Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Comparison of the primary structures of high-Mr urokinase and tissue-type plasminogen activator reveals a high degree of structural homology between the two proteins, except that tissue activator contains a 43 residue long amino-terminal region, which has no counterpart in urokinase. We show that this segment is homologous with the finger-domains responsible for the fibrin-affinity of fibronectin. Limited proteolysis of the amino-terminal region of plasminogen activator was found to lead to a loss of the fibrin-affinity of the enzyme. It is suggested that the finger-domains of fibronectin and tissue-types plasminogen activator have similar functions and that the finger-domains of the two proteins evolved from a common ancestral fibrin-binding domain.
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PMID:Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator. 668 59

We investigated in vitro chemotactic responses to fibronectin and laminin, invasion through reconstituted basement membrane (Matrigel) and secretion of matrix metalloproteinases and plasminogen activators by non-tumorigenic Mel-ab melanocytes; B16 melanoma; and the metastatic sublines, B16F1, B16F10 and B16BL6. In vitro chemotactic and invasive ability were not associated with in vivo metastatic potential. Secretion of various matrix-degrading enzymes was not related to in vitro invasion. Conditioned media from all B16 melanoma sublines, but not from Mel-ab cells, contained the M(r) 92,000 progelatinase. The activated M(r) 85,000 species was present only in conditioned media from Mel-ab, B16 and B16F1 cells. Mel-ab cells secreted copious amounts of the M(r) 72,000 progelatinase, and the M(r) 66,000 active form was also present in conditioned media. Secretion of the M(r) 72,000 progelatinase by B16 melanoma sublines was markedly lower, and only conditioned media from B16 cells contained the activated M(r) 66,000 form. Furthermore, cell lysates of Mel-ab cells contained a M(r) 67,000 metalloproteinase which was absent in the tumor cells. All cells secreted tissue plasminogen activator; however, the metastatic B16F1, B16F10 and B16-BL6 cells also secreted urokinase plasminogen activator. Our results indicate that matrix metalloproteinase secretion by itself is not associated with tumorigenicity or metastatic potential. Secretion of urokinase plasminogen activator, and not tissue plasminogen activator, reflected the metastatic characteristics of the B16 melanoma tumor sublines.
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PMID:Differences in expression of metalloproteinases and plasminogen activators in murine melanocytes and B16 melanoma variants: lack of association with in vitro invasion. 755 59

High ambient glucose concentration, linked to vascular complications in diabetes in vivo, modulates mRNA expression of fibronectin, collagen, tissue-type plasminogen activator, and plasminogen activator inhibitor and induces delayed replication and excess cell death in cultured vascular endothelial cells. To determine the role of high ambient glucose (30 mmol/l) in apoptosis, paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were exposed to both high (30 mmol/l) and low (5 mmol/l) concentrations of glucose for short-term (24, 48, and 72 h) and long-term (13 +/- 1 days) experiments. Incubation of HUVECs with high glucose for > 48 h increased DNA fragmentation (13.7 +/- 6.5% of total DNA, mean +/- SD) versus cultures kept in 5 mmol/l glucose (10.9 +/- 5.6%, P < 0.005), as measured by [3H]thymidine assays. Data were confirmed by apoptosis-specific fluorescence-activated cell sorter analysis of confluent HUVEC cultures, which displayed after long-term exposure to 30 mmol/l glucose a 1.5-fold higher prevalence of apoptosis than control cultures exposed to 5 mmol/l glucose (P < 0.005). In contrast, no increase in DNA fragmentation in response to 30 mmol/l glucose was seen for standardized cell lines (K 562, P 815, YT) and fibroblasts. Expression of clusterin mRNA, originally reported to be a molecular marker of apoptosis, was only slightly affected by short-term (24-h) high-glucose exposure but was significantly reduced after long-term incubation in 30 mmol/l glucose (82.2 +/- 13.8% of control) versus 5 mmol/l glucose, which questions the role of clusterin gene expression as a marker of apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-glucose--triggered apoptosis in cultured endothelial cells. 758 31

It was the aim of this study to investigate possible effects of biomaterials used to produce vascular grafts on the fibrinolytic system of endothelial cells. Therefore growth conditions for human umbilical vein endothelial cells on polytetrafluoroethylene and on polyurethane were optimized. Tissue culture polystyrene was used as a control material. We could demonstrate that precoating of the materials with fibronectin significantly increased the growth rate of human umbilical vein endothelial cells on these materials. Furthermore, we showed that human umbilical vein endothelial cells grown on polytetrafluoroethylene or polyurethane released more plasminogen activator inhibitor-1 and tissue type-plasminogen activator into the conditioned media than did human umbilical vein endothelial cells grown on tissue culture polystyrene. Human umbilical vein endothelial cells cultured on polytetrafluoroethylene also deposited more plasminogen activator inhibitor-1 into the extracellular matrix than did control cells grown on tissue culture polystyrene. Our results give evidence that human umbilical vein endothelial cells grown on two biomaterials used to construct vascular grafts, namely polytetrafluoroethylene and polyurethane, produce tissue-type plasminogen activator as well as plasminogen activator inhibitor-1, two major components of the fibrinolytic system also expressed by endothelial cells in vivo. In conclusion, our data suggest that endothelial cells grown on vascular grafts show functional integrity concerning their fibrinolytic system, which in turn might contribute to reduce the thrombogenic properties of the graft material.
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PMID:Growth and fibrinolytic parameters of human umbilical vein endothelial cells seeded onto cardiovascular grafts. 777 69

This prospective, nested, case-control study investigated whether elevated plasma cellular fibronectin concentrations previously reported in preeclamptic women likely reflect endothelial dysfunction. In addition to higher maternal plasma concentrations of cellular fibronectin, we found higher levels of von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1 in maternal plasma, providing biochemical corroboration of endothelial dysfunction in severe preeclampsia.
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PMID:Biochemical corroboration of endothelial involvement in severe preeclampsia. 784 35

Curli are fimbrial structures expressed by Escherichia coli that specifically interact with matrix proteins such as fibronectin and laminin. Similar structures are also expressed by Salmonella enteritidis and have been denoted thin aggregative fimbriae. Bacteria expressing curli and thin aggregative fimbriae were found to bind radiolabelled plasminogen as well as the tissue-type plasminogen activator (t-PA). By contrast, E. coli carrying a gene locus with an insertionally inactivated chromosomal curlin subunit were unable to bind the two human proteins. The purified subunit polypeptides of curli and thin aggregative fimbriae bound plasminogen and t-PA with high affinity (1 x 10(8) to 2 x 10(8) M-1). The binding of plasminogen and t-PA to curli-expressing E. coli was only partially inhibited by fibronectin and laminin. Plasminogen absorbed from human plasma by curli-expressing E. coli was readily converted to plasmin by t-PA; both plasmin and t-PA were functionally active when bound to the bacteria. A simultaneous binding of fibrinolytic proteins and matrix proteins to fimbriae of E. coli and S. enteritidis could provide these pathogens with both adhesive and invasive properties.
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PMID:Plasminogen, absorbed by Escherichia coli expressing curli or by Salmonella enteritidis expressing thin aggregative fimbriae, can be activated by simultaneously captured tissue-type plasminogen activator (t-PA). 788 28

We performed hemostatic studies on eight patients undergoing clipping of unruptured cerebral aneurysms to assess the influence of intracranial surgery itself on hemostasis. Blood samples were collected from each patient 10 times: before and after the induction of anesthesia and 6, 12, and 24 hours and 2, 3, 5, and 7 days immediately after surgery. The changes and our interpretation of them include the following: 1) the elevation of thrombin antithrombin III complex levels (activation of blood coagulation) was transient and monophasic; 2) the elevation of plasmin alpha 2-antiplasmin complex and D-dimer levels (activation of fibrinolysis) was biphasic, despite the monophasic elevation of tissue plasminogen activator or plasminogen activator inhibitor-1 levels; 3) the elevation of beta-thromboglobulin and platelet-factor-4 levels (activation of platelet) was also biphasic; 4) fibrinogen level and alpha 2-antiplasmin activity increased in the acute phase of the postoperative course (acute phase reaction); 5) the changes in hematocrit appeared to parallel those in various other parameters, especially platelet count, antithrombin III, and plasminogen levels for 1 or 2 days after surgery; 6) fibronectin appeared to be consumed in the acute phase of postoperative course; and 7) general anesthesia did not significantly affect hemostasis. These serial changes seem to be related to the activation of hemostatic systems after intracranial surgery and the subsequent acute phase reaction.
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PMID:Serial changes in hemostasis after intracranial surgery. 793 48

To assess the effect of interleukin-6 (IL-6) on the coagulation and the fibrinolytic systems, we administered a single subcutaneous injection of recombinant glycosylated human interleukin-6 (r-hIL-6) 100 micrograms per kg body weight) to four baboons (Papio ursinus). Four saline injected baboons served as controls. In serial plasma or serum samples collected over a period of seven days we measured several key parameters of the coagulation and the fibrinolytic systems, IL-6 and a set of acute phase proteins. Three hours after the injection, the serum IL-6 levels peaked at 50 ng/ml and then gradually declined with a terminal half-life of around 4 hours. The biological efficacy was demonstrated by the significant increases of several acute phase proteins, circulating platelets and the decrease of prealbumin and fibronectin. Between days 1 and 3, marked effects on the coagulation system were observed with a prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time. Plasma concentrations of fibrinopeptide A and D-dimer increased. The antithrombin III antigen and activity levels decreased, but the thrombin-antithrombin III complex concentrations did not change. The fibrinolytic system rapidly showed striking modifications after 6-8 hours, the concentrations of tissue-type plasminogen activator and of plasminogen activator inhibitor type 1 peaked at respectively four and thirty times the basal concentrations. No changes were seen in the control group. We conclude that besides its well-known acute phase inducing and hematopoietic activities, subcutaneous rhIL-6 also modulates several parameters of the coagulation and the fibrinolytic systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons. 794 65

The aim of this study was to compare the secretory response of the vascular wall in vivo to DDAVP (i.v. 0.3 microgram/kg, 30 min) and to venous occlusion (VO, 20 min) in control healthy subjects, patients with von Willebrand's disease type I (vWd I) and patients with von Willebrand's disease type III (vWd III). In controls (n = 10) and vWd I (n = 12), DDAVP induced a 2 to 3-fold rise in plasma von Willebrand factor antigen (vWf: Ag), factor VIII coagulant activity (VIII: C) and tissue--type plasminogen activator antigen (t-PA:Ag). VO was less effective in increasing vWf: Ag and VIII:C but produced a greater rise in t-PA:Ag. Large increments (over 10-fold) were observed in plasmin-alpha 2-antiplasmin complexes following both stimuli. In vWd III (n = 10), DDAVP and VO failed to increase vWf:Ag, VIII:C and t-PA:Ag. No significant changes in plasmin-alpha 2-antiplasmin complexes were observed in this group. Moreover, the baseline t-PA:Ag values were significantly lower in vWd III (2.17 +/- 1.13 ng/ml) than in controls (4.84 +/- 1.97 ng/ml, p < 0.001). A significant increase in urokinase--type plasminogen activator antigen (u-PA:Ag) was found only in controls after VO. Neither controls nor patients with vWd showed any changes in plasma fibronectin levels following DDAVP. The low t-PA:Ag results and the abnormal fibrinolytic response to DDAVP and VO in patients with severe (type III) vWd indicate that their endothelial cell abnormality is more extensive than the defect in the synthesis or release of vWf.
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PMID:Secretory response of the vessel wall to DDAVP and venous occlusion in von Willebrand's disease. 799 99

In recent years, it is known that endothelial cells play an important role in the genesis of some diseases, but there are only few papers dealing with the role of endothelial cells in leukemia. In this study some of the active factors released by the endothelial cells in patients with acute leukemia such as von Willebrand factor, prostaglandin, fibronectin, tissue-type plasminogen activator and its inhibitor were determined. It was found that the levels of these factors changed significantly in patients with acute leukemia, as compared with those in normal controls, especially in cases with bleeding tendency and infection. The possible mechanism and the clinical significance were discussed.
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PMID:[Active factors released by endothelial cells in acute leukemia]. 804 83


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