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)

Activated macrophages (M phi s) have terminal alpha-D-galactosyl (alpha D-Gal) residues on their membranes that are not apparent on resting cells. Ligation of these epitopes with Griffonia simplicifolia I-B4 (GSI-B4), a lectin that has specificity for alpha-D-Gal residues, alters selected M phi functions. To explore the mechanism(s) that may be responsible for some of the functional changes, alterations in the secretory pattern of [35S]methionine-labeled proteins were assessed when cells were cultured with or without this ligand. The proteins were identified by Western blots and quantitated. Interestingly, alpha-D-Gal ligation proved to decrease the secretion of some proteins while increasing the secretion of others. Some of the most significant changes were observed in four proteins: fibronectin and transglutaminase were down-regulated by 55 and 66% respectively, while plasminogen activator inhibitor type 2 was increased by 259% and collagenase was increased 1000-fold. These observations show that the emergence of new oligosaccharide epitopes, such as alpha-D-Gal, concomitant with M phi activation may serve to mediate the transduction of signals that cause quantitative changes in the elaboration of diverse M phi products. The biologic significance of the four identified proteins has been well established. Fluctuations in their levels are likely to play a role at sites of chronic inflammation.
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PMID:Specific ligation of surface alpha-D-galactosyl epitopes markedly affects the quantity of four major proteins secreted by macrophages. 137 96

The ability of various peptides cleaved by plasmin from human fibrinogen and fibronectin or fibrinogen- and fibronectin- related synthetic peptides to induce histamine release from mast cells and collagenase and elastase from PMN-leukocytes was examined. Low molecular weight fibrinogen degradation products showed dose dependent secretion of collagenase. These peptides (mol. wt. 1.4 kD) at the concentration of 10(-5) M released about 47% of collagenase and 13% of elastase. Synthetic fibrinopeptides A and B had a similar strong collagenase releasing potency and also released histamine from mast cells. Peptides from plasmin digestion of fibronectin containing cell attachment site with sequence Arg-Gly-Asp-Ser and also synthetic peptide reproducing this amino-acid sequence at the concentration of 1000 micrograms/ml released about 50% of collagenase and 55% of elastase from PMN-leukocytes. Moreover peptides containing cell attachment and gelatin binding site induced histamine release from mast cells. The association of fibrinogen and fibronectin degradation with activation of mast cells may motivate the treatment with antihistaminic drugs of all pathological conditions where the intensive protein degradation takes place.
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PMID:Fibronectin and fibrinogen degradation products stimulate PMN-leukocyte and mast cell degranulation. 138 26

Human vascular smooth muscle cells have been used to assess the implied role of connective tissue microfibrils as cellular ligands. Preparations of intact high-M(r) microfibrillar assemblies of collagen VI and of fibrillin, respectively, were isolated from foetal bovine skin and used as ligands in cell attachment and spreading assays. Intact collagen VI microfibrils were capable of mediating cell attachment and partial spreading. Cell attachment assays using ligands composed of defined collagen VI fragments generated by pepsin or bacterial collagenase digestions demonstrated that both the triple-helical and non-collagenous domains of collagen VI had cell adhesion activity, although at reduced levels relative to intact microfibrils. Fibronectin was identified as a modulator of intact collagen VI microfibril-mediated cell attachment. These observations are indicative of complex multiple interactions between collagen VI microfibrils and smooth muscle cells. Purified fibrillin-containing microfibrils were also shown to support smooth muscle cell adhesion. Both pepsin-resistant and pepsin-sensitive domains of fibrillin exhibited some cell attachment activity, but at reduced levels relative to the intact fibrillin microfibrils. These data provide the first direct evidence of a physiological role for intact microfibrillar assemblies in cell-matrix interactions, and the involvement of integrin cell surface receptors containing the beta 1 subunit.
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PMID:Attachment of human vascular smooth muscles cells to intact microfibrillar assemblies of collagen VI and fibrillin. 147 46

Bacterial collagenase from aerobic non-pathogenic Vibrio alginolyticus chemovar iophagus ("Achromobacter" collagenase, EC 3.4.24.08) is an inducible extracellular metallo-proteinase. Production of Vibrio collagenase is induced specifically by collagen or by its macromolecular fragments. On the cell surface is expressed a specific receptor recognizing collagen structure. The study of natural inducers led to synthetic peptides with inducing properties. Vibrio collagenase cleaves collagen helical chains preferentially at 3/4 from the N-terminal. Its specific activity on synthetic substrate, 180,000 ukat/mg, represents the highest value for known collagenases. Its specificity differs from that of Clostridium: The enzyme cleaves preferentially sequences with Gly or Ala in position P'1 and Pro in position P2 or P'2. Highly specific cleavages were obtained in beta-casein, prolactin, myosin, adenylate kinase and fibronectin. Autolysis yields partially degraded forms still active on native collagen and peptide substrate. The determination of the sequence of Vibrio collagenase is nearly achieved; the enzyme was not yet obtained in crystalline form. On basis of the already known sequence and structure of Hypoderma collagenase (EC 3.4.21.49), a hypothesis is advanced on the character of collagen binding site loops. Vibrio collagenase can be produced in kilogram quantities at low cost. It was found highly efficient in debridement of necrotic burns, ulcers and decubitus.
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PMID:Vibrio alginolyticus ("Achromobacter") collagenase: biosynthesis, function and application. 148 12

Inflammation of the periodontium leads to connective tissue degradation and eventual tooth loss. The regulation of matrix metalloproteinases (MMPs) has been studied to determine their role in these processes and also during tissue remodelling. Analysis of gingival crevicular fluid has revealed the presence of collagenase and gelatinase that, in the acute stages of periodontal disease, are derived predominantly from polymorphonuclear leukocytes. These MMPs appear to be intimately associated with tissue destruction since the levels of the active forms of these enzymes obtained from either crevicular fluid or mouthrinse samples correlate with tissue destruction and, therefore, provide a sensitive means of demonstrating disease activity. Transforming growth factor-beta, an important regulator of connective tissue remodelling, has been implicated in the rapid remodelling of periodontal tissues. TGF-beta promotes tissue matrix formation by stimulating both the synthesis of matrix proteins (collagen, fibronectin and SPARC) and proteinase inhibitors (TIMP, PAI-1) and by decreasing the synthesis of MMPs, but not the 72 kDa-gelatinase. Nuclear run-on analyses have shown that TGF-beta reduces collagenase and stromelysin synthesis by suppressing gene transcription without altering mRNA stabilities. In contrast, the transcription of the gelatinase and TIMP genes was increased by TGF-beta, which also increased gelatinase mRNA stability. Remodelling of alveolar bone involves interaction between osteoblasts and osteoclasts. Osteoblasts, under the influence of osteotropic hormones (vit D3, PTH and retinoic acid), produce MMPs which appear to function in the removal of soft tissue that precludes access of osteoclasts to the mineralized tissue surface. Rat osteoblastic cells produce MMPs with activity on native collagen, native collagen 3/4-fragments and gelatin and, in addition, two forms of TIMP activity. The 3/4-collagen endopeptidase, purified to apparent homogeneity, also has significant collagenase and gelatinase activities and an amino terminal sequence almost identical to human 72 kDa-gelatinase. The production of this enzyme was stimulated by TGF-beta, which suppresses bone resorption, and by osteotropic hormones which stimulate bone resorption, supporting a bifunctional role for the gelatinase in connective tissue remodelling. Although there is strong evidence for the involvement of MMPs in the resorption of bone and in the inflammation-mediated destruction of periodontal tissues, the role of MMPs in the remodelling of mature soft connective tissues remains equivocal.
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PMID:Matrix metalloproteinases in periodontal tissue remodelling. 148 60

Stromelysin/Transin is a member of the matrix metalloprotease gene family. This metalloprotease is synthesized as a preproenzyme with a predicted size of 53,977 Da including a 17 amino acid signal peptide. Prostromelysin is secreted from normal and transformed cells in two forms with apparent molecular masses on NaDodSO4 gels of 60 and 58-kDa. The minor 60-kDa species contains N-linked oligosaccharide(s). Stromelysin consists of three domains the amino terminal propeptide(s) domain contains the tribasic amino acid sequence RRK which is important in the proteolytic activation of this zymogen by trypsin-like serine proteases. The second domain consists of the catalytic domain which contains the zinc binding site. The carboxyl-terminal hemopexin domain has no known function and can be removed without a loss of enzymatic activity. Stromelysin has a broad range of substrate specificity including proteoglycans, casein, fibronectin, laminin, native type IV and IX collagen and gelatin but not type I collagen. In the presence of trypsin or plasmin, catalytic amounts of this enzyme can also fully activate interstitial fibroblast collagenase. We have developed a panel of monoclonal antibodies against stromelysin which will be useful for the tissue localization of the various species of this enzyme in tissues. In addition, we have demonstrated that either human rIL-1 (alpha) or rTNF (alpha) can stimulate the expression of this enzyme in cultured bovine articular cartilage at least 10-fold. Based on western blot analysis, the zymogen form of the enzyme was the major enzyme species detected in either the media or cartilage matrix compartments of cytokine treated cultures.
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PMID:Primary structure and function of stromelysin/transin in cartilage matrix turnover. 148 63

Gel electrophoretic analysis of the avian tectorial membrane under non-reducing conditions reveals the presence of 2 major proteins with apparent molecular masses of 195 and 41 kDa on 8.25% gels. Under reducing conditions, 6 polypeptides with apparent molecular masses of 146, 60, 56, 43, 35 and 31 kDa are consistently observed. None of these six polypeptides observed under reducing conditions are sensitive to digestion with collagenase, and all, except for the 43 kDa component, are degraded by treatment with cold acidic pepsin. The 60, 56 and 43 kDa polypeptides bind the peroxidase conjugated lectins from Canavalia ensiformis and Triticum vulgaris, indicating the presence of mannose, N-acetyl glucosamine and/or sialic acid. The 146, 60 and 56 kDa bands undergo a shift in electrophoretic mobility after treatment of native tectorial membranes with the enzyme neuroaminidase. Fibronectin and Type II collagen cannot be detected in the avian tectorial membrane by either immunoblotting or immunofluorescence techniques. Polyclonal antisera raised against the different polypeptides after partial purification by one dimensional gel electrophoresis confirm that these proteins are all components of the tectorial membrane, and show that they are restricted to the otolithic and tectorial membranes within the inner ear. Analysis of a wide variety of other tissue types indicates that the 60, 43 and 35 kDa components can only be detected within the inner ear, and that the antisera recognising the 146 and 31 kDa components only show cross-reactivity within the head, with the anti-146 kDa antibodies staining the mucus ducts supplying the olfactory epithelium and the anti-31 kDa antibodies staining granular elements in the cells of the respiratory epithelium. The results suggest that certain of the tectorial membrane components may be novel matrix molecules unique to the inner ear, and that some of the other proteins may be antigenically related to mucins.
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PMID:The protein composition of the avian tectorial membrane. 149 Aug 98

The aim of this study is to optimize conditions for growing endothelial cells on vascular biomaterials. Bovine cornea endothelial cells (BCEC), stimulated by basic Fibroblast Growth Factor (bFGF) secrete an extracellular matrix (ECM) similar to the Descemet membrane produced in vivo by these cells. This ECM, obtained by removing BCEC with an hypotonic shock can be used as a substratum for other endothelial cell growth. Human endothelial cells (HEC) were purified from omentum that was digested with a solution of collagenase-dispase, then filtered through nylon meshes. The cells were further purified by centrifugation onto a Percoll gradient. A comparative study on the attachment and growth of HEC on various coatings (laminin, poly-L-lysine, fibronectin or ECM) indicates that ECM is the most performing substratum. The quality of this endothelium was confirmed by the presence of factor VIII, and MHC class I and the absence of class II antigens.
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PMID:Extracellular matrix covered biomaterials for human endothelial cell growth. 149 48

Whereas mesangial and epithelial cells from glomeruli are commonly grown in vitro, there has been a failure to isolate and propagate human glomerular capillary endothelial cells. This study defines the conditions for the reproducible isolation and growth of homogeneous monolayers of primate (baboon and human) glomerular capillary endothelial cells. Using selective media and growth factors, the following criteria were identified to optimize the isolation and proliferation of glomerular endothelial cells: (1) collagenase treatment of isolated glomeruli; (2) requirement for 20% serum, endothelial cell growth factor and heparin; (3) requirement of fibronectin as surface matrix; and (4) isolation from donors less than 60 years old, as premature senescence was directly proportional to the age of the human kidney donor. Under these conditions, primary cultures with an endothelial cell composition greater than 70% were reproducibly obtained. Homogeneous endothelial monolayers were developed from 20 of 23 human kidneys, and maintained for 5 to 10 passages, depending on the age of the kidney donor. Purification to homogeneity was achieved by patch cloning or by fluorescence-activated cell sorting. Glomerular capillary endothelial cells exhibited a cobblestone morphology at confluence, expressed factor VIII-related antigen, angiotensin converting enzyme activity, and endocytosed acetylated low-density lipoproteins. Electron microscopy revealed the presence of intracellular Weibel-Palade bodies and caveolae and microvillous projections on the luminal surface. Glomerular cells also stained positive for Ulex europaeus, a lectin characteristic of human endothelial cells. In addition, preliminary results indicate that human glomerular endothelial cells increase intracellular cyGMP in response to alpha-human 5 to 28 atrial natriuretic peptide and intracellular free calcium in response to thrombin.
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PMID:Culture of endothelial cells from baboon and human glomeruli. 150 7

The extracellular matrix (ECM) of articular cartilage is subject to a steady remodelling process. The collagenous components of the ECM are characterized by a very low rate of metabolism, whereas the proteoglycans exhibit an active turnover. The main proteolytic enzymes degrading the ECM components are collagenase, gelatinase and stromelysin. These enzymes undergo under pathological circumstances a remarkable enhancement of synthesis and activity. Although each of these enzymes appears to degrade one ECM component specifically, there is evidence for synergistic effects of most of them. Gelatinase acts synergistically with collagenase in degrading insoluble interstitial collagens and stromelysin activates collagenase. Thus a cascade mechanism may exist in which the cartilage-ECM is completely degraded. Yet, it is not crucial which part of the ECM (collagens or proteoglycans) is primarily degraded. The integrity of the ECM rather depends on the balance between anabolic and catabolic processes, the upset of which results in damage of the articular cartilage. Cartilage destruction in rheumatoid arthritis and osteoarthritis is considered to be a result of this imbalance in favour of the catabolic processes. This would lead to a decrease in proteoglycans which causes fibronectin deposition in the cartilage ECM. Due to chemotaxic effects of fibronectin on fibroblasts, the enrichment of this glycoprotein in the ECM gives rise to cartilage fibrosis and early degeneration.
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PMID:[Proteolytic enzymes and the destruction of articular cartilage in arthritis and chronic polyarthritis]. 164 88


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