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:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activators (PAs) convert plasminogen to plasmin by the cleavage of the Arg-Val bond. There are two distinct types of PA, tissue type (t-PA) released from the endothelial cells of the blood vessels and urinary type (u-PA) released from urinary tubules. u-PA was found to be released from activated macrophages and virally transformed cells. t-PA was also found to be released from breast cancer cells induced by carcinogens or melanoma cells. In structure, t-PA has a finger domain homologous to fibrin-binding domain of fibronectin and a growth factor domain homologous to the epidermal growth factor. u-PA has no finger domain but has a growth factor domain. It is proposed that PA may be important in tumor growth due to the stimulation of tumor cells through binding of growth factor domain to its receptor of tumor cells. Another hypothesis is that PA may activate procollagenase to collagenase, which digests collagen to facilitate tumor growth. We have measured the concentrations of t-PA and u-PA in plasma, urine and tumor tissues of patients with cancer of the digestive tract and patients with uterine or ovarian tumors. The results indicate that the concentrations of u-PA increased in urine, plasma and cancer tissues of patients with cancer of the digestive tracts whereas no increase was observed in t-PA levels. On the other hand, the concentration of t-PA increased mostly in plasma of patients with uterine and ovarian cancers, but t-PA levels in tissues did not increase in patients with uterine and ovarian cancer.
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PMID:Plasminogen activators: possible roles in cell proliferation. 250 84

Mucoid effusions from 39 children with secretory otitis media, altogether 42 specimens, were analyzed for proteolytic activity using radial caseinolysis procedures, for fibronectin using a solid-phase enzyme immunoassay, and for fibronectin fragmentation using immunoblotting. All samples contained proteolytic activity, tentatively identified as plasmin on the basis of comigration with purified human plasmin in zymographic analysis. In 19 specimens the plasmin level exceeded 1 microgram/mg of protein; the highest value recorded was 18.7 micrograms/mg. Low levels of net plasminogen activator activity were found in 12 specimens and identified as urokinase according to comigration with the urokinase standard in zymography. Fibronectin was detected in all but one of the 42 specimens; in seven specimens the levels exceeded those in normal plasma, calculated per milligram of total protein. Extensive fragmentation of fibronectin was found in 19 specimens, correlating with high plasmin levels. The results are indicative of an ongoing proteolytic process in secretory otitis media and suggest that plasmin-caused degradation of the fibronectin-containing basement membrane and subsequent formation of granulation tissue may be involved in the development of adhesive middle ears.
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PMID:Plasmin and fibronectin degradation in chronic secretory otitis media. 252 Dec

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.
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PMID:Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S. 252 Dec 76

The effects of fibronectin and fragments of its limited proteolysis by plasmin on the proliferative activity of human embryo fibroblasts in culture were studied. It was found that native fibronectin and its fragments with Mr greater than or equal to 120 kD do not exert either a stimulating or inhibiting influence, whereas the 15-43 kD fragments significantly stimulate cell proliferation. The stimulating effect increases with a rise in the fragment concentration, reaching a maximum at 12-25 micrograms/ml and decreases at their higher concentrations. The preparation of proliferation-stimulating fragments contains no proteinases admixtures that are active at neutral pH and does not possess any intrinsic proteolytic activity. The proliferation-stimulating activity does not change after removal of collagen-binding fragments.
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PMID:[The effect of fibronectin fragments on proliferative activity of fibroblasts]. 252 18

The plasma concentration of human lipoprotein(a) [Lp(a)] is correlated with the risk of heart disease. A distinct feature of the Lp(a) particle is the apolipoprotein (a) [apo(a)], which is associated with apoB-100, the main protein component of low-density lipoprotein. We now report that apo(a), which has extensive homology to plasminogen, binds to immobilized fibronectin. The binding of Lp(a) was localized to the C-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) with fibronectin resulted in fragmentation of fibronectin. The cleavage pattern, as visualized by gel electrophoresis and immunoblotting, was reproducibly obtained with Lp(a) purified from five different individuals and was distinct from that obtained upon proteolysis of fibronectin by plasmin or kallikrein. The use of synthetic peptide substrates demonstrated that the amino acid specificity for Lp(a) was arginine rather than lysine. The proteolytic activity of Lp(a) was localized to apo(a) and experiments with inhibitors indicated that the proteolytic activity was of serine proteinase-type.
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PMID:Lipoprotein(a) binds to fibronectin and has serine proteinase activity capable of cleaving it. 253 57

Plasmin can degrade fibronectin and laminin, two important components of the extracellular matrix facilitating cell sliding and healing following a wound. In this study we investigated the relationship between the tear fluid level of plasmin and plasminogen activator and the healing of a corneal wound. Anterior keratectomy (AKE) was performed for seven rabbits (11 eyes). Eight eyes were rewounded after re-epithelialization. Tear fluid samples were collected with capillaries before wounding and during wound healing. Plasmin and plasminogen activator (PA) activities were determined using radial caseinolysis procedures. After AKE the plasmin concentrations increased rapidly, from a mean (+/- SEM) of 3.9 +/- 0.9 micrograms/ml to a mean of 37.9 +/- 7.8 micrograms/ml (p less than 0.01), and decreased during wound healing. Rewounding also resulted in an increase in plasmin concentration in the tear fluid (from a mean of 2.9 +/- 0.6 micrograms/ml to a mean of 5.0 +/- 1.1 micrograms/ml; p greater than 0.05). The PA activity showed an inverse trend as it decreased after AKE from a mean of 2.0 +/- 0.6 IU/ml to a mean of 0.3 +/- 0.1 IU/ml (p less than 0.001). During wound healing and re-epithelialization, the PA activity increased again, to 2.1 +/- 0.3 IU/ml (p less than 0.001). Abrasion of the newly grown epithelium in eight eyes caused a second elevation of PA activity which was not significant. This study demonstrates a close association between the healing of corneal wounds and changes in the plasmin and PA activities in tear fluid. Determination of the activity of these enzymes may therefore be useful for monitoring corneal wound healing.
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PMID:Plasmin and plasminogen activator activities in tear fluid during corneal wound healing after anterior keratectomy. 253 68

Plasmin, immobilized on Sepharose, was used for isolation of human blood plasma fibronectin fragments obtained after proteolysis. Under definite conditions the major part of the fibronectin fragments, liberated during proteolysis, remained to be bound to plasmin-Sepharose. As shown by electrophoretic analysis, the fraction of fragments bound to plasmin-Sepharose constituted mainly "heavy" (greater than or equal to 120 kD) peptides and one "light" (29 kD) peptide, while only "light" fragments (less than or equal to 45 kD) were detected in the free unbound fraction. These unbound to plasmin-Sepharose fibronectin fragments were found to stimulate proliferation of human embryonal fibroblasts in cell culture, whereas the plasmin-Sepharose bound peptides did not exhibit any effects on proliferation.
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PMID:[Isolation of fibronectin peptide fragments of various sizes and biological activity using affinity chromatography on an immobilized plasmin]. 253 45

Basement membranes are thin layers of matrix separating parenchymal cells from connective tissue. Their ultrastructure consists of a three-dimensional network of irregular, fuzzy strands referred to as "cords"; the cord thickness averages 3-4 nm. Immunostaining reveals that the cords are composed of at least five substances: collagen IV, laminin, heparan sulfate proteoglycan, entactin, and fibronectin. Collagen IV has been identified as a filament of variable thickness persisting after the other components have been removed by plasmin digestion or salt extraction. Heparan sulfate proteoglycan appears as sets of two parallel lines, referred to as "double tracks," which run at the surface of the cords. Laminin is detected in the cords as diffuse material within which thin wavy lines may be distinguished. The entactin and fibronectin present within the cords have not been identified as visible structures. The ability of laminin, heparan sulfate proteoglycan, fibronectin, and entactin to bind to collagen IV has been demonstrated by visualization with rotary shadowing and/or biochemical studies. Incubation of three of these substances-collagen IV, laminin (with small entactin contamination), and proteoglycan-at 35 degrees C for 1 hr resulted in a precipitate that was sectioned for electron microscopic examination and processed for gold immunolabeling for each of the three incubated substances. Three structures are present in the precipitate: 1) a lacework, exclusively composed of heparan sulfate proteoglycan in the form of two parallel lines, similar to double tracks; 2) semi-solid, irregular accumulations, composed of the three initial substances distributed on a cord network; and 3) convoluted sheets, which are also composed of the three initial substances distributed on a cord network but which, in addition, have the uniform appearance and thickness of the lamina densa of basement membrane. Hence these sheets are closely similar to the main component of authentic basement membranes.
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PMID:Structure, composition, and assembly of basement membrane. 267 90

In vitro experiments have shown that proteases such as trypsin, kallikrein and plasmin may split plasma fibronectin, yielding changes in apparent mass concentration, i.e.: a decrease when using immunonephelometry (IN), and an increase when using electroimmunoassay (EIA). In the present in vivo study, plasma from 49 patients with severe infections was assayed for fibronectin by IN and EIA, and for prekallikrein, plasminogen and antithrombin. In patients with normal prekallikrein (n = 26) and plasminogen (n = 23), the agreement between the two fibronectin assay methods was good (ratio EIA/IN = 0.99 +/- 0.06); a similar good agreement was found in 45 healthy blood donors (ratio 0.97 +/- 0.02). In contrast, the 20 patients with low prekallikrein showed fibronectin values that were significantly higher by EIA than by nephelometry (ratio 1.27 +/- 0.10, p less than 0.01). Similarly, the 26 patients with low plasminogen had a significantly increased ratio (1.21 +/- 0.09, p less than 0.05). No such difference was seen, however, between patients with low or normal antithrombin. Thus, kallikrein and plasmin activation in vivo appear to increase the fibronectin concentration measured by EIA, possibly due to the formation of small fragments with increased electrophoretic motility.
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PMID:Influence of plasma protease activation on electroimmunoassay and nephelometry of plasma fibronectin in sepsis. 269 1

Low density lipoproteins (LDL) were modified after incubation with fibrinogen and fibronectin at physiological concentrations in presence of thrombin and, following the fibrin formation, in presence of plasmin. The modified LDL (LDL-F) isolated from plasmin digested fibrin by means of gel permeation chromatography on Sepharose 6B, were associated with fibrinogen and fibronectin degradation products. The LDL-F differed from control LDL in their physico-chemical properties: LDL-F contained the degraded apoprotein B, its electrophoretic mobility was increased, cholesterol/protein ratio as well as flotation coefficient at d = 1.063 were decreased. The effect of LDL-F on lipid accumulation was studied. Content of cholesterol esters in macrophages incubated with LDL-F was higher 3.8-fold as compared with that of the cells incubated with control LDL. Thus, after incubation of LDL with fibrinogen and thrombin, 20% of the lipoprotein was bound to fibrin. The data obtained suggest that thrombosis may promote both LDL deposition in the vascular intercellular matrix and cellular lipid accumulation.
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PMID:[Atherogenic modifications of low density lipoproteins during fibrin formation and fibrinolysis]. 274 16


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