Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The low molecular weight bronchial protease inhibitor isolated from purulent bronchial secretions of man was shown to be a potent inhibitor of the elastase from human granulocytes. At a molar ratio of 1:1, the inhibitor prevented elastase digestion of insoluble elastin and soluble elastin, and blocked the hydrolysis of t-BOC-L-alanine-p-nitrophenyl ester. The collagenolytic activity of granulocyte collagenase was not inhibited by the bronchial inhibitor. Antisera were raised in rabbits for the isolation of specific IgG fractions in order to localize and quantitate the inhibitor. 125I-labelled inhibitor was used to study enzyme interactions further by gel filtration. These studies demonstrated that the bronchial inhibitor formed firm complexes with granulocyte elastase but did not form complexes with granulocyte collagenase.
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PMID:Inhibition of elastase from granulocytes by the low molecular weight bronchial protease inhibitor. 18 83

In epidermolysis hereditaria bullosa dystrophica increased collagenase activity can be detected and seems to be one of the pathogenetic mechanisms of this disease. Neither the origin nor the mechanism of increased collagenolysis is known. Whether the cause of the enzymatic imbalance is the increased collagenase production or decreased collagenase-inhibitor activity cannot be decided. Factors of decreased protease inhibitor activity could be the quantitative or qualitative defect or the inactivation of the inhibitor. Clear, sterile vesicular fluid was incubated with alpha-1-antitrypsin, which is known to inhibit collagenase. By means of an immunoelectrophoretic method the cleaving of the inhibitor into two antigenic split products was found. We suggest that this might be responsible for the increased collagenolysis in this form of epidermolysis.
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PMID:[Vesicular fluid of hereditary bullous dystrophic epidermolysis splits alpha 1-antitrypsin]. 19 57

1. The uptake of 125I-labelled high density lipoproteins (HDL) in various organs of the rat was determined after an intravenous injection. The uptake of 125I-labelled polyvinylpyrrolidone in the same organs was determined in order to assess uptake by fluid endocytosis. The uptake/organ was highest for the liver. The adrenals showed the highest uptake/unit weight of the organs studied. The liver, the kidneys and the spleen showed comparable values for uptake/g of tissue. The uptake of 125I-labelled HDL exceeded by far that of 125I-labelled polyvinylpyrrolidone in the liver, the kidneys, the spleen and the adrenals, indicating that the uptake of 125I-labelled HDL was mediated by adsorptive endocytosis. 2. The in vivo uptake of 125I-labelled HDL was determined in purified hepatocytes and non-parenchymal cells prepared by collagenase perfusion of livers from animals after intravenous injections of 125I-labelled HDL. When expressed per cell, the hepatocytes and the non-parenchymal liver cells took up about the same amount of 125I-labelled HDL. 3. The in vitro uptake and degradation of 125I-labelled HDL in isolated rat hepatocytes was studied. The uptake at increasing concentrations of 125I-labelled HDL was saturable indicating uptake mediated through binding sites. 125I-labelled HDL were easily degraded by contaminating proteases from the perfusate. 4. Subcellular fractionation by isopycnic centrifugation indicated that the accumulation of 125I-labelled HDL did not take place in the lysosomes, but rather on the plasma membrane and possibly in the endosomes (phagosomes). 5. 125I-labelled HDL were internalized into the cells and degraded in the lysosomes. Leupetin and chloroquine, inhibitors of the lysosomal function effectively inhibited the formation of 125I-labelled acid-soluble radioactivity by the cells. Chloroquine, but not the protease inhibitor leupeptin, reduced the hydrolysis of the cholesteryl ester moiety of HDL.
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PMID:Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro. 22 59

The pericellular matrix of human fibroblast cultures was isolated, using sequential extraction with sodium deoxycholate and hypotonic buffer in the presence of protease inhibitor. The matrix attached to the growth substratum had a "sackcloth-like" structure as seen by phase contrast, immunofluorescence, and scanning electron microscopy, and it had a vaguely filamentous ultrastructure similar to that seen in intact cell layers. The matrix consisted of hyaluronic acid and heparan sulfate as the major glycosaminoglycan components and fibronectin and procollagen as major polypeptides as shown by metabolic labeling, gel electrophoresis, immunofluorescence, and collagenase digestion. This pericellular matrix can be regarded as an in vitro equivalent of the loose connective tissue matrix.
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PMID:Isolation of the pericellular matrix of human fibroblast cultures. 38 22

Studies on the effects of bovine aorta extracts on endothelial and smooth muscle cells cultured from the same tissue indicate they contain at least four separate molecular species capable of inhibiting cell growth. Two, heparin and a recently characterized dermatan sulfate-chondroitin sulfate proteoglycan, are large polyanions and inhibit the growth of both smooth muscle and endothelial cells, but require large amounts to induce this effect. The other two are low molecular weight molecules which inhibit only the growth of endothelial cells, one of which is a protease inhibitor which has been purified to homogeneity. The fourth and most potent is an as yet unidentified fraction distinguishable from the protease inhibitor. Heparin, as reported by others, and the proteoglycan also enhance collagenase activity. It would therefore appear that aorta contains several molecular species which have the potential to affect both invasive and proliferative processes.
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PMID:Growth regulators in connective tissues. II. Evidence for the presence of several growth inhibitors in aortic extracts. 53 30

Tryptase from human mast cells has been shown (in vitro) to catalyze the destruction of fibrinogen and high-molecular-weight kininogen as well as the activation of C3a and collagenase. Although large amounts of tryptase are released in tissues by degranulating mast cells and levels as high as 1000 ng/ml have been measured in the circulation following systemic anaphylaxis, no specific physiologic inhibitor has yet been found for the protease. The current work tests several more inhibitors for their effects on tryptase and examines any effect of tryptase on these inhibitors. First, antileukoprotease and low-molecular-weight elastase inhibitor from human lung and hirudin and antithrombin III had no effect on tryptase activity in vitro. Second, the possibility that tryptase, being insensitive to the effects of inhibitors, might instead destroy them was also considered. Tryptase failed to cleave and inactivate antileukoprotease, low-molecular-weight elastase inhibitor, alpha 1 protease inhibitor, alpha 2 macroglobulin, and antithrombin III. Third, based on the knowledge that tryptase stability is regulated by its interaction with heparin, antithrombin III was used as a model heparin-binding protein to demonstrate that a protein competitor for heparin-binding sites, presumably by displacement of tryptase, destabilizes this enzyme. Conversely, tryptase, in excess, blocked the binding of antithrombin III to heparin, thereby attenuating the heparin-mediated inhibition of thrombin by antithrombin III.
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PMID:Interactions of human mast cell tryptase with biological protease inhibitors. 168 95

In schistosomiasis mansoni the parasite egg-induced granulomatous tissue inflammations resolve by fibrosis. Intralesional collagen synthesis and deposition are influenced by collagenase, elastase activity that is diminished at the chronic stage of the disease. To determine the cause of diminished neutral protease activity, the authors determined levels of the antiprotease/alpha 2-macroglobulin (alpha 2M) and alpha 1-protease inhibitor (alpha 1Pi) in extracts or secretions of liver granulomas of infected mice. By ELISA, both antiproteases were detected in granuloma-derived substances, as well as supernatants of cultured, adherent granuloma macrophages. In all samples, alpha 2M was the predominant inhibitor. Antiprotease levels were similar in granuloma-derived samples obtained from acutely and chronically infected mice. However, supernatants of cultured adherent macrophages isolated from granulomas of mice with acute infection contained levels of protease inhibitors several times higher than those of similar preparations obtained from chronically infected animals. Gel filtration of samples on Sephacryl S-200 columns did not separate collagenase and elastase from protease inhibitors. By chromatofocusing, a few inhibitor-free collagenase as well as enzyme-free alpha 2M and alpha 1Pi-active peaks were eluted. The bulk of the material that eluted at the acidic region contained protease-antiprotease activity indicating the presence of enzyme-inhibitor complexes. The intragranulomatous presence of antiproteases complexed with protease enzymes emphasizes their importance in the possible enhancement of fibrosis.
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PMID:Detection of alpha 2-macroglobulin, alpha 1-protease inhibitor, and neutral protease-antiprotease complexes within liver granulomas of Schistosoma mansoni-infected mice. 244 83

A simple and inexpensive procedure is described which allows reproducibly the isolation of rat pancreatic acinar cells. Using only small quantities of commercially available collagenase without addition of any further protease, a cell population consisting of about 95% of acinar cells can be obtained within about 95 min. Cell yield is 40% as calculated on a dry weight basis. Enzyme activities measured within final suspensions of isolated cells are: amylase, 1.17 +/- 0.27 amylase units.(mg d.w.)-1; lipase, 23.78 +/- 6.02 nkat.(mg d.w.)-1 and alanine aminotransferase, 0.895 +/- 0.236 nkat.(mg d.w.)-1. Isolated cells are morphologically intact as seen by electron microscopy and retain their viability for more than 3 h, even when incubated at 37 degrees C without any substrate and protease inhibitor, as revealed by their ability to exclude trypen blue. Therefore, acinar cells isolated in this manner may prove useful for investigations at cellular level into pathogenetic mechanisms underlying pancreatic diseases.
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PMID:An optimized procedure for isolation of rat pancreatic acinar cells. 246 96

Hedgehog plasma was separated by gel filtration on Sephacryl S-200, the fractions resolved by electrophoresis and the electrophoretograms characterized for collagenase, papain and plasmin inhibiting activities with the high mol. wt substrate casein. The three inhibitors previously identified as alpha 2-, alpha 2-beta- and beta-macroglobulins were found to inhibit all three proteases. These were the only collagenase inhibitors found in plasma. Hedgehog alpha 2-chymotrypsin inhibitor and beta-protease inhibitor were both found to also inhibit papain. Three new inhibitors specific for papain (gamma-, alpha 2- and alpha 1-cysteine protease inhibitors) and one for plasmin (alpha 2-antiplasmin) were also found, bringing the number of protease inhibitors in hedgehog plasma to 14. Immunological cross-reactivity as studied by immunoelectrophoresis showed homology between hedgehog alpha 2-macroglobulin and rat murinoglobulin I and between hedgehog alpha 2-antithrombin and rat antithrombin III.
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PMID:Further studies of plasma protease inhibitors in the hedgehog, Erinaceus europaeus; collagenase, papain and plasmin inhibitors. 288 40

Recently we reported that a kind of serine protease, SH protease, and collagenase might be involved in blister formation and, furthermore, that the cooperative action of these three proteases was essential for blister formation in recessive dystrophic epidermolysis bullosa. In this study we examined the inhibitory effect of clinically usable serine protease inhibitors for blister formation in organ culture and in clinical trials of recessive dystrophic epidermolysis bullosa patients. Camostat mesylate, a synthetic serine protease inhibitor that is available for the treatment of chronic pancreatitis, demonstrated a striking effect of inhibiting blistering in organ culture of normal human skin with recessive dystrophic epidermolysis bullosa blister fluids. Subsequently we administered camostat mesylate by topical application to four patients with recessive dystrophic epidermolysis bullosa to assess its ability to reduce blistering. Therapeutic response was favorable; a significant effect in decreasing the number of blisters was observed in three of four patients. These findings actually supported the hypothesis that a kind of serine protease had a close relationship with blistering in recessive dystrophic epidermolysis bullosa and that therapy with a clinically usable protease inhibitor was useful for the treatment of this disease.
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PMID:Protease inhibitor therapy for recessive dystrophic epidermolysis bullosa. In vitro effect and clinical trial with camostat mesylate. 338 39


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