Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper we studied the effect of plasma fibronectin on platelet responsiveness to low doses of thrombin or ADP. Fibronectin causes: (i) a significant lowered cytoplasmic calcium movement in platelets activated both with low doses of thrombin and with ADP, (ii) a lowered decrease of the cAMP level induced by low thrombin, but not by ADP, (iii) a dramatic decrease of protein phosphorylation in low thrombin-treated platelets. The results reported here demonstrate that plasma fibronectin behaves like an inhibitor of mild activations of human platelets; its effect is probably mediated by the glycoprotein llb-llla complex in thrombin activated platelets, whereas a different and unknown mechanism must be supposed to explain the results obtained with ADP-activated platelets.
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PMID:Fibronectin modulates the activation of human platelets. 255 59

A monoclonal antibody (A3.3) has been generated against human platelet fibronectin (FN). A3.3 reacts with human plasma FN but with no other plasma proteins. A3.3 was found to inhibit thrombin- or ionophore A23187-stimulated aggregation of gel-filtered platelets in a concentration-dependent manner in both an aggregometer assay and a sensitive well plate aggregation assay. The antibody does not block secretion of serotonin. Four other anti-FN monoclonal antibodies that recognize different epitopes on FN than A3.3 does have no effect on platelet aggregation. A3.3 does not block the adhesion of CHO cells to FN-coated surfaces, indicating that it does not bind to the identified cell-binding domain of FN. A3.3 reacts with a 160/140-kDa doublet, known to contain the cell-binding domain, that is produced by digestion of FN with elastase or thermolysin. However, the antibody does not react with lower molecular weight species that also contain the cell-binding domain or with any of the other identified domains of FN. The A3.3 epitope is extremely protease sensitive and the smallest fragment found in any digest that retains reactivity with A3.3 is a 70-kDa peptide produced in low yield by mild thermolytic cleavage of FN. These data suggest that A3.3 defines a functional site present on both the platelet and plasma FN molecule that has a direct role in platelet aggregation.
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PMID:Inhibition of platelet aggregation by a monoclonal antibody against human fibronectin. 258 28

We used flow cytometry to investigate the change of platelet membrane glycoproteins (GPIb and GP IIb/IIIa) and the distributions of fibrinogen (Fbg), thrombospondin (TSP) and fibronectin (Fn) on the surface of thrombin-stimulated platelets. The binding of a monoclonal antibody directed at the von Willebrand factor binding site on GPIb decreased in thrombin-stimulated platelets. This antibody caused a reactive delay in thrombin-induced aggregation, but had little influence on aggregability. Slight thrombin-induced aggregation was observed even after blocking the binding of Fbg to GP II b/IIIa. The new expression of GP II b/IIIa was detected on the surface of thrombin-stimulated platelets, whereas there was little increase of Fbg dependent on this GP II b/IIIa. An increase of TSP after thrombin stimulation was observed on the surface of platelets of healthy controls and patients with Glanzmann's thrombasthenia (Type I). The level of on platelet surface was slightly increased by thrombin stimulation. The mechanism involved in thrombin-induced aggregation appears to differ from that in ADP-induced aggregation.
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PMID:[Analysis of platelet surface conformation in thrombin-induced aggregation]. 258 48

Purification and partial characterization of adherence-inhibiting factor (AIF) of platelet-granule fraction in guinea pig were studied. When freshly prepared platelet-granule fraction was subjected to a gel filtration, two neutrophil adherence-inhibiting peaks, designated AIF-I (2,800 kDa) and AIF-II (12 kDa), appeared. AIF-I was sensitive to diisopropylfluorophosphate (DFP) and originated from lysosomes, whereas AIF-II was insensitive to DEP and localized in alpha-granules. Both AIFs were released from platelets by a thrombin stimulation. As the total activity of AIF-I was about 5-fold higher than that of AIF-II, AIF-I was purified and characterized. When purified AIF-I was analyzed on SDS-polyacrylamide gel electrophoresis, the 340 kDa protein band and the other large protein band were observed. Under reducing condition, AIF-I was separated into three components (340, 190 and 165 kDa). AIF-I significantly inhibited neutrophil adherence to artificial substrata and to type IV collagen-coated plastic surface, but not to fibronectin- or plasma-coated plastic surfaces, suggesting that AIF-I inhibits neutrophil adherence not only via nonspecific adsorption sites but also via type IV collagen receptors.
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PMID:Purification and partial characterization of platelet-derived adherence-inhibiting factor in guinea pig. 259 6

Human plasma fibronectin (FN) was reduced and carboxamidemethylated, and its binding ability to several matrices was analyzed in vitro. The binding of S-carboxamidemethyl (Cam)-FN to heparin-Sepharose was not influenced by either 4 M urea, 0.5 M NaCl or 0.5% heparin, but was disrupted by the coexistence of urea and NaCl or heparin. S-Cam-FN, compared with intact FN, obviously had a more potent ability to bind heparin, while it had little or no binding ability to gelatin, fibrin and thrombin-stimulated platelets. A conformational change of S-Cam-FN by heparin-binding has been proposed as a possible mechanism from the result of circular dichroic spectrum measurement.
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PMID:Enhancement of heparin-binding ability of fibronectin by S-carboxamide-methylation. 263 Jun 32

Prelining graft material with autologous functioning endothelial cells might be one of the ultimate requirements to obtain a biocompatible surface. Accordingly, endothelial cells from stripped varicose veins were enzymatically harvested and grown on a fibronectin matrix. Proliferation was investigated in defined medium supplemented with various concentrations of endothelial cell growth supplement (ECGS) (25, up to 150 micrograms/ml) and heparin (10(-8), up to 10(-5)mol/L): optimal growth required both 150 micrograms/ml of ECGS and 10(-5)mol/L heparin. Under these conditions, cell culture achieved cell densities at a confluence of 1.2 +/- 1.1 10(5) cells/cm2 with a doubling time of 1 day. During subcultivation cultured cells consistently exhibited characteristic cobblestone morphology and immunofluorescent staining for factor VIII-related antigen, whereas prostacyclin production determined by enzyme-linked immunosorbent assay for 6-keto-prostaglandin F1 alpha reached 21.1 +/- 1.2 ng/10(6) cells after 15-minute stimulation with 1 U/ml of thrombin. Heparin-containing culture medium-endothelial cell interactions were particularly studied, and with iodine 125-heparin, binding was demonstrated with an apparent dissociation constant (Kd) of 0.36 +/- 0.04 mumol/L. A cold storage technique at -80 degrees C was sought, and freezed cells were used to coat in vitro polytetrafluoroethylene grafts. Protein-treated material allowed cell attachment and growth to a confluent monolayer as assayed by light and scanning electron microscopy. These data validate the feasibility of prelining grafts in vitro with autologous functioning endothelial cells. This approach may be useful in improving the performance of small-caliber vascular grafts according to prostacyclin production and surface-bound heparin of these cells.
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PMID:Prelining of polytetrafluoroethylene grafts with cultured human endothelial cells isolated from varicose veins. 264 96

The review presents and analyzes the data available on the structure and functions of adhesive proteins, Willebrand's factor, fibrinogen, thrombospondin, and fibronectin, their secretion and interaction with blood cells and subendothelial matrix in the focus of endothelial desquamation. A structural similarity of these modular glycoproteins, their domain structure-related functions, distinctive features of cellular reception are shown. The authors also consider structural changes in platelets in their activation, rearrangement of glycoprotein complexes IIb/IIIa on the membrane for binding adhesive proteins, role of these proteins in the organization of reversible and stabilized cellular aggregates and their location in the area of the damaged endothelium. The evidence is given for one of the most important mechanisms of limiting the platelet formation-activation system of C protein, which is mediated through thrombin binding to endothelial thrombomodulin. Hemostatic abnormalities occur with congenital defects in the structure of adhesive factors or their receptors while protein deficiency in the C protein system results in formation of thromboses.
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PMID:[Morphologic and molecular aspects of the interaction of platelets with elements of the vascular wall]. 267 99

Fibronectin, von Willebrand factor, and fibrinogen each bind to the glycoprotein IIb-IIIa complex on activated platelets via an arg-gly-asp-ser (RGDS) sequence present within the adhesive proteins. Both the IIb and IIIa polypeptides of the IIb-IIIa complex on thrombin activated platelets are specifically and extensively labeled by a radiolabeled, photoactivatable arylazide derivative of the RGDS sequence when the labeling is performed in the presence of concentrations of Ca++ or Mg++ approaching 0.5 mM. In contrast, labeling of unactivated platelets, ADP activated platelets, or thrombin activated platelets in the presence of low concentrations of divalent cations resulted in restriction of labeling to the IIb polypeptide of the complex.
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PMID:Modulation of an RGDS binding site on the platelet membrane glycoprotein IIb-IIIa complex. 271 30

Addition of protease inhibitors to the culture medium has been shown to enhance neurite outgrowth by cultured mouse dorsal root ganglia (DRG). Those results are now extended to show that a diffusible source of soybean trypsin inhibitor (STI) or zones of immobilized STI can orient the direction of outgrowth towards the region of STI. However, a high concentration of diffusible STI promotes outgrowth in the opposite direction from the STI source. Immobilized leupeptin, L-lysine, or D-Phe-Pro-Arg-chloromethyl ketone can also direct outgrowth towards their immobilized areas, as do zones of laminin or fibronectin. However, derivatized zones containing urokinase or thrombin preferentially direct outgrowth away from those zones. These data support the hypothesis that a balance between extracellular protease and inhibitor is important in mediating interactions between neurite growth cone and extracellular matrix.
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PMID:Protease inhibitors influence the direction of neurite outgrowth. 271 79

If was shown that the addition of fibronectin antibodies exerted the inhibition of platelet aggregation. The tripeptide RGD inhibited the platelet aggregation induced by the same agents (ADP, epinephrine, thrombin, collagen) both in blood plasma and in suspension of washed platelets.
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PMID:[Dependence of the thrombocyte aggregation reaction on plasma fibronectin and the tripeptide arginyl-glycyl-asparagilin]. 273 79


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