,7]. Intact platelets possess the same property, although weaker [7].…”

Section: Resultsmentioning

confidence: 99%

“…

We know, in particular, that purified HF can be activated by platelets stimulated by ADP and collagen, and also that platelet factor 4 prevents contact activation of HF [7,8].

…”

mentioning

confidence: 99%

“…The role of platelets, structurally and functionally the most labile blood cells, carrying both HF itself [3,4] on their surface and also a number of specific proteins which participate in activation of the blood clotting system, is particularly important in this respect.We know, in particular, that purified HF can be activated by platelets stimulated by ADP and collagen, and also that platelet factor 4 prevents contact activation of HF [7,8]. The character of the activating principle is one of the key factors in the biochemical mechanism of regulation of KKS, linked functionally with clotting and fibrinolysis sytems [i].…”

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confidence: 99%

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Importance of number and shape of platelets for contact activation of the blood kallikrein-kinin systemin vitro

Krizhevskaya¹,

Гомазков²,

Ionov³

et al. 1984

Bull Exp Biol Med

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Activation of Hageman factor (HF) on contact with artificial surfaces is a widely used model for the investigation of the blood kallikrein--kinin system (KKS).It has been shown that activation of HP systems in the micricirculation can be mediated by proteinases or functionally modified blood and endothelial cell membranes [6,7,9]. The role of platelets, structurally and functionally the most labile blood cells, carrying both HF itself [3,4] on their surface and also a number of specific proteins which participate in activation of the blood clotting system, is particularly important in this respect.We know, in particular, that purified HF can be activated by platelets stimulated by ADP and collagen, and also that platelet factor 4 prevents contact activation of HF [7,8]. The character of the activating principle is one of the key factors in the biochemical mechanism of regulation of KKS, linked functionally with clotting and fibrinolysis sytems [i].The role of number and shape of platelets for contact activation of KKS was investigated. The main aim was an attempt to separate the plasma (biochemical) and cellular (membrane) components of activation of this system. EXPERIMENTAL METHODMale Wistar rats weighing 180-300 g, kept on a standard diet, were used.To obtain the different platelet f~actions, citrated blood (1:9), obtained from the right ventricle of animals anesthetized with pentabarbital, was used.The principal fraction containing platelets (i) was obtained by centrifugation of citrated blood at 1500 rpm for i0 min.This fraction contained from 5"i0 s to 3"10 ~ cells in 1 ~i. To obtain platelet-free plasma (2), fraction 1 was recentrifuged at 7000 rpm.This fraction contained from 0 to 25,000 cells/ml. Next, to obtain "washed" platelets the residue was washed with Tyrode solution not containing calcium or magnesium ions. Cells obtained from 2 ml of fraction 1 were resuspended in 0.5 ml of Tyrode solution.All the procedures indicated above were undertaken at room temperature, using plastic and siliconized vessels. The "washed" platelets were frozen and thawed 5 times, using dry ice.In this way up to 95% of the cells were disintegrated. The suspension of disintegrated platelets was ultracentrifuged at i00,000 g for 20 min.The supernatant fraction, into which the soluble contents of the platelets has passed, was used; the membrane fraction was resuspended in Tyrode solution.This fraction contained the disintegrated bodies of the platelets, their fragments, and fragments of membranes.The initial arginine esterase activity and the prekallikrein (PKK) level in the blood plasma were determined by the method in [2], using TAME (N-a-tosyl-L-arginine methyl ester, from Reanal, Hungary) as the substrate. The composition of the incubation mixture was changed depending on the series of the investigation, but the conditions of determination on the whole (ratio of the components, conditions of incubation, quantity of added reagents, etc.) always corresponded to the method indicated above. The shape of the nature and modified...

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On Fourier transforms of functions in $H^p(R_{+}^{n+1})$ for $p\leq 1$.

Cited by 3 publications

References 0 publications

Thrombin-mediated Feedback Activation of Factor XI on the Activated Platelet Surface Is Preferred over Contact Activation by Factor XIIa or Factor XIa

Thrombin-mediated Feedback Activation of Factor XI on the Activated Platelet Surface Is Preferred over Contact Activation by Factor XIIa or Factor XIa

Structural and Mutational Analyses of the Molecular Interactions between the Catalytic Domain of Factor XIa and the Kunitz Protease Inhibitor Domain of Protease Nexin 2

Importance of number and shape of platelets for contact activation of the blood kallikrein-kinin systemin vitro

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