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)

In a series of experiments, Golub et al. demonstrated that tetracyclines, but not other antibiotics, can inhibit mammalian collagenases and proposed that this property could be useful in treating diseases, such as periodontal disease (but also included certain medical conditions, e.g., corneal ulcers) characterized by excessive collagen degradation (J Periodont Res 1983, 1984 and 1985; Experientia 1984; Cornea 1984). One effect was the dramatic reduction of tissue collagenase activity within the gingival crevicular fluid (GCF) of periodontal pockets after administering a standard regimen of a tetracycline (e.g., 200 mg minocycline or 1000 mg tetracycline/day). The preliminary studies described below determined the effect of (1) low-dose (LD; 40-80 mg/day) orally administered minocycline on GCF collagenase activity and on the subgingival microflora (Exp. I), and (2) tetracycline-loaded monolithic fibers (TF) on collagenase activity in vitro (Exp. II). In Exp. I, GCF collagenase activity was reduced by 45 to 80% 2 weeks after initiating LD minocycline therapy, an effect that lasted for at least several weeks after stopping drug treatment. No consistent change in the relative proportions of G(+), G(-) and motile subgingival microorganisms was detected as a result of LD treatment suggesting that the reduction in GCF collagenase activity was a direct inhibition of the enzyme by the drug. In Exp. II, 3- and 6-mm lengths of TF in vitro established tetracycline concentrations in 250 microliters of 132 micrograms/ml, from 3-mm lengths, and 265 micrograms/ml, from 6-mm lengths, after an 18-hour incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tetracyclines inhibit tissue collagenases. Effects of ingested low-dose and local delivery systems. 300 Dec 66

Human skin fibroblasts secrete collagenase as two proenzyme forms (57 and 52 kDa). The minor (57-kDa) proenzyme form is the result of a partial posttranslational modification of the major (52-kDa) proenzyme through the addition of N-linked complex oligosaccharides. Human endothelial cells as well as fibroblasts from human colon, cornea, gingiva, and lung also secrete collagenase in two forms indistinguishable from those of the skin fibroblast enzyme. In vitro tissue culture studies have shown that the level of constitutive synthesis of this fibroblast-type interstitial collagenase is tissue specific, varies widely, and correlates with the steady-state level of a single collagenase-specific mRNA of 2.5 kilobases. The tumor promoter, phorbol 12-myristate 13-acetate, apparently blocks the control of collagenase synthesis resulting in a similarly high level of collagenase expression (approximately equal to 3-7 micrograms of collagenase per 10(6) cells per 24 hr) in all examined cells. The constitutive level of synthesis of a 28-kDa collagenase inhibitor does not correlate with that of the enzyme. Phorbol 12-myristate 13-acetate stimulates the production of this inhibitor that in turn modulates the activity of collagenase in the conditioned media. As a result, the apparent activity of the enzyme present in the medium does not accurately reflect the rate of its synthesis and secretion.
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PMID:Human fibroblast collagenase: glycosylation and tissue-specific levels of enzyme synthesis. 301 33

The extreme morbidity that a severe chemical burn produces makes it imperative that immediate treatment be instituted for the purpose of restoration of the integrity and transparency of the cornea. The evolution of cicatrisation in severe chemical injuries especially alkali, takes an unfavourable course. Release of collagenase from the newly formed epithelium and fibroblasts of the stroma and lack of required levels of ascorbate in the aqueous humour causes fibroblasts to develop a denatured weak collagen.
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PMID:Management of chemical injuries of the eye. 350 19

A new connective tissue protein, which we call fibrillin, has been isolated from the medium of human fibroblast cell cultures. Electrophoresis of the disulfide bond-reduced protein gave a single band with an estimated molecular mass of 350,000 D. This 350-kD protein appeared to possess intrachain disulfide bonds. It could be stained with periodic acid-Schiff reagent, and after metabolic labeling, it contained [3H]glucosamine. It could not be labeled with [35S]sulfate. It was resistant to digestion by bacterial collagenase. Using mAbs specific for fibrillin, we demonstrated its widespread distribution in the connective tissue matrices of skin, lung, kidney, vasculature, cartilage, tendon, muscle, cornea, and ciliary zonule. Electron microscopic immunolocalization with colloidal gold conjugates specified its location to a class of extracellular structural elements described as microfibrils. These microfibrils possessed a characteristic appearance and averaged 10 nm in diameter. Microfibrils around the amorphous cores of the elastic fiber system as well as bundles of microfibrils without elastin cores were labeled equally well with antibody. Immunolocalization suggested that fibrillin is arrayed periodically along the individual microfibril and that individual microfibrils may be aligned within bundles. The periodicity of the epitope appeared to match the interstitial collagen band periodicity. In contrast, type VI collagen, which has been proposed as a possible microfibrillar component, was immunolocalized with a specific mAb to small diameter microfilaments that interweave among the large, banded collagen fibers; it was not associated with the system of microfibrils identified by the presence of fibrillin.
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PMID:Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. 353 67

Using nondegradative isolation procedures, we have purified and characterized the Mr 24,000 phosphoprotein from developing bovine and human bone where it constitutes 5% of the noncollagenous protein in the mineral compartment. This hydroxyproline-containing protein could not be cleaved by cyanogen bromide. The purified, intact product spontaneously formed a complex consistent with a collagen-like trimer that remained a trimer even in sodium dodecyl sulfate-polyacrylamide gels. The ability to form the complex was lost upon treatment with bacterial collagenase, a treatment that resulted in an NH2-terminally blocked fragment of Mr 17,000. After deblocking, the NH2-terminus of the intact, Mr 24,000 bovine product was shown to have virtually the same amino acid sequence (residues 1-24 with asparagine rather than aspartic acid at position 20 as reported earlier by Horlein et al. (Horlein, D., Fietzek, P. P., Wachter, E., Lapiere, C. M., and Kuhn, K. (1979) Eur. J. Biochem. 90, 31-38) as the amino-terminal segment of dermatosparatic calf skin alpha 1 type I procollagen. Furthermore, pulse-chase studies showed a precursor-product relationship between procollagen and the Mr 24,000 protein. Anti-serum made against the bovine bone protein bound to bands on electrotransfers that were consistent with the positions of both alpha 1(I) procollagen and the procollagen chain missing its COOH-terminal extension peptide (pN-alpha 1(I), as well as the original Mr 24,000 product in extracts of bone, skin, tendon, cornea, and other type I collagen-containing tissues. Fetal calf serum contained an average of 106 micrograms/ml of the Mr 24,000 protein as determined by quantitative enzyme-linked immunosorbent assay. The only serine residue in the bovine bone protein was phosphorylated. It is unknown whether the corresponding collagen NH2-terminal pro-peptides in other tissues and serum are similarly phosphorylated.
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PMID:The Mr 24,000 phosphoprotein from developing bone is the NH2-terminal propeptide of the alpha 1 chain of type I collagen. 365 22

Although xerophthalmia due to severe vitamin A deficiency is the leading cause of childhood blindness in the underdeveloped countries, little is known about the proteases (other than collagenase) that are involved in the degradative mechanism. The degree of cellular autolysis and stromal degradation observed histologically in early stages of xerophthalmia and in ulcerating corneas in vitamin A deficient rabbits in this study were, in general, proportional to the levels of the proteases studied. The only major histologic and ultrastructural alteration observed in early xerophthalmic corneas was autolysis of superficial epithelial and stromal cells. In contrast, in the ulcerating corneas the stroma was infiltrated heavily with inflammatory cells and extensive stromal degradation was observed in the central necrotic region of the lesions. Maximal proteolytic activity toward hemoglobin was observed at pH 3.3 for corneal extracts from normal (N) and pair-fed control (C) rabbits and rabbits with early xerophthalmia (X) and ulcerating xerophthalmia (U) corneas. This activity was a cathepsin D-like enzyme per cornea that had a ratio of 1:1:3:16 in the N, C, X, and U corneas. The ratio of cathepsin B-like activity per cornea for N, C, X, and U corneas was 1:2:2:10.
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PMID:Acid proteases and histologic correlations in experimental ulceration in vitamin A deficient rabbit corneas. 388 66

The early phase of wound healing after small central alkali burns of the guinea pig cornea was studied using electron microscopical, enzyme histochemical, and biochemical techniques. In the first phase, which was morphologically characterized by the destruction of the epithelium and keratocytes and by the infiltration of the cornea with polymorphonuclear leukocytes, an increase in the activity of lysosomal phosphatases and glycosidases (beta-D-glucuronidase, acid beta-D-galactosidase, beta-D-N-acetylglucosaminidase) was noticed. In the second phase, the cornea was invaded by capillaries and fibroblasts. In this phase, the activity of proteases (aminopeptidase M, dipeptidyl peptidase IV) increased intra- and extracellularly, suggesting that these enzymes may be involved in the turnover of the collagenous matrix and the ground substance. Using synthetic 4-methoxy-2-naphthylamine substrates and fluorescence-band detection techniques after isoelectric focusing, an increase in the activity of endopeptidases was demonstrated. The decreased activity of gamma-glutamyl transpeptidase may be linked with the activation of latent collagenase.
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PMID:The alkali burned cornea: electron microscopical, enzyme histochemical, and biochemical observations. 406 94

"Beaded filaments" have been found in fibroblast cultures prepared from chicken embryo leg tendons and cornea and from the dermis of human skin. With negative staining, they appear as single, unbranched, flexible strands approximately 3 nm in width and up to at least 2 microns in length. Pairs of "beads" are distributed on the filament at regular intervals of 110 nm. The beaded filaments appear to be resistant to the action of trypsin and bacterial collagenase. The filaments also occur in bundles with beads laterally aligned to form long-spacing-type fibrils, which appear to be identical with many fibrous-long-spacing-type fibrils described, but not identified, by others in a variety of normal and pathological tissues. The long-spacing fibrils are numerous at several sites of active collagen fibrillogenesis. Comparison of the beaded filament structure with molecular models for various collagens described in the literature suggests that they are a filamentous form of type VI collagen.
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PMID:Beaded filaments and long-spacing fibrils: relation to type VI collagen. 610 May 55

Cornea cells were isolated from bovine corneae after collagenase treatment. Subcellular fragments were fractionated by density gradient centrifugation. The density gradient run was monitored by determination of the marker enzyme activities for mitochondria, plasma membranes, lysosomes and endoplasmatic reticulum, of the enzyme activities involved in keratan sulfate synthesis and of the protein content. The fractions were further investigated by electron microscopy. Two membrane fractions with keratan sulfate-synthesizing activity (UDP-N-acetylglucosamine:keratan-N-acetylglucosaminyl-transferase, UDPgalactose:keratan galactosyltransferase and keratan sulfotransferase) were detected: a heavy fraction separated from the other organells investigated and a light fraction exhibiting the same density as plasma membranes. The activities of the three enzymes were found in the same density gradient fractions with a similar distribution pattern between the fractions, which suggests a joint localization of these 3 enzymes at the same intracellular sites.
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PMID:Biosynthesis of proteokeratan sulfate in the bovine cornea. 2) Isolation of subcellular membrane fragments from bovine cornea cells with keratan sulfate synthesizing activity. 622 57

Collagenase has been localized in human corneas using immunocytochemical techniques employing a specific antiserum to human skin collagenase. The enzyme was found in vivo in ulcerating corneas, whereas in corneas obtained from a variety of nonulcerative conditions, no immunologic evidence of the enzyme was seen. Corneal collagenase was present only in the stromal portion of the cornea, suggesting that cells from this tissue are the source of the enzyme. The localization of collagenase to the corneal stroma was reproduced by placing either ulcerating or nonulcerating corneas in tissue culture, indicating that the organ culture system may represent a model that duplicates some conditions present in corneal disease.
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PMID:Collagenase in human cornea: immunologic localization. 624 61


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