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)

Two new human cell lines, RCM-1 and CoCM-1, have been established from primary colorectal adenocarcinomas. Both cell lines were unique in that the cultures secreted trypsin inhibitors in vitro. The activities of these inhibitors were accumulated in serum-free media of both cell lines over a period of several days. Two inhibitors (PI-1 and PI-2) were isolated from serum-free conditioned medium in which RCM-1 was grown by anion-exchange and gel filtration high-performance liquid chromatography. PI-1 inhibited trypsin and chymotrypsin strongly, and pancreatic elastase weakly. Its molecular weight was about 57 kilodaltons (Kd) as determined by gel filtration chromatography. It cross-reacted with the antiserum elicited against human alpha 1-antitrypsin in double immunodiffusion. PI-1 corresponding to alpha 1-antitrypsin was also demonstrated immunohistochemically in both cell lines. PI-2 inhibited trypsin strongly, and chymotrypsin, kallikrein and plasmin weakly. It had higher molecular weight (200-300 Kd) than that of PI-1, and did not cross-react with antisera against human alpha 1-antitrypsin, alpha 2-macroglobulin, alpha 1-antichymotrypsin, alpha 2-plasmin inhibitor, inter-alpha-trypsin inhibitor and urinary trypsin inhibitor. RCM-1 and CoCM-1 are the first colorectal adenocarcinoma cell lines that secrete functionally active trypsin inhibitors, including alpha 1-antitrypsin in vitro, and are useful for the study of tumor-cell derived proteinase inhibitors.
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PMID:New human colorectal carcinoma cell lines that secrete proteinase inhibitors in vitro. 257 Apr 82

We have isolated three cDNA clones for human alpha 2-plasmin inhibitor (alpha 2-PI). Two clones are from human hepatoma cell line, Hep G2, and cover the entire protein coding region plus the 3'-flanking region up to the poly(A) sequence, and the other clone is from human liver and contains the carboxyl-terminal half. The total length of the cDNAs is 2.29 kb, corresponding to more than 95% of the full-length mRNA. alpha 2-PI seems to consist of 452 amino acid residues plus 39 amino acid residues for the signal peptide. The amino acid sequence shows 23 to 28% homology to those of five other protease inhibitors, plasminogen activator inhibitor (PAI), protein C inhibitor (PCI), alpha 1-antitrypsin (alpha 1-AT), antithrombin III (AT III), and alpha 1-antichymotrypsin (alpha 1-AC). alpha 2-PI seems to be the most distantly related among these inhibitors. Comparison of the phylogenetic trees of proteases and their inhibitors indicates that four proteases, namely elastase (or trypsin), chymotrypsin, plasminogen activator, and thrombin, may have evolved concurrently with the corresponding inhibitors. However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates. The data suggest that alpha 2-PI may originally have inhibited some protease other than plasmin, and protein C may have had an inhibitor different from the present one early in its evolutionary history.
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PMID:Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence. 283 Feb 48

In our previous research, we found that the level of the plasminogen activity in the plasma from Duchenne-type patients with progressive muscular dystrophy was higher than of the normal boys, though the level of the plasmin inhibitors was lower. Therefore, in the present study, we investigated the differences in the fractions of plasmin inhibitors. The subjects were nine patients (the average age being 17.1 years) who had been diagnosed, by clinical and biochemical tests, as having PMD; serving as controls were normal boys (the average age being 15 years), the patients' mothers, and the mothers of the normal boys. The plasmin inhibitors were separated from plasma using lysine-Sepharose columns according to the method of Urita et al. The determination was performed based on the method of Aoyagi et al. and an immunoreactive assay. The results were as follows: (1) No significant differences were seen between patients with PMD and control subjects with respect to either alpha 1-antichymotrypsin, antithrombin III, and alpha 1-antitrypsin or alpha 2-macroglobulin and inter-alpha-trypsin inhibitors. These results suggested that the low level of plasmin inhibitors in patients was due to the low activity of the C1 inactivator. (2) The patients with PMD showed lower values than the normal boys in the levels of C1 inactivator in plasma; similarly, the mothers of these patients showed lower values than the normal mothers.
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PMID:Plasma plasmin inhibitors in Duchenne-type progressive muscular dystrophy. 316 Mar 43

Proteinases are classified into four groups according to their catalytic mechanisms: the serine, cysteine (thiol), aspartic (carboxyl), and metallo-proteinases. Neutrophil granulocytes contain a variety of neutral proteinases and two acid proteinases. Lysosomal proteinases are released from cells during phagocytosis, cell death, or exposure to antigen-antibody complexes, complement factors, and toxins. Under pathological conditions, massive proteinase release may cause tissue injury and degradation of plasma proteins. Plasma proteolytic activity is controlled by inhibitors of blood systems (antithrombin III, C1 inhibitor, and plasmin inhibitor) and by inhibitors against proteinases of various body cells (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, beta 1-collagenase inhibitor, and inter-alpha-trypsin inhibitor). Intracellular proteinases are controlled by different cytosolic inhibitors. In hypercatabolic states (septicemia, trauma, burns), the concentrations of many plasma proteins, including proteinase inhibitors, are decreased. Kallikrein-kinin, complement, and fibrinolytic systems may be activated, probably due to enhanced proteinase activity. In acute renal failure, there is a release of granulocyte neutral proteinases. The plasma concentration of the elastase-alpha 1-proteinase inhibitor complex is simultaneously increased. Granulocytes of chronically uremic patients treated with diet or regular dialysis have a slightly to markedly reduced proteinase content as compared with normal controls. There is a dramatic rise of the plasma elastase alpha 1-proteinase inhibitor complex during hemodialysis treatment.
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PMID:Proteolytic enzymes and catabolism: enhanced release of granulocyte proteinases in uremic intoxication and during hemodialysis. 637 17

Two major human plasma proteinase inhibitors, C1-inhibitor and alpha 1-antichymotrypsin, were enzymatically inactivated by Pseudomonas aeruginosa elastase and proteinase. Incubation of C1-inhibitor with the Pseudomonas enzymes at inhibitor/enzyme molar ratios of 1000:1 (elastase) or 22:1 (proteinase) resulted in cleavage of the 104 kDa intact inhibitor to an 89 kDa intermediate which retained full inhibitory activity against plasmin and plasma kallikrein. The intermediate was then cleaved to an 83 kDa inactive product. The initial non-inactivating cleavage of C1-inhibitor occurred in a region of the molecule readily accessible to limited proteolysis by both enzymes. The inactivating cleavage, however, occurred more readily with the elastase. alpha 1-Antichymotrypsin was inactivated by P. aeruginosa proteinase and elastase by limited proteolysis at inhibitor/enzyme molar ratios of 14 000:1. The 64 kDa intact inhibitor was cleaved to form an inactive 60 kDa product, and a low molecular mass peptide fragment was observed. No stable enzyme-inhibitor complexes were detected, and no random proteolysis of the inactivated inhibitors was noted, even after prolonged incubation. Catalytic inactivation of C1-inhibitor and alpha 1-antichymotrypsin by P. aeruginosa proteinase and elastase may contribute to the tissue damage and hemorrhagic lesions which occur during pseudomonal infections.
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PMID:Enzymatic inactivation of human plasma C1-inhibitor and alpha 1-antichymotrypsin by Pseudomonas aeruginosa proteinase and elastase. 643 51

An acid-stable protease inhibitor (AS-PI) has been previously demonstrated in ascitic fluid from patients with ovarian carcinoma. In this study, the AS-PI was further purified using DEAE-cellulose and isoelectric focusing (IEF), and a partial characterization was undertaken. On DEAE-cellulose ion-exchange column chromatography, AS-PI activity was observed in both adsorbed and non-adsorbed fractions. The former represented the main AS-PI peak. By IEF, the respective pI values were 1.6 and 4.5. By gel filtration, the molecular weight of the main (adsorbed fraction) AS-PI was 78 000. This AS-PI strongly inhibited trypsin and to a lesser extent chymotrypsin, but exerted no inhibitory effect on plasmin. It slightly inhibited SH proteases such as papain and ficin. Immunologically, AS-PI was distinct from alpha 1-antitrypsin, alpha 1-antichymotrypsin, inter-alpha-trypsin inhibitor, antithrombin III, C1-inactivator, alpha 2-macroglobulin and alpha 2-plasmin inhibitor. The main AS-PI reacted with and was neutralized by antiurinary trypsin inhibitor serum, and on immunoelectrophoresis, had a mobility slightly cathodal to serum albumin.
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PMID:Further purification and characterization of acid-stable protease inhibitor from ascites of an ovarian carcinoma patient. 643 8

Serine proteinase inhibitors play a major role in the turnover of connective tissues. In this study, we isolated and determined partial amino-terminal amino acid sequence of trypsin/elastase/plasmin inhibitors (M(r) 33,000 and 31,000) from the extracellular matrix of SV40-transformed human skin fibroblasts. The antitrypsin activity of the inhibitors was monitored by substrate reverse zymography. Polyclonal antisera to alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-antiplasmin, inter-alpha-trypsin inhibitor, plasminogen activator inhibitors-1 and -2, and a monoclonal antibody to protease nexin-1 did not label the 33-, 31-, and 27-kDa inhibitors. A computer search for amino acid sequence homology indicated that the 31-kDa inhibitor is novel. In contrast, the sequence of the 33-kDa inhibitor shared 70 to 90% homology with the amino-terminal sequence of a recently characterized 32-kDa trypsin/tissue factor inhibitor called tissue factor pathway inhibitor-2. The 33- and 31-kDa inhibitors bind to heparin-Sepharose and were recovered from the affinity beads as well as from the t12 FB extracellular matrix with 1 M NaCl. Based on these results, we propose that the extracellular matrix of human mesenchymal cells sequester a family of novel serine proteinase inhibitors.
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PMID:Novel extracellular matrix-associated serine proteinase inhibitors from human skin fibroblasts. 787 99

An inhibitor of pancreatic elastase (EI), which can also inhibit chymotrypsin, and an inhibitor of trypsin (TI), which can also inhibit plasmin, have been isolated from bovine plasma. EI and TI belong to the serpin family of inhibitors. The size of both inhibitors is approx. 60 kDa and they are able to form SDS-stable complexes with proteinases. Curiously, TI dimerizes in the presence of SDS, a feature which has been observed previously only in non-denaturing gels of human alpha 1-antitrypsin (alpha 1PI). EI and TI are glycosylated [16% and 19% (w/w) respectively] and their amino acid compositions are similar to those of other plasma serpins. Neither EI nor TI is the equivalent of bovine alpha 1PI, as revealed by partial sequence analysis of their N-termini and reactive sites. Rather, both inhibitors appear to be related to human alpha 1-antichymotrypsin. Inhibition of pancreatic elastase and chymotrypsin by EI occurs with a kass. approximately 10(5) M-1.s-1. TI inhibits trypsin with a kass. approximately 10(5) M-1.s-1. Plasmin is inhibited by TI with a kass. approximately 10(3) M-1.s-1. The values of the kinetic constants are similar to those determined for the well-studied human serpins. Antibodies to EI and TI reveal a set of four antigenically related proteins of similar size in plasma. In addition, they detect the same set of proteins in milk. The inhibitors isolated from milk are identical to EI and TI from plasma. EI could control the activity of chymotrypsin-like proteinases in milk. In contrast, no target proteinases of TI in milk can be suggested.
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PMID:Characterization of two serpins from bovine plasma and milk. 798 Mar 96

Serpins represent a diverse class of endogenous protease inhibitors that regulate important biological functions. In consideration of the importance of regulated proteolysis within secretory vesicles for the production of peptide hormones and neurotransmitters, this study revealed the molecular identity of a novel serpin, endopin 1, that is localized to neurosecretory vesicles of neuropeptide-containing chromaffin cells (chromaffin granules). Endopin 1 of 68-70 kDa was present within isolated chromaffin granules. Stimulated cosecretion of endopin 1 with chromaffin granule components, [Met]enkephalin and a cysteine protease known as "prohormone thiol protease," demonstrated localization of endopin 1 to functional secretory vesicles. Punctate, discrete immunofluorescence cellular localization of endopin 1 in chromaffin cells was consistent with its secretory vesicle localization. Endopin 1 contains a unique reactive site loop with Arg as the predicted P1 residue, suggesting inhibition of basic residue-cleaving proteases; indeed, trypsin was potently inhibited (K(i(app)) of 5 nM), and plasmin was moderately inhibited. Although endopin 1 possesses homology with alpha(1)-antichymotrypsin, chymotrypsin was not inhibited. Moreover, endopin 1 inhibited the chromaffin granule prohormone thiol protease (involved in proenkephalin processing). These results suggest a role for the novel serpin, endopin 1, in regulating basic residue-cleaving proteases within neurosecretory vesicles of chromaffin cells.
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PMID:Molecular cloning of endopin 1, a novel serpin localized to neurosecretory vesicles of chromaffin cells. Inhibition of basic residue-cleaving proteases by endopin 1. 1056 88

Peptides derived from proteolytic degradation of the amyloid precursor protein, e.g., amyloid beta (A beta), are considered to be central to the pathology of Alzheimer's disease (AD). Soluble A beta is present in measurable concentrations in cerebrospinal fluid and blood. There are indications that soluble A beta present in circulation can cross the blood-brain barrier via transcytosis mediated by brain capillary endothelial cells. It implies that A beta originating from circulation may contribute to vascular and parenchymal A beta deposition in AD. Enhancing of A beta catabolism mediated by proteolytic degradation or receptor-mediated endocytosis could be a key mechanism to maintain low concentrations of soluble A beta. To launch A beta clearance we have exploited the A beta-degrading activity of diverse alpha 2-macroglobulin (alpha 2-M)-proteinase complexes. Complexes with trypsin, alpha-chymotrypsin, and bromelain strongly degrade (125)I-A beta 1--42 whereas complexes with endogenous proteinases, e.g., plasmin and prostate-specific antigen, were not effective. A beta degradation by the complexes was not inhibited by alpha 1-antichymotrypsin and soybean trypsin inhibitor which normally would inactivate the free serine proteinases. A prerequisite for A beta degradation is its binding to specific binding sites in alpha 2-M that may direct A beta to the active site of the caged proteinase. Ex vivo, enhanced degradation of (125)I-A beta 1--42 in blood could be achieved upon oral administration of high doses of proteinases to volunteers. These results suggest that up-regulation of A beta catabolism could probably reduce the risk of developing AD by preventing A beta accumulation in brain and vasculature.
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PMID:Alpha 2-macroglobulin-mediated degradation of amyloid beta 1--42: a mechanism to enhance amyloid beta catabolism. 1116 27


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