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 levels of kallikrein and collagenase in synovial fluid from rheumatoid arthritis (RA) patients were examined and the role of kallikrein in procollagenase activation is discussed. Both prekallikrein and active kallikrein in synovial fluid from patients with RA were significantly elevated when compared to synovial fluid from patients with osteoarthritis (OA). In RA synovial fluid, the ratio of the active form to total kallikrein was also higher than that in OA synovial fluid. Both active collagenase and the alpha 2-macroglobulin (alpha 2M)-collagenase complex in RA synovial fluid were higher than in OA synovial fluid. A partial correlation (r = 0.58) between active kallikrein and total collagenase (active and alpha 2M-collagenase complex) was observed in RA synovial fluid. These observations indicate that both kallikrein and collagenase are associated with the destruction of cartilage, but the role of kallikrein in procollagenase activation was not fully clarified.
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PMID:Kallikrein in synovial fluid with rheumatoid arthritis. 303 90

The filtration pattern of Ophiophagus hannah venom on Sephadex G-75 shows several peaks. The first peak, S1, includes high molecular weight proteins and contains the hemorrhagic and proteolytic activities. The proteolytic fractions overlap the hemorrhagic fractions, but are not identical with them. The crude venom and the high molecular weight peak have caseinase, benzoyl-L-arginine ethyl ester hydrolase and kallikrein-like activities, but not collagenase, gelatinase, thrombin, plasmin or urokinase-like activities. The hemorrhagin of Ophiophagus hannah shows species specific differences in its hemorrhagic effects: it causes hemorrhages in rabbits and hares (Lagomorpha), but not in rats, mice or guinea-pigs (Rodentia).
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PMID:Species specific sensitivity towards the hemorrhagin of Ophiophagus hannah (Elapidae). 330 49

We have identified a tissue-kallikrein-binding protein in human serum and in the serum-free culture media from human lung fibroblasts (WI-38) and rodent neuroblastoma X glioma hybrid cells (NG108-15). Purified and 125I-labelled tissue kallikrein and human serum form an approximately 92,000-Mr SDS-stable complex. The relative quantity of this complex-formation is measured by densitometric scanning of autoradiograms. Complex-formation between tissue kallikrein and the serum binding protein was time-dependent and detectable after 5 min incubation at 37 degrees C, with half-maximal binding at 28 min. Binding of 125I-kallikrein to kallikrein-binding protein is temperature-dependent and can be inhibited by heparin or excess unlabelled tissue kallikrein but not by plasma kallikrein, collagenase, thrombin, urokinase, alpha 1-antitrypsin or kininogens. The kallikrein-binding protein is acid- and heat-labile, as pretreatment of sera at pH 3.0 or at 60 degrees C for 30 min diminishes complex-formation. However, the formed complexes are stable to acid or 1 M-hydroxylamine treatment and can only be partially dissociated with 10 mM-NaOH. When kallikrein was inhibited by the active-site-labelling reagents phenylmethanesulphonyl fluoride or D-Phe-D-Phe-L-Arg-CH2Cl no complex-formation was observed. An endogenous approximately 92,000-Mr kallikrein-kallikrein-binding protein complex was isolated from normal human serum by using a human tissue kallikrein-agarose affinity column. These complexes were recognized by anti-(human tissue kallikrein) antibodies, but not by anti-alpha 1-antitrypsin serum, in Western-blot analyses. The results show that the kallikrein-binding protein is distinct from alpha 1-antitrypsin and is not identifiable with any of the well-characterized plasma proteinase inhibitors such as alpha 2-macroglobulin, inter-alpha-trypsin inhibitor, C1-inactivator or antithrombin III. The functional role of this kallikrein-binding protein and its impact on kallikrein activity or metabolism in vivo remain to be investigated.
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PMID:Identification of a new tissue-kallikrein-binding protein. 364 93

1. Trypsin digestion of perchloric acid precipitated horse plasma yielded polypeptides with inhibitory properties for trypsin, chymotrypsin and, to a small extent, kallikrein. 2. The Mr of the inhibitory polypeptides were 73,000 and 24,000. 3. The number, enzyme specificity and Mr of the inhibitory polypeptides differed from the values known for the human being. 4. The inhibitory polypeptides were purified by affinity chromatography on Sepharose-trypsin and by gel filtration through Sephadex G-75. 5. Protease inhibitory polypeptides were generated in the same manner by chymotrypsin, elastase, proteinase K, pronase, collagenase, papain and subtilisin. 6. The number and electrophoretic migration of the inhibitory polypeptides obtained with the different enzymes were variable. 7. The enzyme specificity was constant since all polypeptides inhibited only trypsin, chymotrypsin and kallikrein to a small extent. 8. None of the inhibitory polypeptides were immunologically related to native plasma proteins or plasma protease inhibitors.
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PMID:Acid-stable protease inhibiting polypeptides formed from denatured horse plasma by proteolysis. 367 4

It has been previously observed that collagen destruction occurs in the vicinity of immune complexes present in articular cartilages of patients with rheumatoid arthritis. When IgG is covalently linked to Sepharose it behaves as if it has reacted with an antigen to form an immune complex, in that it binds the complement component C1 from human serum. Other serum components also interact with this matrix, though their interaction may not be specific for IgG. Two of these components were shown to possess proteolytic activity, one being kallikrein and the other having the properties of plasmin. Both of the activities could activate latent human collagenase. Whilst the binding of the plasmin activity is probably nonspecific, the binding of the kallikrein activity may be selective for IgG (although it is not certain whether this binding is direct or indirect via another molecule). These results therefore suggest that active proteinases such as plasma kallikrein may be selectively concentrated on immune complexes in vivo, where they may locally activate latent proteinases such as collagenase thereby initiating tissue destruction.
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PMID:Activation of latent collagenase by serum proteinases that interact with immobilized immunoglobulin G. 609 Dec 34

Viable dispersed cell preparations of rat submandibular gland were obtained by a tissue-dissociation procedure using collagenase and gentle mechanical force. The cells released kallikrein-like esterase in a time- and calcium-dependent manner in response to noradrenaline (10 microM) at 30 degrees C. The net loss of kallikrein-like esterase content from the dispersed cells corresponded with the increase in kallikrein-like esterase activity in the suspending medium at all concentrations of noradrenaline. These results indicate the viability and functional integrity of this dispersed cell preparation of rat submandibular gland. alpha-Adrenoceptor agonists such as noradrenaline stimulated kallikrein-like esterase and tonin release in a dose-dependent manner, whereas the beta-adrenoceptor agonist isoprenaline and cholinoceptor agonist methacoline were both inactive. Noradrenaline-induced release of kallikrein-like esterase and tonin were completely blocked by prior addition of the alpha-adrenoceptor antagonist, phenoxybenzamine. It is concluded that the secretion of kallikrein-like esterase and tonin in rat submandibular gland is mediated only via stimulation of alpha-adrenoceptors.
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PMID:Release of kallikrein-like esterase and tonin from dispersed cells of the rat submandibular gland. 614 66

A randomized controlled trial was performed to assess the effect of intravenous aprotinin (Trasylol) on the healing of experimental colonic anastomoses in the rabbit following a standard left colonic resection anastomosis. Assessment of tensile strength was by means of both bursting pressure and breaking strength. Those animals subjected to bursting pressure assessment received intravenous aprotinin 80 000 KIU (kallikrein inhibitory units) at the time of anaesthesia, and postoperatively 160 000 KIU per day given in divided doses for three days. Control animals received saline placebo. A further group of animals received a lower loading and maintenance aprotinin dose (40 000 KIU and 60 000 KIU per day respectively) with control animals receiving saline. Breaking strength was employed as the means of assessment. The mean bursting pressures were 47.7 +/- 2.9 mmHg and 37.5 +/- 3.4 mmHg for aprotinin and controls respectively (P less than 0.05). The mean difference in collagen content of the anastomosis compared to the resected specimen was +1.25 +/- 0.50 microgram/mg and -1.02 +/- 0.47 microgram/mg for aprotinin and placebo groups (P less than 0.005). The mean breaking strength in the aprotinin group was 169.6 +/- 74.5 g and 110.0 +/- 65.9 g for the saline group (P less than 0.02). The mean difference in collagen content of the anastomosis compared to the resected specimen was +0.95 +/- 0.69 microgram/mg and -1.5 +/- 0.78 microgram/mg for the aprotinin and saline groups respectively (P less than 0.05). The significant elevation of both bursting pressure and breaking strength assessments, with a significant improvement in the collagen content of the anastomoses, may be the result of collagenase inhibition following the use of intravenous aprotinin in the experimental model.
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PMID:Collagenase inhibition in the healing colon. 618 11

Human serum contains enzyme(s) able to degrade serum amyloid A protein (SAA) and amyloid A (AA) fibrils. On the basis of inhibition tests these enzymes are regarded as serine proteases, but further characterization of the enzymes has, however, so far not been done. Chymotrypsin, trypsin, elastase, collagenase and kallikrein, when added to SAA-containing serum, all degraded SAA to peptides within 2 h at 37 degrees C. With the exception of collagenase these enzymes also destroyed the Sirius-Red-binding ability of amyloidotic tissue and that of isolated AA fibrils. Hence, they altered the conformation of the beta-pleated structure and possibly also degraded the fibrils. These results suggest that any of these serine proteases could be responsible of the degradation of SAA in serum. The enzyme concentrations needed to degrade amyloid fibrils, however, were much higher than normally found in serum. Thus, it is unlikely that the amyloid-fibril-degrading activity in serum could be due to any of these enzymes.
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PMID:Do serine proteases degrade amyloid A fibrils? 619 37

mRNA extracted from rabbit synovial fibroblasts which had been induced to produce large amounts of collagenase (EC 3.4.23.7) by urate crystals was translated in a cell-free wheat germ system. Collagenase was identified by immunoprecipitation using mono-specific antibody to rabbit synovial collagenase. In the absence of microsomal membranes, a single precursor with Mr = 59,000 was synthesized. This polypeptide was susceptible to proteolytic degradation. In the presence of canine pancreatic microsomes, the nascent protein was processed to a polypeptide with Mr = 57,000 (identical in mobility on sodium dodecyl sulfate-gel electrophoresis to the major latent collagenase secreted from cells) and was protected from tryptic digestion unless a detergent was used to disrupt the membranes. In addition to Mr = 57,000 material, cells secreted immunologically reactive latent collagenase with Mr = 61,000. High molecular weight collagenase was separated from Mr = 57,000 species by binding to concanavalin a-Sepharose, suggesting that this enzyme was a product of post-translational glycosylation. Both latent enzymes were activated by trypsin and human plasma kallikrein to Mr = 45,000 and 49,000. The evidence indicates that rabbit synovial fibroblast collagenase is synthesized and secreted as a single polypeptide zymogen, not as an enzyme-inhibitor complex.
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PMID:A precursor form of latent collagenase produced in a cell-free system with mRNA from rabbit synovial cells. 627 68

Rheumatoid synovial fluid contains an activator of latent collagenase from culture medium of pig synovium. The activator was purified by gel chromatography on Ultrogel AcA 44 and affinity chromatography on soybean trypsin inhibitor coupled to Sepharose 4B. The purified material was homogeneous on SDS-polyacrylamide gel electrophoresis with Mr 88 000. The activator had limited proteolytic activity against azo-casein, but showed amidase activity on Pro-Phe-Arg-NMec, Z-Phe-Arg-NMec, D-Val-Leu-Arg-NPhNO2 and D-Pro-Phe-Arg-NPhNO2, with an optimum at pH 8.0. Activity was completely inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, leupeptin and Pro-Phe-Arg-CH2Cl, whereas lima bean trypsin inhibitor, Tos-Lys-CH2Cl, a specific inhibitor of factor XIIa from maize, EDTA and iodoacetate were not inhibitory. These properties of the activator suggested that it might be plasma kallikrein (EC 3.4.21.34), and the possibility was further examined. The activator was treated with [3H]diisopropyl fluorophosphate, and run in SDS-polyacrylamide gel electrophoresis with reduction; a radioautograph of the gel showed a pair of [3H]diisopropyl phosphoryl-labelled bands (Mr 36 000 and 34 000) identical to those obtained with authentic plasma kallikrein. Double immunodiffusion with monospecific antiserum against human plasma kallikrein confirmed the identification. This is the first demonstration of collagenase-activating activity of plasma kallikrein, and raises the possibility that activation of prokallikrein in the inflamed joint space may contribute to the disease process not only by the production of bradykinin, but also by activating latent collagenase.
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PMID:Identification of plasma kallikrein as an activator of latent collagenase in rheumatoid synovial fluid. 627 61


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