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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has previously been shown, that large differences exist between the effects of 6-aminohexanoic acid or alpha1-antitrypsin on fibrinolysis caused by a porcine tissue plasminogen activator or by human urokinase, while insignificant differences exist between the effects of a number of natural protease inhibitors on fibrinolysis caused by the two types of plasminogen activator. The present study shows that changes in substrate composition (pH, ionic strength fibrinogen concentration, plasminogen concentration) may influence to different degrees the fibrinolytic activities of human urokinase and the porcine tissue plasminogen activator. It is suggested, that this finding is partly related to marked differences in affinity for fibrin of the two activators.
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PMID:Differences in the reactivities of human urokinase and the porcine tissue plasminogen activator. 1 58

A plasminogen activator secreted by cultured human pancreatic carcinoma (Mia PaCa-2) cells has been purified to apparent homogeneity by procedures including Sepharose-L-arginine methyl ester affinity chromatography, Sephadex G-200 gel filtration, isoelectric focusing, and sodium dodecyl sulfate gel electrophoresis. The plasminogen activator shares many properties with urokinase including: molecular weight (55 000), isoelectric point (8.7), heat stability (60 degrees C, 30 min), PH stability (1.5-10), and its mode of activation of plasminogen. The intracellular enzyme is membrane bound and can be solubilized by detergent. Solubilized activator has a molecular weight similar to that of the secreted enzyme as determined by sodium dodecyl sulfate gel electrophoresis. The production of plasminogen activator by Mia PaCa-2 cells is totally inhibited by actinomycin D and cycloheximide.
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PMID:Purification and characterization of a plasminogen activator secreted by cultured human pancreatic carcinoma cells. 1 90

The major plasmin inhibitors namely alpha2-plasmin inhibitor and alpha2-macroglobulin were compared for their effects on lysis of fibrin clot. Plasmin fibrinolytic activity was immediately inhibited by alpha2-plasmin inhibitor, whereas alpha2-macroglobulin inhibited plasmin progressively. Urokinase(plasminogen activator)-induced clot lysis was inhibited efficiently by alpha2-plasmin inhibitor present in the clot. Inhibition of urokinase-induced clot lysis by alpha2-macroglobulin was weak and the molar concentration necessary for alpha2-macroglobulin to achieve the same degree of inhibition as that achieved with alpha2-plasmin inhibitor was about 10 times higher than that of alpha2-plasmin inhibitor. Binding of Lys-plasminogen to fibrin was inhibited by alpha2-plasmin inhibitor but not by alpha2-macroglobulin. Molar concentrations of alpha2-plasmin inhibitor which were effective in inhibiting the binding were 30 times less than that of 6-aminohexanoicacid. alpha2-Plasmin inhibitor was found to interact with Lys-plasminogen to form a weakly-bound complex which is dissociable in the presence of 6-aminohexanoic acid, suggesting that inhibition of binding of Lys-plasminogen to fibrin by alpha2-plasmin inhibitor may be due to interaction of alpha2-plasmin inhibitor with a specific site of the plasminogen molecule and that the site may be 6-aminohexanoic acid-binding site. It is suggested that alpha2-plasmin inhibitor is more reactive and efficient inhibitor of fibrinolysis than alpha 2-macroglobulin.
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PMID:Effects of alpha2-plasmin inhibitor on fibrin clot lysis. Its comparison with alpha2-macroglobulin. 7 50

By the immunofluorescence technique, fibrin, plasminogen and alpha2-macroglobulin demonstrated a similar basic pattern of distribution in the artificial thrombi, rimming the platelet aggregates in the white part and forming a network structure in the red part. The content of plasminogen seemed to be higher in the red part than in the white part. After superfusion with urokinase solution, urokinase was found in a similar pattern of distribution of that of fibrin. The content of urokinase seemed to be higher in the red part, especially in its outer area, than in the white part. It is concluded that urokinase diffused into the artificial thrombi can convert plasminogen, trapped onto fibrin in threads to plasmin. Poor lysibility of the white part might be due to thick strands of fibrin, a low content of plasminogen and a low diffusibility of plasminogen activator, in addition to the antifibrinolytic activity of platelets.
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PMID:Immunofluorescence study on thrombolysis with special reference to the patterns of distribution and the contents of fibrin, plasminogen, alpha2-macroglobulin and urokinase in artificial thrombi. 7 51

The plasminogen activator of the arterial wall was studied with the histochemical method of TODD. The plasminogen activator was removed from the sections after extraction with M-potassium thiocyanate. By this procedure we suggest that the activator demonstrated by the histochemical method is the same substance as that prepared by the extraction method with thiocyanate of ASTRUP and STAGE. However, a new fibrinolytic activity was restored after treatment of these extracted sections with streptokinase or urokinase. There were no differences in the different types of arteries examined and normal or atherosclerotic arteries. Similar findings were found when kidney or myocardial tissues were examined. It is suggested that the arterial and other tissues contain proactivator-plasminogen which is not extracted from the tissue by potassium thiocyanate and can adsorb streptokinase or urokinase.
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PMID:On the nature of fibrinolytic activity of arteries. 7 13

Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.
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PMID:Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery. 9 90

The assay of plasminogen activator activities on fibrin plates was re-evaluated with special reference to fibrinolysis inhibitors present in samples and in fibrin plates. The nature, action and stability of inhibiting material were studied in tissue with considerable differences in activator and inhibitor contents: human lung, liver and placenta. Extracts were tested for inhibitory capacity against purified human uterine tissue plasminogen activator, urokinase and plasmin of fibrin plates prepared from different grades of fibrinogen and fibrin. The tissue extracts inhibited fibrinolysis on fibrin plates to varying degrees, dependent on the sample medium, the type of fibrin plate and the kind of plasminogen activator. The influence of inhibitors in the sample and in the fibrin plate was partly abolished by the presence of 2 M KSCN in the sample. The procedure for preparing the samples as described by Astrup and Albrechtsen did not completely eliminate the inhibitory action against the added plasminogen activators. Comparison of urokinase inhibition with tissue activator inhibition by the tissue extracts as to the degree of denaturation in the Astrup and Albrechtsen procedure showed that they have much in common. Nevertheless, some differences were found which indicated the possible existence of separate urokinase and tissue activator inhibitors or of different inhibition mechanisms for these plasminogen activators.
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PMID:Interfering factors in the assay of plasminogen activators by the fibrin plate method. Occurrence of different inhibitors against tissue plasminogen activator and urokinase. 11 68

The binding specificities of human urinary urokinase (EC 3.4.99.26) and HeLa cell plasminogen activator were studied using peptidyl chloromethyl ketone inhibitors. A 125I-labeled fibrin assay has been developed to yield kinetic information. Reagents of the sequence X-Gly-ArgCH2Cl were the most effective. The susceptibility of the HeLa cell plasminogen activator differed from that of urokinase in several respects indicating the utility of this type of inhibitor in distinguishing between proteases of this specificity.
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PMID:Inactivation of the plasminogen activator from HeLa cells by peptides of arginine chloromethyl ketone. 11 16

Three types of plasminogen activator could be distinguished in extracts from human uterine tissue. The activators differed in thermostability or in mode of inhibition by EACA. All the extracts contained stable as well as labile activators. The saline extracts were uniformly inhibited by increasing concentrations of EACA. Extracts made with 2 M ammonium thiocyanate were either uniformly inhibited by EACA or showed deflections indicating contamination with an activator, which was inhibited in a biphasic manner. It was possible to distinguish between: (1) An activator, abundantly present in the tissue, which was uniformly inhibited and stable. (2) Another uniformly inhibited activator, which was labile. (3) An activator, inhibited in a biphasic manner, similar to urokinase, which was present in varying amounts in uteri with the endometrium in the proliferative phase. Gel filtration of the uterine extracts showed two major activity peaks corresponding to particle sizes of 60,000 dalton and about 10,000 dalton. Antiserum to purified plasminogen activator, prepared from porcine ovaries, inhibited the activity of the human uterine extracts, but not the activities of human urokinase or urine. Urokinase antiserum in a concentration completely inhibiting human urine or urokinase, inhibited only 10% or less of the activities of human uterine extracts.
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PMID:Separation of plasminogen activators from human uterine tissue and a comparison with activators from human urine and porcine tissue. 11 1

The decrease of tumorigenicity by mouse melanoma clone B559 after growth in the presence of 5-bromodeoxyuridine (BrdU) has been correlated with a decrease in detectable cellular plasminogen activator. Reduction of both activities occurs after one to two cell divisions in the presence of this thymidine analog and is virtually complete within three to four cell cycles. These changes are fully reversible; four to five cell divisions in the absence of BrdU are sufficient to allow both tumorigenicity and plasminogen activator levels to return to normal. These results support the hypotheses that (a) the expression of a cellular plasminogen activator is closely associated with the transformation of normal to malignant cells and that (b) the suppression of tumorigenicity by BrdU reflects the capacity of this base analog to inhibit the expression of specialized functions which accompany the malignant state.
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PMID:Correlated suppression by 5-bromodeoxyuridine of tumorigenicity and plasminogen activator in mouse melanoma cells. 12 36


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