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:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymorphonuclear leukocytes have been shown to contain proteolytic enzymes which are capable of degrading connective tissue proteins such as native collagen. In this study, proteolytic enzymes were extracted from human polymorphonuclear leukocytes and a neutral proteinase was extensively purified and characterized. The activity of this enzyme was monitored by degradation of denatured [ 3H ]proline-labeled type I collagen or by cleavage of a synthetic dinitrophenylated peptide with a Gly-Ile sequence. The enzyme was readily separated from leukocyte collagenase by concanavalin-A--Sepharose affinity chromatography and further purified by QAE-Sephadex ion-exchange chromatography and gel filtration on Sephacryl S-200. The purified enzyme had a molecular weight of approximately 105000, its pH optimum was about 7.8, and it was inhibited by Na2EDTA and dithiothreitol, but not by fetal calf serum. The enzyme degraded genetically distinct type I, II, III, IV and V collagens, when in a non-helical form, but not when in native triple-helical conformation. Dansyl-monitored end-group analyses, combined with digestion by carboxypeptidase A, indicated that the enzyme cleaved denaturated type I collagen at Gly-Xaa sequences, in which Xaa can be leucine, isoleucine, valine, phenylalanine, lysine, or methionine. Thus, the purified enzyme referred to here as Gly-Xaa proteinase, is a neutral proteinase, which may be of importance in inflammatory disease processes by degrading further collagen peptides which have been rendered non-helical as a result of collagenase cleavage.
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PMID:Proteinases in human polymorphonuclear leukocytes. Purification and characterization of an enzyme which cleaves denatured collagen and a synthetic peptide with a Gly-Ile sequence. 634 59

Human plasma fibronectin (FN) is not susceptible to collagenase and gelatinase from human blood leukocytes. Leukocytic elastolytic protease (ELP) and cathepsin G (chymotrypsin-like protease, CLP) degrade FN to similar fragments. Among products of proteolysis by ELP and CLP fragments have been identified which bind to gelatin-fragment 40 kd, to fibrin-fragments 55 kd and 30 kd, and to heparin-fragment 30 kd.
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PMID:Effects of neutral proteases from human leukocytes on plasma fibronectin. 637 56

Cells derived from isolated glomerular tufts of rats were studied in primary tissue culture after the removal of epithelial cells by collagenase treatment. The cultured cells, fusiform or stellate in shape, grew readily over a 12-day period. Immunofluorescence staining was positive for myosin and fibronectin, while negative for Factor VIII, suggesting that the outgrowing cells were derived from the glomerular mesangium. In serum-free culture, these cells produced neutral proteinase activity that occurred as a latent trypsin-activable form (apparent molecular weight range, 78,000 to 100,000 daltons) and in an active form (44,000 to 58,000 daltons). Neutral proteinase activity was inhibited by EDTA and by cysteine, and exhibited a pH optimum of 7.2 to 7.8, characteristic of an extracellularly active metalloendopeptidase. The culture supernate which contained the neutral proteinase activity was capable of degrading purified rat glomerular basement membrane. The release of hydroxyproline-containing fragments from the basement membrane indicated that degradation of the type IV collagen component of the basement membrane was occurring. These findings suggest that the neutral proteinase activity generated by mesangium-derived cells may play a role in the physiologic turnover of glomerular structural proteins in vivo.
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PMID:Neutral proteinase activity produced in vitro by cells of the glomerular mesangium. 640 73

The correlation between activation of macrophages and increased secretion of plasminogen activator suggests that macrophages are exposed to the protease plasmin. Incubation of 125I-labeled, caseinate-elicited guinea pig peritoneal macrophages with plasmin cleaves a surface protein, gp160, characterized previously by its sensitivity to trypsin. The gp160 fragments produced by plasmin (fr85 and fr71), which remain disulfide-bonded in the membrane, comigrate with the fragments produced by trypsin, indicating close or identical cleavage sites. No other detectable 125I-labeled surface component is cleaved by plasmin. Neither gp160 nor any other detectable 125I-labeled surface component was cleaved by a series of other proteases associated with inflammation including thrombin, collagenase, pancreatic elastase, leukocyte elastase, cathepsin G, and urokinase. Analysis with the use of homogeneous plasmin from guinea pig plasma shows that concentrations as low as 50 micrograms/ml cause measurable cleavage of gp160 in 30 min.
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PMID:Macrophage surface component gp160: sensitivity to plasmin and other proteases. 646 Aug 5

When cultured together with dead 35S-labelled cartilage discs or at the surface of [3H]proteoglycan/[14C]collagen-coated plates, synovial cells from either arthritic or normal rabbit joints digested both the proteoglycan and the collagen of the substrates after a lag-period of 1-2 days. These digestions were inversely related to the age (number of subculture passages) of the synovial cells and they could be modulated by serum components that were either inhibitory or stimulatory. They were dependent on a protein synthesis by the cells and were paralleled, in young cultures, by the release of collagenase and of a proteoglycan-degrading neutral proteinase. The co-culture of synovial cells with macrophages or their culture with macrophage-conditioned culture media caused a more rapid and more extensive degradation of collagen and proteoglycan due to the stimulation of the synovial cells by a nondialysable macrophage factor. The production of this synovial cell-activating 'matrix regulatory monokine' by the macrophage was enhanced by several immunological or inflammatory stimuli such as lymphocyte factors, phagocytosis, asbestos fibres, endotoxin, adjuvant muramyl dipeptide or chemotactic formyl-methionyl peptide, as well as by other membrane-active agents (phorbol myristate acetate, concanavalin A). It is presumed that these interactions are of importance in the development of cartilage destruction in rheumatoid and other chronic inflammatory arthritis.
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PMID:Degradation of cartilage proteoglycan and collagen by synovial cells. Stimulation by macrophages under activation by phagocytosis, lymphocyte factors, bacterial products or other inflammatory stimuli. 646 14

1. A radiochemical plate assay is presented that allows a simultaneous evaluation of the capacity of cells in culture to degrade proteoglycan and collagen. Its principle consists of monitoring the release of soluble radioactive degradation products from Multiwell culture plates coated with dried reconstituted 3H-labelled-proteoglycan/14C-labelled-collagen mixed gels. The plates can also be used for the assay of proteolytic activities within enzyme solutions. 2. When cultured on the plates, rabbit synovial cells degrade collagen and proteoglycan almost simultaneously, owing to the secretion of collagenase and of a proteoglycan-degrading metal-dependent neutral proteinase.
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PMID:A direct simultaneous plate assay of proteoglycan and collagen degradation by cells in culture and its application to synovial cells. 730 82

The degradation of tenascin purified from human melanoma cells was examined by treatment with matrix metalloproteinases (MMPs) and serine proteinases. Among eight different types of proteinases examined, MMP-1, -3, and -7, cathepsin G and leukocyte elastase could digest tenascin, but MMP-2, MMP-9 and thrombin did not. This suggests that tenascin may be readily catabolized by extracellular matrix-degrading proteinases found in the pathophysiological conditions.
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PMID:Susceptibility of tenascin to degradation by matrix metalloproteinases and serine proteinases. 752 86

Dental plaque is the major aetiological factor in periodontal diseases and contains several proteolytic enzymes. The origin of these proteinases is, however, poorly studied. This study was undertaken to characterize collagenase present in dental plaque of adult periodontitis patients. Vertebrate-type rather than bacterial-derived collagenase activity was detected in extracts of both supra- and subgingival dental plaque extracts of adult periodontitis patients. Dental plaque collagenase was found to exist predominantly in autoactive form. Dental plaque collagenase from periodontally healthy individuals existed in latent from. Latent dental plaque collagenase from periodontitis lesions could be activated by a 95 kD chymotrypsin-like proteinase from Treponema denticola and human leukocyte cathepsin G but not by human plasmin. Incubation of purified latent leukocyte collagenase with whole cells of Fusobacterium nucleatum, Eubacterium saburreum, Prevotella buccae and Porphyromonas gingivalis, however, did not result to the activation of the enzyme. Doxycycline in vitro inhibited dental plaque collagenase with an IC50-value of 20 microM. Dental plaque collagenase degraded more efficiently type I and II collagens than type III collagen. Western-blot analysis with specific anti-human neutrophil collagenase-antibody revealed that both in supra- and subgingival dental plaque extracts dental plaque collagenase had undergone proteolytic conversion from an 80 kD proform to a 58 kD active form which is associated with catalytic autoactivity as measured by functional collagenase assay. This reflects proteolytic activation of leukocyte collagenase in dental plaque probably by other proteases derived from potent periodontopathogenic bacteria such as T. denticola or other PMN proteases such as cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular source, activation and inhibition of dental plaque collagenase. 759 2

The volatile sulphur compound methyl mercaptan (CH3SH) is a by-product of protein metabolism and a principal component of oral malodour. This investigation examines the effect of CH3SH on the enzymatic activities of cathepsins B and G and elastase, and on the production by human gingival fibroblasts of two key factors, prostaglandin E (PGE) and cAMP, of the PGE2-cAMP-dependent pathway, which may contribute to the increased production of collagenase and tissue destruction in human periodontal disease. The results demonstrate that CH3SH alone, or in combination with interleukin-1 (IL-1) or lipopolysaccharide, can significantly enhance the secretion of PGE2, cAMP and procollagenase by human gingival fibroblasts. CH3SH also stimulated mononuclear cells to produce IL-1, which can increase cAMP production, and act in synergism with the direct effect of CH3SH on cAMP. CH3SH also significantly enhanced the activity of cathepsin B, moderately suppressed that of cathepsin G, but did not significantly affect elastase. These results provide evidence that CH3SH could be a contributing factor in the enzymatic and immunological cascade of events leading to tissue degradation in periodontal diseases.
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PMID:Stimulation of enzyme and cytokine production by methyl mercaptan in human gingival fibroblast and monocyte cell cultures. 760 61

Several members of the matrix metalloproteinase family have been reported to cleave aggrecan in the interglobular domain between Asn-341 and Phe-342. An antiserum was prepared against a peptide conjugate corresponding to the C-terminal sequence of the matrix metalloproteinase-generated aggrecan G1 fragment (Phe335-Val-Asp-Ile-Pro-Glu-Asn341). A quantitative radioimmunoassay, with a limit of detection of about 80 pM, was developed using this antiserum. This antiserum requires the free carboxyl group of the C-terminal asparagine for optimal recognition. If the C-terminal asparagine is excised from the sequence, replaced with closely related amino acids, or extended across the matrix metalloproteinase cleavage site, there is a 40-10,000-fold loss in detection. Using peptides cleaved from the N-terminus, it was determined that the antiserum requires the entire Phe-Val-Asp-Ile-Pro-Glu-Asn sequence for optimal recognition. The radioimmunoassay detects matrix metalloproteinase-generated G1 fragments with similar sensitivity to the Phe-Val-Asp-Ile-Pro-Glu-Asn peptide, but it does not recognize intact aggrecan. Immunoreactive aggrecan G1 fragments of molecular mass 50 kDa are generated by the matrix metalloproteinases stromelysin and gelatinase A. In contrast, under identical conditions, the closely related metalloproteinases, gelatinase B and collagenase, as well as cathepsin G, cathepsin B and human leucocyte elastase, did not generate a G1 fragment recognized by the antiserum. The anti-Phe-Val-Asp-Ile-Pro-Glu-Asn serum detects stromelysin-generated aggrecan G1 fragments from mouse, guinea pig, rabbit and human, indicating that the detection is not species-specific. This antiserum and radio-immunoassay should be useful for quantifying and characterizing matrix metalloproteinase-generated aggrecan G1 fragments in articular cartilage and synovial fluids from humans and various animal models of articular-cartilage destruction.
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PMID:Quantification of a matrix metalloproteinase-generated aggrecan G1 fragment using monospecific anti-peptide serum. 771 83


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