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)

Human mononuclear phagocytes express an array of serine and metal dependent proteinases that are under complex developmental control and are also highly regulated by physiologic and pharmacologic stimuli. Monocytes contain the intracellular serine proteinases, elastase and cathepsin G, but have little metalloproteinase secretory capacity. Macrophages, on the other hand, produce predominantly metalloproteinases. Phorbol induced differentiation of promonocyte-like U937 cells into more mature mononuclear phagocytes results in transcriptional suppression of cathepsin G and temporally delayed onset of collagenase transcription. Mature macrophages upregulate metalloproteinase synthesis in response to lipopolysaccharide and phorbol myristic acetate; expression is downregulated with interferon gamma and dexamethasone. Thus, during the development of the mononuclear phagocyte, stores of serine proteinases are replaced by regulated secretion of metalloproteinases. These alterations may reflect changing roles of these cells in extracellular matrix degradation.
 ...
PMID:Proteinases secreted by human mononuclear phagocytes. 190 75

Latent collagenase has been isolated in pure form from the rheumatoid synovial fluid. The final preparation, activated by trypsin, yielded a collagenase of specific activity 2,227 units/mg. Electrophoresis in sodium dodecyl sulfate polyacrylamide gels revealed a protein doublet of 54 and 50 kDa. Trypsin or HgCl2 activation resulted in disappearance of the doublet and emergence of a new doublet of 47 and 43 kDa. The latent collagenase could also be activated by leucocyte cathepsin G or plasmin. Neither the latent nor the active collagenase from synovial fluid showed any cross-reactivity with the antibodies against leucocyte collagenase. The trypsin activated collagenase degraded collagen type I, II, III giving typical cleavage products but did not degrade type IV and V collagen.
 ...
PMID:Some properties of latent collagenase from human synovial fluid. 196 84

Myocardial extracellular matrix is organized into a complex arrangement of intercellular and pericellular fibres and fibrils that serves as a supporting framework for contracting cells. Recent evidence suggests that changes in ventricular shape and function occurring after ischaemic injury may be related to alterations of this matrix. In this report we describe the rapid and extensive loss of collagen in myocardial infarction produced by ligating the left anterior descending coronary artery of the rat for 1-3 h. The total collagen content in the myocardial infarct zones after 1, 2 and 3 h of ligation was 75 +/- 8%, 65 +/- 7% and 50 +/- 10% respectively (mean +/- S.D.) of that of either the non-infarcted tissue controls or of the same regions in sex- and age-matched normal left ventricles. A marked decrease also occurred in the residual collagens which were not extractable with 6 M-guanidine hydrochloride, suggesting that rapid degradation of insoluble collagen fibres may also occur. The decreased collagen content in the 3 h myocardial infarct coincided with the appearance of several enzyme activities. Collagenase, other neutral proteinase and presumed lysosomal serine proteinase activities were increased by 3, 3 and 2 times the control values respectively. These results suggest that the increased activities of collagenase and other neutral proteinases may be responsible for the rapid degradation of extracellular matrix collagen in myocardial infarct.
 ...
PMID:Collagen degradation in ischaemic rat hearts. 215 82

The processing of precursor interleukin 1 beta (IL1 beta) by elastase, cathepsin G, and collagenase, the major proteases released at sites of inflammation, was investigated using recombinant pro-IL1 beta. Each of these proteases cleaved the 31-kDa inactive precursor to a form similar in size and specific activity (greater than 10(8) units/mg) to the 17-kDa mature protein isolated from activated monocytes. Elastase, collagenase, and cathepsin G cleaved the IL1 beta precursor at distinct sites which are amino-terminal to the monocyte-processing site, Ala-117 (Cameron, P., Lumjuco, G., Rodkey, J., Bennett, C., and Schmidt, J. A. (1985) J. Exp. Med. 162, 790-801). Amino-terminal sequencing of the products of digestion by elastase and cathepsin G determined that resultant active IL1 beta proteins contained an additional 13 or 3 amino acids relative to mature IL1 beta. Synovial fluid collected from patients with inflammatory polyarthritis and bronchoalveolar lavage fluid from patients with sarcoidosis supplied similar processing activity(s). Control fluids from patients who had no symptoms of inflammatory disease did not exhibit processing activity. Lavage fluids that processed precursor IL1 beta were demonstrated to contain cathepsin G and/or elastase activity, whereas controls were negative. Because a significant fraction of IL1 beta may be secreted from monocytes as the inactive 31-kDa precursor (Hazuda, D. J., Lee, J. C., and Young, P. R. (1988) J. Biol. Chem. 263, 8473-8479, Bomford, R., Absull, E., Hughes-Jenkins, C., Simpkin, D., and Schmidt, J. (1987) Immunology 62, 543-549, and Mizel, S. B. (1988) in Cellular and Molecular Aspects of Inflammation Poste, G., and Crooke, S., eds) pp. 75-93, Plenum Publishing Corp., New York), these results suggest that in vivo the IL1 beta precursor can be processed after secretion by any of several proteases released at inflammatory sites.
 ...
PMID:Processing of precursor interleukin 1 beta and inflammatory disease. 215 47

Procollagenase of human polymorphonuclear leucocytes was purified to homogeneity using a rapid and reproducible method. The purification procedure included affinity chromatography on zinc chelate Sepharose, ion exchange chromatography on Q-Sepharose fast flow, followed by affinity chromatography on orange Sepharose and finally a gel-permeation step on Sephacryl S-300. It was shown by SDS/PAGE, under reducing conditions, that the latent collagenase of human polymorphonuclear leucocytes consists of a single polypeptide chain with an apparent relative molecular mass of 85,000. Upon deglycosylation by endoglycosidase F digestion, the apparent relative molecular mass of the procollagenase was reduced to 53,000 which is similar to that of the fibroblast enzyme, and indicates a close relationship between both enzymes. Sequence data were determined by direct automated Edman degradation of the purified polymorphonuclear leucocyte procollagenase. The complete sequence of the propeptide region (residue 1-120) was thereby established. The proteolytic activation of the polymorphonuclear leucocyte procollagenase by various enzymes was investigated by determining the N-terminal sequences of the intermediate and final activated forms. Activation by chymotrypsin and cathepsin G led to the active form (Mr 64,000) by cleaving 79 N-terminal residues from the proenzyme. Trypsin activates in a two-step process. Cleavage of 48 N-terminal residues led to a still latent Mr 70,000 species. The final active form (Mr 65,000) was obtained by splitting off 20 additional N-terminal residues.
 ...
PMID:Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms. 215 79

Elastin was purified from baboon aorta using Achromobacter collagenase and its susceptibility to proteolysis by various enzymes was studied. Human leukocyte elastase (HLE) hydrolysed baboon aortic elastin 8 times faster than human cathepsin G. Bovine chymotrypsin had virtually no activity against this substrate. The kinetic constants V and [S50] of aortic elastin hydrolysis by HLE (0.15 microM) were 0.00286 mg x ml-1 x min-1 and 0.158 mg x ml-1, respectively. One mg of this elastin could be saturated with 5.6 micrograms of HLE. As with elastins isolated from other sources, the hydrolysis of baboon aortic elastin by HLE was highly sensitive to ionic strength, and a biphasic effect was obtained with increasing NaCl concentrations. A nearly 2-fold stimulation of elastolysis was observed at a 0.15M NaCl concentration. Further increase in ionic strength led to a continuous decrease of the rate of elastolysis which paralleled the decrease of adsorption of elastase to baboon aortic elastin. Cathepsin G, but not bovine alpha-chymotrypsin, was able to stimulate the rate of hydrolysis of baboon aortic elastin by HLE. A 1.7 fold stimulation was observed for a 1:1 molar ratio of the two proteinases and rose to 2.1 for a HLE/Cat. G ratio equal to 8.
 ...
PMID:Susceptibility of baboon aorta elastin to proteolysis. 216 85

Conditioned culture medium derived from Interleukin-I alpha-activated human articular chondrocytes contained both collagen- and proteoglycan-degrading activities. Preparations of soluble type I collagen and the cartilage collagens type II, IX, X and XI were all degraded when incubated with the conditioned culture medium at 35 degrees C. Fractionation of the enzymic activities using column chromatography with Ultragel AcA 34 and Heparin-Sepharose allowed the separation and identification of neutral proteinase, collagenolytic and proteoglycan-degrading activities. Eluant fractions which contained type I collagenase activity effectively degraded collagen type II, but these fractions did not correspond precisely with those which degraded collagen types IX, X and XI. These observations indicate that chondrocytes have the potential to produce a conventional interstitial type II collagenase together with other enzymes having some specificity for the minor collagens. Thus IL-1-activated chondrocytes produce a range of collagenolytic and proteoglycan-degrading enzymes which can process most of the structural components of the cartilage matrix.
 ...
PMID:Degradation of cartilage collagens type II, IX, X and XI by enzymes derived from human articular chondrocytes. 217 Aug 28

The asbestos fibers chrysotile and crocidolite cause a dose-dependent release of specific granule collagenase by human polymorphonuclear leukocytes (PMNL). Release of azurophil granule elastase was induced by the asbestos fibers at higher concentrations, suggesting that asbestos fibers primarily cause the release of specific granule contents of human PMNL. Wollastonite, a fibrous silicate mineral, causes a weaker collagenase release and no elastase release. The collagenase was released in inactive, latent form. Carboxymethyl cellulose (CMC), an agent known to blunt chrysotile-induced hemolysis and production of reactive oxygen metabolites by human PMNL, specifically inhibits chrysotile-induced release of collagenase. Chrysotile asbestos was found to bind the PMNL serine proteinase cathepsin G. A role of collagenase release, production of reactive oxygen metabolites and cathepsin G binding by chrysotile for the perpetuation of the asbestos-induced alveolitis is suggested.
 ...
PMID:Asbestos fibers induce release of collagenase by human polymorphonuclear leukocytes. 217 48

Analysis of the transforming growth factor alpha (TGF alpha) cDNA predicts that the mature TGF alpha polypeptide is cleaved from the extracellular domain of its precursor, which is an integral membrane protein. Furthermore, the cleavage sites for the release of this mitogen are compatible with the participation of an elastaselike protease. We have immunohistochemically localized TGF alpha to the vascular smooth muscle cells in the arterioles. To investigate whether polymorphonuclear (PMN) leukocytic elastase, a blood-borne protease, could process the cell surface TGF alpha, NR6 cells were transfected with the rat TGF alpha cDNA. The cDNA encoded the entire open reading frame, and its expression was under the control of the mouse metallothionein I promoter. A cloned transfectant, termed 1B2, synthesized the TGF alpha precursor in a zinc-inducible manner, and the precursor was localized to the cell surface. Western blot (immunoblot) analysis indicated that treatment of the zinc-induced 1B2 cells with either PMN leukocytic or pancreatic elastase resulted in the release of the mature TGF alpha polypeptide. The released TGF alpha was bioactive, as it was capable of both competing with epidermal growth factor for binding to its receptor and stimulating [3H]thymidine incorporation in the mitogenic assay. Formaldehyde fixation of the 1B2 cells eliminated basal release of TGF alpha but allowed normal processing by both PMN leukocytic and pancreatic elastase to occur. However, human cathepsin G, bovine pancreatic alpha 1-chymotrypsin, collagenase, trypsin, subtilisin, and plasmin failed to release any detectable fragments of the TGF alpha precursor from the fixed cells. The location of TGF alpha in the arterioles and ability of PMN leukocytic elastase to process the membrane-bound TGF alpha precursor suggests a novel role for this elastase at the wound site.
 ...
PMID:Transforming growth factor alpha in arterioles: cell surface processing of its precursor by elastases. 220 95

We have recently demonstrated that polymorphonuclear neutrophils were toxic to hepatocytes through a protease-mediated mechanism. Since synthesis of antiproteases is markedly increased during acute inflammatory reaction, the aim of this work was to investigate the toxicity of neutrophils against normal vs. inflammatory rat hepatocytes. Acute inflammatory reaction was induced by subcutaneous injection of turpentine 24 hr before the experiments. Hepatocytes from normal and turpentine-treated rats were isolated by collagenase digestion. They were incubated with human neutrophils stimulated by 1 mg/ml opsonized zymosan. Cytotoxicity was quantified by the percentage of alanine aminotransferase activity released by hepatocytes in culture medium after an 18-hr incubation period. By comparison to normal hepatocytes, inflammatory hepatocytes were more resistant to the toxicity of neutrophils. At a neutrophil/hepatocyte ratio of 20:1, the alanine aminotransferase activity releases were 53.7% +/- 5.4% (mean +/- 1 S.E.) and 27.4% +/- 4.8% for normal and inflammatory hepatocytes, respectively. Similarly, inflammatory hepatocytes were found to be less sensitive than normal hepatocytes to the toxic effect of purified neutrophil cathepsin G. In contrast, both types of hepatocytes exhibited the same sensitivity to H2O2 generated by a system consisting of glucose and glucose oxidase. Two arguments suggested that the resistance of inflammatory hepatocytes to protease toxicity was explained by an increased production of antiproteases by these cells: (a) when tested against cathepsin G and porcine pancreatic elastase activities, the protease inhibitory capacity of conditioned medium from inflammatory hepatocytes was higher than that of conditioned medium from normal hepatocytes; (b) conditioned medium from inflammatory hepatocytes markedly reduced the toxicity of stimulated neutrophils as that of cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Decreased toxicity of polymorphonuclear neutrophils toward hepatocytes isolated from rats with acute inflammatory reaction. 225 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>