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

---

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

The collagenase activity had been compared in extracts of eosinophils and of neutrophilss from peritoneal exudates in two groups of rats, one of which had been treated to augment the numbers of eosinophils and the other the numbers of neutrophils. The proportion of granulocytes to other cells in each preparation was increased by differential centrifugation over a continuous gradient. Collagenase was extracted from the fractions in which granulocytes were concentrated and the activity assayed by the radioactive fibril method. There was at least as much collagenase in the eosinophil-enriched extracts as in the neutrophil-enriched extracts. It is postulated that eosinophil collagenase may have a function in the remodelling of newly-synthesised collagen during the post-inflammatory phase of healing, since eosinophil leucocytes appear in significant numbers within the connective tissue during this phase. This suggests a different role for eosinophil collagenase than that for neutrophil collagenase, since neutrophil are present only in the early stages of inflammation, when collagen is being degraded.
...
PMID:Comparison of collagenase activity in eosinophil and neutrophil fractions from rat peritoneal exudates. 19 Sep 90

Using preparations of latent collagenase derived from neutrophil specific granule extracts, the relative effects of cathepsin G and HOCl on activation of neutrophil collagenase were determined using a quantitative collagenase assay. Enhancement of collagenase activity by cathepsin G and physiologically relevant concentrations of HOCl were comparable, but HOCl mediated collagenase activation was reversible in the presence of HOCl scavenger. Collagenase activity in preparations treated with cathepsin G and HOCL simultaneously or sequentially was significantly greater than activity in preparations treated with HOCl or cathepsin G alone. The results indicated additive, yet independent enhancing effects of HOCl and cathepsin G on activity of neutrophil collagenase.
...
PMID:Additive enhancement of neutrophil collagenase activity by HOCl and cathepsin G. 131 25

Accelerated periodontal tissue destruction in patients with labile insulin-dependent diabetes mellitus (DM) and localized juvenile periodontitis (LJP) has been suggested to be related to functional abnormalities of neutrophils. We have recently found that collagenase in gingival crevicular fluid (GCF) of adult periodontitis patients is primarily derived from neutrophils and that neutrophil collagenase activity is more sensitive to inhibition by tetracyclines than collagenase produced by fibroblasts. This study is to characterize the cellular sources, activation and inhibition of collagenase in GCF of DM patients and to compare it with collagenase in LJP GCF. We found differences which may have therapeutic implications. Specific doxycycline inhibition tests revealed that GCF collagenase in DM is derived from neutrophils, whereas the enzyme in LJP originates primarily from fibroblasts. Oxidant, sodium hypochlorite, activated efficiently GCF collagenase of DM but not LJP patients. In contrast, plasmin activated LJP GCF collagenase but not that of DM patients. In GCF of DM patients 50-60% of collagenase existed in an active form, whereas in LJP GCF, the enzyme was almost completely in a latent form. The results suggest that collagenase in GCF of periodontitis patients with labile DM is primarily derived from neutrophils and that tetracycline therapy may be an effective adjunct in treatment aimed at controlling the periodontal breakdown in these patients. On the other hand, in LJP the anti-collagenase property of tetracyclines may be less important for control of periodontal tissue destruction because of the tetracycline-resistance of fibroblast collagenase.
...
PMID:Cellular source and tetracycline-inhibition of gingival crevicular fluid collagenase of patients with labile diabetes mellitus. 131 30

Mammalian interstitial collagenases (E.C.3.4.24.7) are considered as key initiators of collagen degradation in periodontal diseases. However, the cellular sources of collagenases present in gingival crevicular fluid have not been completely clarified. Resident fibroblasts and epithelial cells as well as infiltrating neutrophils and monocyte/macrophages are potential sources of the enzymes. We have recently found significant differences in tetracycline inhibition between human neutrophil and fibroblast interstitial collagenases. To address the cellular source of collagenase present in gingival crevicular fluid in 2 distinct periodontal diseases, we studied the tetracycline inhibition of collagenase in gingival crevicular fluid of patients with localized juvenile periodontitis and adult periodontitis. Gingival crevicular fluid samples were collected from deep (greater than 5 mm) periodontal pockets and assayed for collagenase in the presence of 0-1000 microM doxycycline as well as a chemically modified tetracycline devoid of antimicrobial activity (4-de-dimethylaminotetracycline). The drug concentration required to inhibit 50% of collagenase activity (IC50) in localized juvenile periodontitis gingival crevicular fluid was 280 microM for doxycycline and 470 microM for 4-de-dimethylaminotetracycline. Significantly lower values, 10-20 microM, were obtained for collagenase in gingival crevicular fluid of patients with adult periodontitis. We propose that systemic tetracycline levels are efficient inhibitors of collagenase in gingival crevicular fluid in affected sites of patients with adult periodontitis but not of patients with localized juvenile periodontitis and that the fibroblast type interstitial collagenase is the predominant collagenase type in gingival crevicular fluid in affected sites of patients with localized juvenile periodontitis and the neutrophil collagenase in adult periodontitis gingival crevicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Tetracycline inhibition identifies the cellular origin of interstitial collagenases in human periodontal diseases in vivo. 132 40

Mouse collagenase cDNA was cloned and sequenced. The deduced amino acid sequence was compared to those of the other mammalian collagenases and related matrix metalloproteinases. These comparisons, as well as those of some enzymatic properties, show that the rodent (mouse and rat) interstitial collagenases are very similar but differ more from the other interstitial collagenases than does human neutrophil collagenase. This supports the hypothesis that the order Rodentia is an outgroup to the other eutherian (placental) mammalian orders.
...
PMID:Cloning and sequencing of mouse collagenase cDNA. Divergence of mouse and rat collagenases from the other mammalian collagenases. 138 28

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.
...
PMID:Collagenase in synovitis of rheumatoid arthritis. 141 81

Tetracyclines have recently been shown to inhibit the activity of mammalian matrix metalloproteinases, i.e. type I collagenase (MMP-1) and type IV collagenase/gelatinase (MMP-2). The specificity of this effect, however, has not been examined in detail. In the present study, doxycycline (a clinically widely used commercial tetracycline) and 4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial collagenases, which are distinct gene products, as well as collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic adult periodontitis patients. The concentrations of these two tetracyclines, required to inhibit 50% of the collagenase activity (IC50), were found to be 15-30 microM for purified human neutrophil collagenase as well as collagenase in gingival crevicular fluid of adult periodontitis patients and diabetic adult periodontitis patients, thus approximating in vivo therapeutic tetracycline levels. In contrast, the fibroblast collagenase and collagenase in gingival crevicular fluid of patients with juvenile periodontitis were relatively resistant to tetracycline inhibition: the IC50 for doxycycline and CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases. 142 10

Human neutrophil cathepsin G has been identified as a potent proteolytic activator of latent human neutrophil collagenase in vitro. In order to examine the role of cathepsin G in the activation mechanism of latent human neutrophil collagenase in vivo, gingival crevicular fluid was collected from periodontal pockets of patients with adult periodontitis and the relationship of cathepsin G to the proportion of endogenously active collagenase and total collagenase activity was determined. The changes in these parameters were monitored before and after periodontal therapy and compared to control values obtained for periodontal sites without clinical signs of inflammation or increased pocket depth. A significant decrease in cathepsin G and collagenase activity in gingival crevicular fluid collected from initially deep periodontal pockets was observed in response to scaling and root planing (P less than 0.025, Wilcoxon signed rank test). Also the proportion of endogenously active collagenase decreased (P less than 0.05). There was a significant correlation of cathepsin G and total collagenase activity. However, no correlation of cathepsin G activity and endogenously active collagenase was observed. The results indicate the existence of several distinct activation pathways for latent human neutrophil collagenase in vivo and suggest that, apart from cathepsin G, other proteolytic activation cascades and/or non-proteolytic activation pathways participate in the activation of latent human neutrophil collagenase in vivo.
...
PMID:Relationship of collagenase and cathepsin G activity in gingival crevicular fluid. 143 26

The effects of various reactive oxygen species on latent human neutrophil and fibroblast-type interstitial collagenases were studied. Latent human neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous acid and hydrogen peroxide and less efficiently by the serine proteinases trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate latent human neutrophil collagenase. The activation of latent human neutrophil collagenase by hypochlorous acid and hydrogen peroxide corresponded to the activation obtained with the other known non-proteolytic activators phenylmercuric chloride and gold thioglucose. The activation by hydrogen peroxide was inhibited by mannitol and desferoxamine, suggesting a localized Fenton-type reaction to be responsible for the generation of hydroxyl radical and/or hydroxyl radical-like reactive oxygen pathway of neutrophil procollagenase does not involve plasmin and plasma kallikrein, which are efficient proteolytic activators of latent fibroblast-type procollagenase (proMMP-1). Fibroblast procollagenase was also slightly activated by hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to prefer non-proteolytic means of activation and reactive oxygen species can be regarded as potent activators in vivo. Synovial-fluid neutrophils from rheumatoid arthritis patients were found to release collagenase in 30% active form when compared to same patients' peripheral blood neutrophils, which released collagenase in completely latent form. This may indicate that the triggering of neutrophil at the site of inflammation in vivo involves initial oxidative activation of collagenase upon the degranulation process.
...
PMID:Reactive oxygen species as regulators of human neutrophil and fibroblast interstitial collagenases. 144 75

Human neutrophil collagenase (HNC) has been purified from extracts of fresh and outdated buffy coats and from the exudates of phorbol myristate acetate-stimulated neutrophils. The HNC present in the starting material from such preparations can be either latent or active, or have an approximate molecular weight of 75 or 58 kDa, depending upon whether the extraction buffer contains protease inhibitors and/or antioxidants. The purification of these different forms of HNC is described and is made possible by taking appropriate precautions to stabilize the HNC. For example, a purification protocol is described that allows the purification to homogeneity of the active and PCMB-active latent 58 kDa forms of HNC in high yield with specific collagenase activities that greatly exceed that of trypsin-activated human fibroblast collagenase (HFC). The pattern of activation of the latent 58 and 75 kDa species by trypsin, organomercurials and oxidants has been investigated. HNC is shown to preferentially hydrolyze type I over types II and III collagens in solution. The specificity of HNC toward the hydrolysis of 60 octapeptides has been examined and compared with HFC. HNC is shown to be a glycoprotein that contains complex N-linked oligosaccharides.
...
PMID:Human neutrophil collagenase. 148 44


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

---