Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLASMINOGEN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1992

Comparison of the thrombolytic activity of the novel plasminogen activator, LY210825, to anisoylated plasminogen-streptokinase activator complex in a canine model of coronary artery thrombolysis.

We have compared the thrombolytic efficacy of a novel single-chain, recombinant tissue-type plasminogen activator variant, LY210825, containing the second kringle and serine protease domains of native tissue-type plasminogen activator, with anisoylated plasminogen-streptokinase activator complex (APSAC). Male hounds (16-22 kg) were anesthetized, the left circumflex coronary artery was isolated and an electromagnetic flow probe was placed around the artery proximal to the first main branch for the measurement of coronary blood flow. An occlusive thrombus was formed after electrolytic injury of the intima of the coronary artery. After an occlusion period of 1 hr, either LY210825 (n = 8) or APSAC (n = 6) was administered as a single i.v. injection of 0.45 mg/kg. Blood was drawn (3.8% citrate) for determination of plasma fibrinogen, plasminogen and alpha-2 antiplasmin. Time to reperfusion was significantly faster with LY210825 than with APSAC, 20 +/- 2 vs. 54 +/- 8 min, respectively. The incidence of reocclusion was similar for both agents. APSAC produced significant depletion of alpha-2 antiplasmin, plasminogen and circulating fibrinogen, whereas LY210825 caused only slight consumption of plasminogen and only small decreases in fibrinogen. After a single injection of LY210825, thrombolytic concentrations of plasminogen activator were available immediately, whereas there was a significant delay in lytic concentrations of active streptokinase-plasmin complex. Consequently, LY210825 reperfused the coronary artery faster than did APSAC. In addition, LY210825 spared plasma fibrinogen, plasminogen and alpha-2 antiplasmin and therefore, could potentially minimize the risk of bleeding complications.

Animals↗
PubMed1985

Species specificity in the acceleration of tissue-type plasminogen activator-mediated activation of plasminogens, by fibrinogen cyanogen bromide fragments.

Activation of human plasminogen by human tissue-type plasminogen activator (t-PA) is accelerated in the presence of cyanogen bromide digests of human fibrin(ogen). In the present study a possible species specificity of this phenomenon was investigated. All combinations of the plasminogens, fibrin monomers and cyanogen bromide digests of the fibrinogens of man, pig, rat, cat and monkey (Macaca mulatta), and three t-PA species (man, rat and pig) were studied. No species differences were noted with the fibrin monomers i.e. the activation rate of all five plasminogens increased more than 20-fold in the presence of all five fibrin monomer species, irrespective if man, rat or pig t-PA was used. However, we found that species specificities come to expression when cyanogen bromide digests of the corresponding fibrinogens were used as accelerators. Our results indicate that the plasminogen species and not the source of t-PA or fibrinogen dictates if accelerated activation occurs in the presence of a fibrinogen CNBr digest. The plasminogens can be roughly divided in two groups: --One group, comprising human, monkey and cat plasminogen, which are activated at a higher rate by all three t-PA species in the presence of fibrinogen digest independent on the fibrinogen species from which the digest was prepared. --Another group, comprising pig and rat plasminogen, which is not or only marginally more quickly activated by the 3 t-PA species, irrespective of the fibrinogen species from which the CNBr digest was prepared.

Animals↗
PubMed1990

On the molecular interactions between fibrin, tissue-type plasminogen activator and plasminogen.

The molecular interactions involved in the fibrin-mediated stimulation of plasminogen activation by tissue-type plasminogen activator (t-PA) were studied using natural human plasminogen (nPlg) and rPlg-Ala740, a recombinant human plasminogen in which the catalytic site is destroyed by mutagenesis of the active site Ser740 to Ala. Using this rPlg-Ala740 moiety, the dissociation constant of the interaction between plasminogen and CNBr-digested fibrinogen was determined to be 0.40 microM. In addition, conversion of 125I-labeled single chain plasminogen to two chain plasmin by single chain recombinant t-PA (rt-PA) in the absence or the presence of CNBr-digested fibrinogen was quantitated on reduced SDS-gel electrophoresis, combined with autoradiography and radioisotope counting of gel bands. In the absence of fibrin, the activation rate of nPlg and rPlg-Ala740 by single-chain rt-PA was comparable. In the presence of fibrin, however, the activation rate of rPlg-Ala740 was about 20-fold lower than that of nPlg. These results with rPlg-Ala740 may be explained by an impaired formation of the stable cyclic ternary complex between plasminogen, t-PA and fibrin, which mediates the fibrin stimulation of plasminogen activation by t-PA or, alternatively, by impaired conversion of single chain rt-PA to two chain rt-PA at the fibrin surface.

Animals↗
PubMed1982

Studies on the kinetics of plasminogen activation by tissue plasminogen activator.

The steady-state rate of plasminogen activation by tissue plasminogen activator has been determined at various plasminogen concentrations. A plasmin substrate method similar to that presented by Christensen and Müllertz (Biochim. Biophys. Acta 480 (1977) 257-281) was used. The reaction was studied using one-chain type and two-chain type tissue plasminogen activator, N-terminal glutamic acid and N-terminal lysine plasminogen in the presence and in the absence of fibrin (eight studies). The kinetic data were fitted to a general Wong-Hanes equation and the simplest equation with significant parameters was found. In the absence of fibrin N-terminal glutamic acid plasminogen activation obeyed the Michaelis-Menten rate equation (Km 4.9 and 7.6 micro M and kcat 0.0013 and 0.0078 s-1 for one-chain type and two-chain type tissue plasminogen activator, respectively. In the absence of fibrin the activation of N-terminal lysine plasminogen activation failed to obey the Michaelis-Menten rate equation. Fibrin was found to stimulate greatly (up to 1000-fold) the steady-state activation rate. A theory for the fibrin stimulating mechanism is presented.

Animals↗
PubMed1985

Retinoids and synovial factor(s) stimulate the production of plasminogen activator by cultured human chondrocytes. A possible role for plasminogen activator in the resorption of cartilage in vitro.

Agents such as retinol, interleukin 1 and catabolin stimulate resorption of cultured cartilage. This process seems to be mediated by chondrocytes, but the mechanism by which breakdown occurs remains unknown. We have found that (10(-6)-10(-8) M) retinoic acid and (1 X 10(-6) M) retinol, in the presence or absence of a factor derived from cultured synovium (synovial factor), stimulate the degradation of fibrin by human chondrocytes in culture. Plasminogen was required for the enhancement of fibrinolysis, suggesting that the breakdown depended upon the production of plasminogen activators and subsequent liberation of plasmin. However, the chondrocytes did not release significant amounts of plasminogen activator, and the effects of the synovial factor and retinoids resulted from augmentation of the production or activity of enzymes which remained bound to the cell layer. The role of plasminogen in the resorption of cultured cartilage was also investigated. In the presence of plasminogen, (1 X 10(-8) M) retinoic acid or synovial factor stimulated the breakdown of cultured bovine nasal cartilage, but in the absence of plasminogen, the effect of synovial factor was abolished and that of retinoic acid reduced. However, in cultures containing both retinoic acid and synovial factor the resorption process was not affected by removal of plasminogen. Thus, the resorption of cartilage matrix in vitro may be partially mediated by plasminogen activators and plasmin.

Animals↗
PubMed2000

Plasminogen and tissue plasminogen activator interact with antithrombin III.

Human antithrombin III was demonstrated to bind plasminogen specifically in a time and concentration-dependent manner. The above binding was also confirmed using ligand western blot assays. The interaction of plasminogen was significantly (>90%) inhibited by lysine, indicating the involvement of kringles in binding antithrombin III. Plasminogen also bound to heparin-antithrombin III complex. In converse experiments, antithrombin III also interacted with immobilized plasminogen. Using carboxypeptidase B digestion, the plasminogen-binding site of antithrombin III was localized to the carboxy-terminus lysine of the anticoagulant protein. Tissue plasminogen activator also interacted with antithrombin III in a time- and concentration-dependent manner and its binding was also significantly (>90%) inhibited by lysine. Moreover, the interaction of plasminogen and tissue plasminogen activator with antithrombin III was competitive. These results provide the first evidence for the interaction of antithrombin III with fibrinolytic factors and suggest that antithrombin III may serve to localize these factors at the site of clot formation.

Antithrombin III↗
PubMed2005

Plasminogen detection in oocytes and plasminogen activator activities in the porcine oviduct during the estrous cycle.

Plasminogen activators (PAs) are highly specific serine proteases that convert the extracellular zymogen plasminogen into the active proteinase plasmin. Plasminogen-dependent proteolytic activity was detected by zymography both in the tissue membrane fraction of oviducts and in the oviductal flushing obtained at the preovulatory (Pre-Ov), postovulatory (Post-Ov) and mid-luteal (Mid-L) stages of the estrous cycle. A main proteolytic band, with a relative mobility similar to a human melanoma cell tissue-type plasminogen activator (t-PA), was found in all samples. Two additional components were observed in Pre-Ov and Post-Ov oviductal flushing but not in the tissue membrane fraction. In the oviductal flushing the PA activity was significantly higher in the Post-Ov stage than in the Pre-Ov one. Both urokinase-type plasminogen activator (u-PA, 50 kDa) and t-PA (72 kDa) were detected by Western blot; they showed differences in their relative concentration between Post-Ov and Pre-Ov oviductal flushing. The main PA substrate, plasminogen, was detected by indirect immunofluorescence in the cumulus cell extracellular matrix (ECM) and oocyte zona pellucida (ZP). In denuded oocytes, plasminogen was also detected on the surface of the plasma membrane. It is possible that oviductal PAs may act on the plasminogen present in the cumulus cell ECM and ZP; consequently, the generated plasmin could be involved in the rebuilding or degradation of these oocyte structures during fertilization or early development.

Animals↗
PubMed1993

Mycoplasma cells stimulate in vitro activation of plasminogen by purified tissue-type plasminogen activator.

In an in vitro direct assay with tissue-type plasminogen activator (tPA), plasminogen and the chromogenic substrate S-2251, the ability of Mycoplasma fermentans KL4 to stimulate tPA-mediated activation of plasminogen to plasmin was studied. Mycoplasma cells markedly enhanced the activation of plasminogen by tPA in a concentration-, temperature- and pH-dependent manner. Nonidet P-40 (0.01%), sonication, and freezing and thawing of the cells substantially increased the stimulatory effect of mycoplasma on tPA activity. In contrast, the activation of plasminogen by urokinase was refractory to mycoplasma cells. The mycoplasma-mediated stimulation of tPA activity was prevented by epsilon-aminocaproic acid (EACA), a lysine analogue known to block lysine-binding sites (LBS) in plasminogen and tPA. Among several Mycoplasma fermentans strains tested, incognitus strain demonstrated the highest stimulation activity. These results suggest that mycoplasma cells interact with LBS in tPA and plasminogen to enhance plasminogen activation.

Enzyme Activation↗
PubMed1997

Streptococcus uberis acquires plasmin activity following growth in the presence of bovine plasminogen through the action of its specific plasminogen activator.

Three (0140J, C197C and EF20) out of four strains of Streptococcus uberis exhibited high levels of bound plasmin activity following growth in the presence of bovine plasminogen. The remaining strain (C197) bound considerably less plasmin following growth in the same medium. In contrast to the others, this strain was unable to activate bovine plasminogen. Following growth of strain C197 in the presence of bovine plasminogen and a source of plasminogen activator (urokinase or culture filtrate from strain 0140J) high levels of bacterially associated plasmin were detected. None of the strains was able to activate human plasminogen and only trace levels of plasmin activity were detected in association with the S. uberis following growth in the presence of human plasminogen. All strains were able to bind plasmin activity following incubation in the presence of either bovine or human plasmin. However, in each case the level of activity detected following incubation in human plasmin was approximately five-fold less than that observed following incubation with bovine plasmin. None of the strains bound detectable levels of either human or bovine plasminogen. It is concluded that activation of plasminogen is required prior to binding of plasmin by S. uberis.

Animals↗
PubMed1985

Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor.

Fibrinolytic components after venous occlusion and concentrations of tissue plasminogen activator inhibitor were studied in 100 consecutive patients with confirmed recurrent deep vein thrombosis or pulmonary embolism. After 20 minutes of venous occlusion the fibrinolytic response was decreased in 33 patients, as measured both amidolytically with S-2251 and on fibrin plates. Two different mechanisms responsible for the poor fibrinolytic response could be distinguished. Twenty two of the patients in whom the response was poor released normal amounts of tissue plasminogen activator antigen, as assayed by immunoradiometric assay, but had appreciably increased concentrations of tissue plasminogen activator inhibitor. The 11 other patients in whom the response was poor had both low tissue plasminogen activator activities and low tissue plasminogen activator antigen concentrations but normal concentrations of tissue plasminogen activator inhibitor. The results show not only that defective synthesis or release of tissue plasminogen activator may be important in the pathogenesis of venous thrombosis but also that a large group of patients with thrombosis have an increased concentration of the inhibitor to tissue plasminogen activator.

Adolescent↗
PubMed1992

Vampire bat salivary plasminogen activator exhibits a strict and fastidious requirement for polymeric fibrin as its cofactor, unlike human tissue-type plasminogen activator. A kinetic analysis.

The vampire bat salivary plasminogen activator (BatPA) is virtually inactive toward Glu-plasminogen in the absence of a fibrin-like cofactor, unlike human tissue-type plasminogen activator (tPA) (the kcat/Km values were 4 and 470 M-1 s-1, respectively). In the presence of fibrin II, tPA and BatPA activated Glu-plasminogen with comparable catalytic efficiencies (158,000 and 174,000 M-1 s-1, respectively). BatPA's cofactor requirement was partially satisfied by polymeric fibrin I (54,000 M-1 s-1), but monomeric fibrin I was virtually ineffective (970 M-1 s-1). By comparison, a variety of monomeric and polymeric fibrin-like species markedly enhanced tPA-mediated activation of Glu-plasminogen. Fragment X polymer was 2-fold better but 9-fold worse as cofactor for tPA and BatPA, respectively, relative to fibrin II. Fibrinogen, devoid of plasminogen, was a 10-fold better cofactor for tPA than fibrinogen rigorously depleted of plasminogen, Factor XIII, and fibronectin; the enhanced stimulatory effect of the less-purified fibrinogen was apparently due to the presence of Factor XIII. By contrast, the two fibrinogen preparations were equally poor cofactors of BatPA-mediated activation of Glu-plasminogen. BatPA possessed only 23 and 4% of the catalytic efficiencies of tPA and two-chain tPA, respectively, in hydrolyzing the chromogenic substrate Spectrozyme tPA. However in the presence of fibrin II, BatPA and tPA exhibited similar kcat/Km values for the hydrolysis of Spectrozyme tPA. Our data revealed that BatPA, unlike tPA, displayed a strict and fastidious requirement for polymeric fibrin I or II. Consequently, BatPA may preferentially promote plasmin generation during a narrow temporal window of fibrin formation and dissolution.

Animals↗
PubMed1992

von Willebrand factor antigen, tissue-type plasminogen activator antigen, and risk of death in human immunodeficiency virus 1-related clinical disease: independent prognostic relevance of tissue-type plasminogen activator.

Tissue-type plasminogen activator, von Willebrand factor, and plasminogen-activator inhibitor type 1 plasma levels were measured at first consultation in 85 consecutive patients infected with human immunodeficiency virus. Patients were assigned to three groups according to clinical status: mild disease group, intermediate group, and acquired immunodeficiency syndrome group. Significant differences were found in von Willebrand factor, tissue-type plasminogen activator, and plasminogen-activator inhibitor type 1 plasma levels among the three groups: severe clinical status was associated with higher von Willebrand factor, tissue-type plasminogen activator, and plasminogen-activator inhibitor type 1 plasma levels. Significant correlations were found among these three parameters, such known biologic prognostic indicators of human immunodeficiency virus infection as IgA, anti-p24 antibodies, p24 antigenemia, CD4+ lymphocytes, beta 2-microglobulin, and the clinical status. The prognostic relevance of plasma von Willebrand factor and tissue-type plasminogen activator levels at the time of entry into the study was then investigated in a cohort of 65 of the 85 patients who had follow-up during a median period of 22 months. The median survival time for all patients was 39 months after the first consultation. A plasma von Willebrand factor level greater than 200% of the control value had a positive predictive value of 86% for determining nonsurvivors; the median survival time for such patients was 9 months after the first consultation. A positive predictive value of 100% in recognizing nonsurvivors was found for tissue-type plasminogen factor plasma levels greater than 20 ng/ml; the median survival time for these patients was 2 months after the first consultation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Potentiation of plasminogen activation by an anti-urokinase monoclonal antibody due to ternary complex formation. A mechanistic model for receptor-mediated plasminogen activation.

We have observed that a murine IgG1 monoclonal antibody directed against human urokinase-type plasminogen activator (uPA) greatly potentiates pro-uPA-mediated plasminogen activation. This effect was dependent on the interaction between the immunoglobulin and the kringle domain of pro-uPA and could be competed efficiently by kringle-containing proteolytic fragments of uPA. In addition, the potentiation could also be competed by the lysine analog 6-aminohexanoic acid, an antagonist of plasminogen binding. This unexpected plasminogen binding dependence was found to be due to a carboxyl-terminal lysine residue on the immunoglobulin gamma chain, which by analogy with other proteins represents a potential binding site for plasminogen. Removal of this residue with carboxypeptidase B resulted in a complete abolition of the potentiation. It appears therefore that the potentiatory effect involves a novel mechanism with the antibody acting to provide a specific template for the assembly of a ternary complex involving pro-uPA/uPA and plasminogen, enabling them to interact in a catalytically favorable manner. This interpretation was confirmed by studying the kinetics of plasminogen activation by the complex between active, two-chain uPA and the antibody, which resulted in an overall 50-fold increase in reaction efficiency (kcat/Km), primarily due to a reduction in Km from 20 to 0.1 microM. Pro-uPA activation by plasmin was also accelerated, although to a lesser extent. The potentiation due to complex formation also provides a mechanism for the initiation of this system, dependent only on the low intrinsic proteolytic activity of the zymogen forms. The effects observed here, mediated by ternary complex formation, simulate the effects we have previously observed on assembly of the uPA receptor-mediated cellular plasminogen activation system and may therefore represent a mechanistic model for both its activity and initiation.

Amino Acid Sequence↗
PubMed1992

Expression of plasminogen activator and plasminogen activator inhibitor mRNA in human fibroblasts grown on different substrates.

mRNA levels for urokinase type plasminogen activator (uPA), tissue type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) were examined in human diploid (neonatal foreskin) fibroblasts grown in 200-ml microcarrier suspension culture. Four different substrates were used. These included gelatin-coated polystyrene plastic, DEAE-dextran, glass-coated polystyrene plastic and uncoated polystyrene plastic. Our previous studies have shown that culture fluids from diploid fibroblasts grown on DEAE-dextran contained higher levels of plasminogen-dependent fibrinolytic activity than culture fluids from the same cells grown on other substrates. The increased plasminogen activator activity was due largely to elevated amounts of tPA (In Vitro Cell. Develop. Biol. 22: 575-582, 1986). The present study shows that there is a corresponding elevation of tPA mRNA in diploid fibroblasts cultured on DEAE-dextran relative to the other substrates. There does not appear to be any difference in uPA mRNA or in mRNA for PAI-1 or PAI-2 produced by the same cells on the four substrates. These data suggest that the influence of the substrate on plasminogen activator production is mediated at the genetic level.

Cell Division↗
PubMed1997

Expression of plasminogen activators and plasminogen activator inhibitor 1 in dedifferentiated chondrosarcoma.

BACKGROUND: The plasminogen activator system plays an important role in different malignant tumors. These enzymes participate in the destruction of intercellular matrices and basement membranes and/or can modulate the growth potency of tumor cells and may even promote metastases. In this study, the expression of three glycoproteins that play a role in the plasminogen activator system as activators of proteolysis-urokinase type plasminogen activator (u-PA), tissue type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were studied in various components of dedifferentiated chondrosarcomas of bone. METHODS: The expression of u-PA, t-PA, and PAI-1 was investigated in 10 dedifferentiated chondrosarcomas and 14 conventional chondrosarcomas. The plasminogen activator/inhibitor glycoproteins were visualized immunohistochemically on paraffin sections and the levels of expression were assessed semiquantitatively. RESULTS: In dedifferentiated chondrosarcoma, high grade dedifferentiated components displayed strong, diffuse coexpression of u-PA, t-PA, and PAI-1. For all glycoproteins studied, the immunoreactivity was significantly increased compared with the reactions in the low grade cartilaginous component of the same tumor and conventional chondrosarcoma. In the latter, u-PA, t-PA, and PAI-1 expression was found to be enhanced at invasive foci and in regions of endochondral ossification. CONCLUSIONS: The current study documents the overexpression of u-PA, t-PA, and PAI-1 in dedifferentiated chondrosarcoma and suggests involvement of the plasminogen activator system in the biology of these tumors.

Bone Neoplasms↗
PubMed1983

Plasminogen Paris I: congenital abnormal plasminogen and its incidence in thrombosis.

An abnormal plasminogen was discovered because of a decreased level of plasminogen activity in plasma contrasting with a normal level of plasminogen antigen concentration. The same discrepancy was found in the purified plasminogen. The molecular abnormality seems to be inherited. The patient is a heterozygote. The experimental findings can be explained by assuming that half of the plasminogen is normal, while the other half is an inactive mutant protein, without catalytic activity after SK or UK addition. There was no binding of labeled DFP and a decreased binding of TLCK to the abnormal plasminogen. The role of the abnormal plasminogen in thrombotic tendency is uncertain since the patient is the only one who has suffered a thrombotic accident, while her relatives who present the same defective plasminogen have not had thrombotic problems.

Blood Coagulation↗
PubMed1997

Glycated proteins modulate tissue-plasminogen activator-catalyzed plasminogen activation.

Plasminogen activation by tissue-plasminogen activator (t-PA) is accelerated by the presence of a macromolecular surface, which acts as a template that brings enzyme and substrate in close proximity. Modification of lysine residues, which are important for this template function, occurs in diabetic patients as a consequence of glycation of proteins. In this study, we investigated the effects of glycation of fibrin and other proteins in t-PA-catalyzed plasmin formation. Plasminogen activation on glycated fibrin(ogen) was increased compared to non-glycated fibrin(ogen), which could fully be attributed to an increased affinity of t-PA for glycated fibrin(ogen). Binding of plasminogen to glycated fibrin was increased, but did not contribute to increased plasminogen activation. Both plasminogen activator inhibitor-1 (PAI-1) binding and activity were increased on glycated fibrin. Induction of template function in plasminogen activation was also observed on immobilized glycated bovine serum albumin (BSA) and human gamma-globulins (IgG). Increased plasmin generation at sites of deposition of glycated proteins may lead to increased extracellular matrix breakdown and thereby affect the integrity of the endothelial monolayer. Moreover, soluble glycated BSA and glycated IgG can inhibit t-PA binding to immobilized glycated fibrin and interfere with fibrinolysis in diabetic patients.

Binding, Competitive↗