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)

Fibronectin was isolated from porcine plasma by affinity chromatography with gelatin-linked Sepharose 4B. Porcine fibronectin had a chemical composition similar to those of human and other fibronectins and reacted with antiserum raised against human fibronectin. It showed hemagglutination activity with trypsin-treated rabbit erythrocytes, though the activity was far less than that of human fibronectin. Porcine plasma fibronectin consisted of two subunit chains of about 230,000-daltons linked by disulfide bonds(s). Limited proteolysis of this protein with porcine liver cathepsin B yielded five major fragments which were investigated by affinity chromatography with gelatin- and heparin-linked Sepharose 4B. One fragment (Mr = 50,000) was bound to gelatin but not to heparin, while the remaining four were bound to heparin but not to gelatin, suggesting that plasma fibronectin takes a discrete domain structure with respect to interaction with these two macromolecules. The three larger heparin-binding fragments, Mr = 175,000, 150,000, and 130,000 were eluted with different concentrations of a mixture of NaCl and urea from the heparin-column, suggesting that they have different interactions with heparin, the 130,000-dalton fragment being the one with the strongest interaction. After reduction with 2-mercaptoethanol, the 175,000-dalton fragment was converted to the 150,000-dalton region fragment, which, together with the unchanged 150,000-dalton fragment, appeared to be equivalent in amount to the 130,000-dalton fragment. This finding suggests that the 150,000- and 130,000-dalton fragments may have originated from different subunit chains. Since the 175,000-dalton fragment was not produced by cathepsin B digestion of fibronectin which had been treated with plasmin, it was concluded that the 175,000-dalton fragment contained interchain disulfide bond(s) which had linked the native subunit chains. These results suggest that porcine plasma fibronectin has non-identical subunit chains composed of domains which differ in interaction with heparin and in susceptibility to cathepsin B.
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PMID:Characterization of porcine plasma fibronectin and its fragmentation by porcine liver cathepsin B. 645 32

Amyloid beta protein (beta/A4) is deposited in senile plaques of patients with Alzheimer's disease. This protein is derived from a larger membrane-associated protein, termed amyloid precursor protein (APP). The constitutive processing of APP occurs at the central portion of beta/A4, resulting in the release of large N-terminal peptides. We have purified these peptides from the culture medium of cDNA-transfected COS-1 cells. Some of the isoforms contain the Kunitz-type protease inhibitor (KPI) domain and strongly inhibit trypsin, chymotrypsin and plasmin, but do not inhibit kallikrein, prolyl endopeptidase or granzyme A. The peptides also do not inhibit cysteine proteases such as cathepsin B or calpain. Soluble APPs lacking the KPI domain fail to inhibit any of these proteases. The results indicate that the KPI domain in soluble APPs has protease inhibitory activity against certain serine proteases.
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PMID:Inhibitory spectra of purified protease nexin-II and related proteins towards cellular proteinases. 790 50

Urokinase-type plasminogen activator (uPA), uPA receptors, and cathepsin B were quantitated by using an immunological method, enzyme-linked immunosorbent assay, and amidolytic activity assays in 15 malignant and 10 benign epithelial ovarian tumors. The levels of uPA and uPA receptors, as well as cathepsin B, were found to be higher in membrane preparations obtained from malignant tumors than in those obtained from benign tumors. Acid-treated membranes acquired the ability to bind uPA, indicating that uPA is bound to a specific surface receptor that is not completely saturated. Levels of single-chain uPA (pro-uPA) and high-molecular-weight uPA in membrane preparations were measured by immunoadsorbent-amidolytic assay. The finding of a significant increase in amidolytic activity following activation of uPAs by plasmin suggested that less than half (30-40%) of all membrane immunoreactive uPAs is present in the enzymatically inactive pro-uPA form. In the membranes of malignant tumors, levels of uPA receptor and cathepsin B did not vary with stage of disease. On the other hand, we found that the level of receptor-bound uPA antigen/activity was significantly increased in advanced malignant tumors. Receptor-bound uPA may play an important role in determining invasive potential of tumor cells. Since ovarian cancer cells produce both pro-uPA and cathepsin B, the possibility of activation of tumor cell-derived pro-uPA by cellular protease cathepsin B must be considered.
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PMID:Increased cell-surface urokinase in advanced ovarian cancer. 834 Feb 51

In vitro activation of pro-cathepsin B purified from ascitic fluid of ovarian carcinomas by serine proteinases was studied. Both elastase and cathepsin G from human leucocytes were found to be activators, on the basis of generation of cathepsin B activity and processing of the precursor. These results represent a new cooperative pathway between cancer cells and host cells. The urokinase-type plasminogen activator activated pro-cathepsin B faster than leucocyte proteinases. A new relationship is emerging between the cysteine proteinases and the plasmin-activation system. Both pathways suggest an important role of cathepsin B in the proteolytic cascade associated with tumour invasion.
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PMID:In vitro activation of pro-cathepsin B by three serine proteinases: leucocyte elastase, cathepsin G, and the urokinase-type plasminogen activator. 840 67

In orthotopic liver transplantation (OLT) hyperfibrinolysis seems to be of causative importance for intra- and postoperative bleeding. Although recently hyperfibrinolysis has been successfully reduced by intraoperative aprotinin treatment, small increases of fibrinolysis still remain during OLT. Originally, tissue-type plasminogen activator (t-PA) was considered to be responsible for the increases, but the efficacy of aprotinin which inhibits besides plasmin also kallikrein and urokinase-type plasminogen activator (u-PA) suggested also a role for the intrinsic and contact system-dependent plasminogen activators. We investigated the role of u-PA. From 29 patients undergoing OLT with intraoperative aprotinin infusion arterial blood samples were taken at 7 different time points. The preoperative median values for u-PA antigen (u-PA Ag) and plasmin-activatable single-chain u-PA (scu-PA) levels, which were more than 2-fold above normal (both: p < 0.01), decreased slightly during the preanhepatic phase and remained unchanged during the anhepatic phase. With reperfusion of the graft liver the two levels decreased significantly (p = 0.0003 and p = 0.006, respectively) to almost normal values, probably due to clearance by the graft liver. Active two-chain u-PA (tcu-PA) was preoperatively 2-fold above the detection limit, remained stable during the preanhepatic phase and increased 2-fold in the anhepatic phase (p = 0.0018). As expected tcu-PA also relapsed upon reperfusion, but to the preoperatively enhanced level, possibly caused by sustained activation of scu-PA by cathepsin B. t-PA activity levels were at the upper end of the normal range preoperatively, slightly increased during preanhepatic and anhepatic phases and decreased significantly with reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evolution of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) in orthotopic liver transplantation (OLT). 844 39

Fifteen tripeptide analogues of leupeptin containing either a C-terminal argininal or lysinal were synthesized. The synthetic analogues were tested, using spectrophotometric assay techniques, as inhibitors of trypsin, kallikrein, thrombin, plasmin, and cathepsin B. The lysinal analogues were fairly selective as inhibitors of cathepsin B activity. Acetyl-L-leucyl-L-valyl-L-lysinal (21) showed a stronger inhibition of cathepsin B (IC50 = 4 nanomolar) than leupeptin. Acetyl-L-phenylalanyl-L-valyl-L-argininal (2i) was found to be a good inhibitor of cathepsin B (IC50 = 0.039 microM), thrombin (IC50 = 1.8 microM), and plasmin (IC50 = 2.2 microM).
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PMID:Inhibition studies of some serine and thiol proteinases by new leupeptin analogues. 847 5

The tripeptide compounds, Glu-Arg-Pro-amide (ERPm), D-Pro-Thr-Trp-amide (dPTWm) and thioproline-Thr-Trp (tPTW), were obtained by screening of synthetic peptides for growth-inhibitory activity toward cultured transformed cells. The effects of these peptide compounds on proteases were investigated and the results showed that these compounds enhanced the amidolytic activity of serine proteases despite the fact that each reaction was carried out under optimal conditions. ERPm stimulated the activities of trypsin, chymotrypsin, thrombin, plasmin urokinase and elastase. dPTWm also showed similar effects except that toward chymotrypsin. tPTW elevated the activity only of trypsin, chymotrypsin and thrombin. Stimulation of trypsin activity by these compounds was also confirmed by using casein as a substrate. None of these compounds affected the amidolytic activities of metalloproteinases (MMP-1 and MMP-9), cysteine proteinases (m- and mu-calpains, cathepsin B and papain) or an exopeptidase (leucine aminopeptidase). The activation was at least partly due to the stabilization of the catalytic activity of proteases as well as prevention of autolysis.
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PMID:Enhancement of catalytic activities of serine proteases by tripeptides compounds. 863 1

A 3-fold increase in active renin was found after a kidney cortex extract was incubated with plasma from either normal or nephrectomized rats (0.34 +/- 0.04 to 1.34 +/- 0.08 and 1.60 +/- 0.06 micrograms Angiotensin I/mg tissue/hr, respectively). A plasma protein that activates renal renin was purified 900-fold. Purification of the protein was achieved by a combination of ammonium sulfate fractionation, molecular filtration on Sephacryl S-200 HR and ion-exchange chromatography on Mono Q HR 5/5 associated to an fast performance liquid chromatography (FPLC) system. The protein shows a molecular weight of approximately 54,000 Da. Renin activation was not inhibited by serine protease inhibitors, such as phenylmethyl sulfonylfluoride, aprotinin, soybean trypsin inhibitor and N-tosyl-L-phenylalanine chloromethyl ketone or by the cystein protease inhibitors N-ethylmaleimide and leupeptin. By using enzyme inhibitors, it was found that the activation process is not mediated by kallikrein, plasmin, tonin, cathepsin B or trypsin-like enzymes. From these results, we conclude that there is in circulating plasma a previously unidentified enzyme capable of activating inactive kidney renin. However, the possibility that this protein acts by activating the renin-substrate reaction cannot be dismissed.
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PMID:Activation of renal renin by a protein plasma fraction: a novel enzymatic mechanism. 865 95

A method for the localization of activities of proteases using substrates with 7-amino-3-trifluoromethylcoumarine (AFC) leaving group is described. 0.1 ml of 5-20 mMol solution of the respective substrate (Gly-Pro-AFC, Ala-Pro-AFC, Z-Ala-Arg-Arg-AFC, Z-Gly-Arg-Arg-AFC, Z-Gly-Gly-Arg-AFC, D-Val-Leu-Lys-AFC) in dimethylsulfoxide or dimethylformamide was added to 0.9 ml of 0.1 M Tris-HCl buffer, pH 7.4-7.8 or 0.1 M cacodylate buffer, pH 5-5.5. In the case of Z-Ala-Arg-Arg-AFC (cathepsin B substrate) 15 mM EDTA and 12 mM dithiothreitol were added. 7 mM amiloride or 2 mg/1 ml aprotinin were used as inhibitors with Z-Gly-Gly-Arg-AFC (urokinase substrate) and with D-Val-Leu-Lys-AFC (plasmin substrate). Substrate solutions were mixed with an equal amount of 2% agar solution in distilled water or in the respective buffer the pH of which was adjusted according to the pH optimum of the enzyme to be demonstrated. The agar solution was kept in a water bath at a temperature of 50-60 degrees C. After careful mixing, the substrate solution in agar was poured into a cylindrical vessel closed with a semipermeable membrane (Nephrophan) on which unfixed cryostat sections were mounted. 1-5 mM AFC solution in dimethylsulfoxide or dimethylformamide instead of the substrate was used as the control. Quenched samples of rat kidney and jejunum, biopsies of human jejunal mucosa, and of colorectal and uterine tumors were employed for the preparation of sections. After gelification of the medium in a refrigerator the vessels with sections were incubated in the dark at 37 degrees C for 0.5-several h. The reaction was controlled in a fluorescence microscope with an epiillumination adjusted to the FITC fluorescence and documented. A yellowish green fluorescence depicts sites where AFC was set free (sites with enzyme activity). When the reaction reached the required intensity the membranes were cut off, transferred to glass slides, mounted in glycerol, observed and photographed immediately (due to the solubility of AFC in glycerol). An acceptable cellular localization was achieved. The method with AFC substrates can be recommended for comparative biochemical and histochemical studies of proteases using the same substrate and for cases in which no other reliable procedure for the localization of the respective enzyme activity is available (e.g. urokinase, plasmin).
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PMID:The use of substrates with 7-amino-3-trifluoromethylcoumarine (AFC) leaving group in the localization of protease activities in situ. 873 6

Collagens of most connective tissues are subject to continuous remodelling and turnover, a phenomenon which occurs under both physiological and pathological conditions. Degradation of these proteins involves participation of a variety of proteolytic enzymes including members of the following proteinase classes: matrix metalloproteinases (e.g. collagenase, gelatinase and stromelysin), cysteine proteinases (e.g. cathepsin B and L) and serine proteinases (e.g. plasmin and plasminogen activator). Convincing evidence is available indicating a pivotal role for matrix metalloproteinases, in particular collagenase, in the degradation of collagen under conditions of rapid remodelling, e.g. inflammation and involution of the uterus. Under steady state conditions, such as during turnover of soft connective tissues, involvement of collagenase has yet to be demonstrated. Under these circumstances collagen degradation is likely to take place particularly within the lysosomal apparatus after phagocytosis of the fibrils. We propose that this process involves the following steps: (i) recognition of the fibril by membrane-bound receptors (integrins?), (ii) segregation of the fibril, (iii) partial digestion of the fibril and/or its surrounding non-collagenous proteins by matrix metalloproteinases (possibly gelatinase), and finally (iv) lysosomal digestion by cysteine proteinases, such as cathepsin B and/or L. Modulation of this pathway is carried out under the influence of growth factors and cytokines, including transforming growth factor beta and interleukin 1 alpha.
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PMID:Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling. 876 55


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