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)

We recently reported that thrombin-induced platelet aggregation 1) is accompanied by cleavage of aggregin, a 100-kDa membrane protein and a putative ADP receptor, 2) is indirectly mediated by intracellularly activated calpain, and 3) requires the occupancy of high-affinity thrombin receptors. Because of the similarities between responses after platelet activation induced by thrombin and plasmin (greater than or equal to 1.0 casein unit/ml), we investigated whether or not plasmin-induced platelet aggregation proceeds by the same mechanism that underlies thrombin-induced platelet aggregation. We found that the rate of plasmin-induced aggregation of washed intact platelets and that of platelets modified by 5'-p-fluorosulfonylbenzoyladenosine (FSBA, an affinity analogue of ADP, which covalently modifies aggregin) were similar, indicating that the aggregation is independent of the ADP effect. Plasmin completely cleaved [3H]FSBA-labeled aggregin in intact platelets. A mixture of metabolic inhibitors (2-deoxy-D-glucose, gluconolactone, and antimycin A) completely inhibited plasmin-induced platelet aggregation and plasmin-induced cleavage of aggregin, demonstrating that an energy-requiring step is involved in the reaction. The synthetic hexapeptide affinity reagent Phe-Gln-Val-Val-Cys(NpyS)-Gly-NH2 (NpyS = 3-nitro-2-thiopyridine), a potent and specific inhibitor of thrombin-induced platelet aggregation and platelet calpain, completely inhibited plasmin-induced platelet aggregation and plasmin-induced cleavage of aggregin. These results suggest that, like thrombin, plasmin-induced platelet aggregation is accompanied by the cleavage of aggregin and these responses are indirectly mediated by the intracellularly activated calpain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmin-induced platelet aggregation is accompanied by cleavage of aggregin and indirectly mediated by calpain. 214 55

Plasmin was immobilized on collageno-elastic tubes (CET) using carbodiimide as the cross-linking agent. The effects of plasmin-CET grafts and corresponding soluble plasmin on fibrinogen, thrombin-mediated fibrinogen activation, and platelet activity, were investigated. There was a significant increase in fibrinogen deposition on plasmin-CETs over non-plasmin (i.e. control) CETs. Furthermore, exposure of fibrinogen to plasmin CETs enhances its deposition to control grafts situated downstream. Plasmin-bound CETs retained higher platelet deposition when preliminarily coated with fibrinogen. Finally, plasmin exerted a positive effect on thrombin-mediated fibrinogen activation at low plasmin concentrations. A mechanistic hypothesis aimed at interpreting this finding is proposed.
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PMID:Effect of soluble and immobilized plasmin on fibrinogen and platelets. 215 8

144 patients were treated with 50.000 or 100.000 fibrinolytic units (U) activator per hour over a period of up to 5 days. The drug is not yet available but in trial for the time being. We report on a survey of laboratory results in 32 of these patients. The plasminogen content of 100.000 U activator is comparable to the plasminogen content of 29 ml plasma. During activator infusion laboratory findings showed a moderate fall in plasminogen and fibrinogen. Plasmin activity was measurable during the whole period of treatment while antiplasmin was lowered considerably. There was a distinct hypocoagulabilty during activator infusion visible by a prolongation of the thrombin time and aPTT. Interestingly, no measurable activator or streptokinase activities appeared in the plasma during activator infusion. This is in contrast to findings with conventional streptokinase infusion schemes.
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PMID:Fibrinolytic treatment by infusion of streptokinase-plasminogen-complex (activator): laboratory effects. 242 24

Plasmin was acylated by reaction with benzoic acid or p-chlorobenzoic acid p'-amidinophenyl ester. Enzymatically inactive acyl-plasmin is reactivated in buffer (pH 7.5) with a half-life of 22 min (benzoyl-plasmin) and 9 min (p-chlorobenzoyl-plasmin), respectively. Plasmin is rapidly inactivated in plasma by naturally occurring plasma inhibitors so that also upon incubation of acyl-plasmin in plasma only low enzymatic activity is detectable. Following high doses of plasmin fibrinogenolysis typical of nonspecific proteolysis occurs in vivo but no fibrinolytic effects is demonstrable. On the other hand, acyl-plasmins are able either to prevent microthrombosis in the lungs induced by infusion of thrombin or to achieve repatency of the microvasculature after the onset of microthrombosis.
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PMID:[Experimental animal research on the thrombolytic effect of acyl-plasmin]. 242 95

Plasmin was immobilized on collagenous substrates using carbodiimide as a linking agent. The kinetics of soluble and immobilized plasmin were monitored by reacting them with the chromogenic substrate S-2251 (H-D-Val-Leu-Lys-pNA) in the presence and absence of a2-antiplasmin (a2-PI). The ability of immobilized plasmin to lyse synthetic clots formed from fibrinogen and thrombin was determined by detecting the formation of fibrin degradation products (FDP). The activity of immobilized plasmin was 0.02 casein units (CU)/mg of collagen. The kinetic analysis of soluble and immobilized plasmin in the presence and absence of a2-PI shows that while soluble plasmin activity was inhibited by the presence of a2-PI, the plasmin inhibitor did not interfere with the ability of immobilized plasmin to attack fibrin. In the absence of a2-PI, the ability of the immobilized plasmin to lyse synthetic clots was the same as that of soluble plasmin. In the presence of a2-PI, immobilized plasmin produced twice the amount of FDP as did soluble plasmin. The immobilized plasmin activity was stable for a period of at least 3 months.
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PMID:Enhanced in vitro fibrinolytic activity of immobilized plasmin on collagen beads. 244 Aug 93

Vascular endothelial cells (EC) play an active role in the synthesis and assembly of components of the fibrinolytic system and the generation of the major fibrinolytic protease plasmin. However, the reciprocal effects of plasmin on EC function have not been previously examined. We have studied the actions of plasmin on the production of prostacyclin (PGI2) by cultured human umbilical vein (HUVEC) and bovine aortic (BAEC) endothelial cells. Plasmin causes little or no direct stimulation of PGI2 formation by EC. Preincubation of EC with plasmin, however, produces a time- and concentration-dependent inhibition of ionophore A23187-, thrombin-, and histamine-induced PGI2 synthesis; a smaller inhibitory effect on arachidonate- and PGH2-induced PGI2 synthesis is found. Incubation of HUVEC or BAEC with a physiologic concentration of plasminogen (180 micrograms/mL) and recombinant tissue plasminogen activator (tPA) generates tPA dose-dependent plasmin activity that exceeds that generated in the absence of EC. In the presence of plasminogen, tPA also causes a tPA dose-dependent inhibition of thrombin- and ionophore A23187-stimulated PGI2 production. PGI2 inhibitory plasmin activity is generated within the concentration range of tPA achieved in plasma during pharmacologic therapy with tPA. These findings suggest that vascular endothelial cells not only regulate activation of the fibrinolytic system but may also be targets of plasmin action on PGI2 synthesis in the modulation of hemostasis and thrombosis.
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PMID:Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin. 252 69

The interaction of thrombin, plasmin or their antithrombin III complexes with isolated mouse hepatocytes was studied. Plasmin bound to hepatocytes in a concentration-dependent manner with an apparent Kd of 6.4.10(-8) M, attaining equilibrium within 10 min, and the interaction was inhibited by 6-amino-n-hexanoic acid. Plasmin treated with diisopropylfluorophosphate (DFP) bound to the cells in similar way as the untreated form of the enzyme. Thrombin bound also to hepatocytes, in a concentration-dependent manner, with a Kd of 5.4.10(-8) M reaching a steady state after 180 min. Thrombin inactivated with DFP, however, was inhibited in its binding to these cells. These data suggest that, whereas the kringle domains of plasmin are responsible for the enzyme-cell interaction, the active center of thrombin may be involved in the binding of this enzyme to hepatocytes. Plasmin-antithrombin III and thrombin-antithrombin III complexes were also associated with hepatocytes in a time-dependent manner, reaching a plateau after 180 min, and the two complexes competed in the interaction. While the interaction of active proteinases plasmin or thrombin with hepatocytes did not result in their internalization, the antithrombin III complexes were taken up by the cells, and thrombin-antithrombin III complex was degraded. These results indicate that hepatocytes may participate in the elimination of proteinase-antithrombin III complexes from the plasma, while the association of plasmin and thrombin with hepatocytes could imply distinct biological importance.
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PMID:Association of thrombin, plasmin, thrombin-antithrombin III complex and plasmin-antithrombin III complex with isolated hepatocytes. 254 38

Certain group A streptococci are known to possess a receptor for the human enzyme plasmin. Plasmin is a member of a super gene family that includes other serine proteases and kringle containing proteins. In this study we have examined the interaction of a group A streptococcus with structurally related proteins, including plasmin, glu-plasminogen, tissue plasminogen activator, kallikrein, factor XII, prothrombin, thrombin, trypsin, and urokinase. Our studies indicate that only the key fibrinolytic enzyme, plasmin, demonstrates significant binding activity to the group A streptococcus.
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PMID:Group A streptococci bind human plasmin but not other structurally related proteins. 255 Oct 62

The fibrinolytic enzyme plasmin at 0.25 units/ml produced a contraction of isolated canine basilar arteries that developed slowly and was sustained for at least 2 hours. Plasmin and thrombin (1 unit/ml) acted synergistically to enhance the contractile response. In contrast to plasmin, the marked contraction elicited by thrombin ended within 1 hour, and afterward the artery was completely tachyphylactic to thrombin. Fibrin clot, fibrinopeptides, and fibrin degradation products did not prolong significantly the effect of thrombin or prevent the tachyphylaxis. Plasmin and thrombin may occupy a common membrane receptor because exposing the artery briefly to trypsin (24 micrograms/ml) thereafter abolished the contractile effect of plasmin and thrombin without affecting the action of other agonists. Antithrombin III (1.0 unit/ml) relaxed basilar arteries that were precontracted with plasmin (0.5 unit/ml), thrombin (1.0 unit/ml), serotonin (10(-5) M), uridine triphosphate (10(-4) M), or KCl (8 X 10(-2) M). The results suggest that the vasoconstrictor effect of thrombin might contribute to hemostasis after subarachnoid hemorrhage (SAH) but, because of tachyphylaxis, not to delayed vasospasm. On the other hand, the constrictor action of plasmin might appear late in the course of SAH in association with clot lysis and tissue repair. Last, the level of the vasorelaxant antithrombin III in cerebrospinal fluid could control the appearance and severity of cerebral arterial spasm in SAH.
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PMID:Role of plasmin, thrombin, and antithrombin III as etiological factors in delayed cerebral vasospasm. 257 47

Proteasic systems are largely incriminated in tumoral invasion in breast carcinomas. They are numerous and ranged in three classes. Serine-proteinases include plasmin, elastases, thrombin and trypsine which after activation, attack some structural glycoproteins and elastin. Plasmin system is involved more in stromal invasion than in the disruption of basement membranes. Plasminogen activators do not seem to come under the influence of hormonal factors. The action of these various enzymes is limited by more or less specific anti-proteases. The activity of elastases is parallel to the abundance of elastin in the stroma. The second group is composed of cystein-proteinases. Cathepsin B has a lysosomial origin and represents the most active system. Invasive territories of mammary carcinomas contain this enzyme which can degrade collagens and activate collagenases. Metallo-proteinases with collagenases, constitute the most important proteasic system in the degradation of extra-cellular matrix. Physicochemical properties of collagenases, ionic and cellular environment condition their activity which is also enzyme dependent (activation by plasmin, cathepsin B...) Type IV collagenase activity is related to the invasive and metastatic ability of tumor cells. All these enzymatic productions are closely linked and intermittent, and moreover limited by seric and tissular anti-proteinases.
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PMID:[Proteases and breast carcinoma]. 284 88


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