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)

Seven biopsy specimens from the cervix and 17 from the lower uterine segment were obtained in 24 women at term (37 to 42 weeks). Collagenase was extracted and assayed on telopeptide-free [3H]collagen; typical collagen cleavage products were found on sodium dodecyl sulfate-gel electrophoresis. There was no significant difference between collagenase levels in the cervix and in the lower uterine segment in women not in labor and with the cervix closed. Levels of active and latent collagenase in 11 such specimens were 0.14 +/- 0.03 and 0.64 +/- 0.90 U/gm wet weight, respectively (mean +/- SEM; 1 U = 1 micrograms collagen digested per minute at 30 degrees C). Thirteen women at term in active labor with cervical dilation of 4 to 8 cm exhibited a thirteenfold increase in mean collagenase activity in the lower uterine segment. Active and latent collagenase increased to 2.06 +/- 0.92 and 8.64 +/- 2.87 U/gm, respectively. This is the first direct evidence that interstitial collagenase increases markedly during cervical dilation in human parturition.
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PMID:Elevated tissue levels of collagenase during dilation of uterine cervix in human parturition. 284 86

Since its discovery, vertebrate collagenase is postulated to be the key enzyme for collagen degradation, but the evidence for its participation in bone resorption was, until recently, very weak. The osteoclast, which is the major bone resorbing cell, does apparently not produce collagenase but lysosomal acid proteinases, including collagenolytic cysteine proteinases, whose involvement in bone resorption is supported by many observations. Recent reports indicating 1) that osteoblasts produce and secrete collagenase in response to bone resorbing hormones and 2) that bone resorption is inhibited by a specific collagenase inhibitor, have reintroduced collagenase as a plausible participant in the mechanisms of bone resorption. Moreover bone resorbing agents do not act directly on osteoclasts, but on osteoblasts which, by an unknown mechanism, induce the osteoclasts to excavate bone matrix. Collagenase could participate in the control of bone resorption by degrading the unmineralized collagen which seems to shield the underlying bone from osteoclastic attack. In addition, collagenase, stored as a latent proenzyme in the mineralized matrix, might cooperate with the lysosomal cysteine proteinases in the subosteoclastic lysis of demineralized collagen.
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PMID:The role of collagenase in bone resorption. An overview. 285 68

An interstitial collagenase was purified from the explant medium of bovine dental pulp and was shown to degrade collagens I and III but not IV and V. The enzyme halted cleft initiation in the epithelium of 12-day mouse embryonic submandibular glands in vitro, indicating the active involvement of interstitial collagens in the branching morphogenesis. Transmission electron microscopic observation of the intact 12-day gland without any clefts showed the scattered localization of a few collagen fibrils at the epithelial-mesenchymal interface of the bulb and also revealed the presence of numerous microfibrils around the stalk. Collagen bundles were regularly seen close to the wavy basal lamina at the bottom of clefts of the intact 13-day gland and 12-day gland cultured for 17 h under normal conditions. Mesenchymal cells were found in the clefts together with the frequent localization of peripheral nerve fibres and capillary endothelial cells. The collagen bundles were more often observed in the 12-day gland cultured in the presence of bovine dental pulp collagenase inhibitor, which had been shown to enhance cleft formation. In contrast, collagen fibrils were rarely found at the epithelial-mesenchymal interface of the 12-day gland cultured in the presence of Clostridial or bovine dental pulp collagenase. The findings indicated that the formation of interstitial collagen bundles is essential to form clefts in the epithelium both in vivo and in vitro.
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PMID:The role of interstitial collagens in cleft formation of mouse embryonic submandibular gland during initial branching. 285 95

Evidence is presented that biopsy specimens from fibroadenomas, benign cystic lesions, and carcinomas of the human breast can produce in organ culture a neutral protease capable of digesting type I collagen. This enzyme activity, measured with the use of a radioactive release assay, was characterized as true vertebrate collagenase and occurred in both active and latent (requiring trypsin activation) forms. For the two types of benign breast lesion studied, collagenase secretion was significantly higher from fibroadenomas than from benign cystic tissue. Breast carcinomas, however, exhibited a wide quantitative spectrum of collagenase secretion, encompassing the extremes observed for the benign lesions and showing no correlation with histologic type. These results, while providing a plausible mechanism for the marked collagen degradation seen in disseminating neoplasms, demonstrate that high collagenase secretory activity is not pathognomonic of invasive behavior. The findings, however, indicate disordered regulation of collagenase activity in malignant tumors.
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PMID:Collagenase secretion by human breast neoplasms: a clinicopathologic investigation. 298 53

Collagenase from normal human skin fibroblasts was found to catalyze the hydrolysis of esters and thio esters. This observation led to the development of a rapid, sensitive, continuous spectrophotometric assay for vertebrate collagenase using the thio peptolide Ac-ProLeuGly-S-LeuLeuGly-OC2H5 as substrate in the presence of 4,4'-dithiodipyridine or Ellman's Reagent. A Km of 0.004 M and a kcat of 370,000 h-1 were determined for the thio peptolide-enzyme reaction. The method is able to detect collagenase at concentrations as low as 2 ng/ml.
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PMID:Spectrophotometric assay for vertebrate collagenase. 299 Feb 54

Although the fibrosis observed during chronic liver injury is the result of a complex process, the striking accumulation of collagen in end stage liver disease has provoked interest in the mechanisms that regulate both collagen production and degradation in the diseased liver. The present studies have examined the cell interactions that may be important in the regulation of collagen degradation. Although minimal amounts of interstitial collagenase activity were noted in cultures of normal hepatocytes and sinusoidal cells, the co-cultures of these cells in the presence of lipopolysaccharide showed a substantial increase in collagenase activity. When the hepatocytes were obtained from rats that had been treated with carbon tetrachloride in vivo, the enhanced activity seen in the co-cultures did not require the addition of lipopolysaccharide. Further characterization of this interaction suggested that the increase in collagenolytic activity was partially due to the elaboration of soluble factors by the hepatocyte, which stimulated collagenase production by the sinusoidal cell population. Elaboration of collagenase activity by the sinusoidal cells was inhibited by cycloheximide, suggesting that protein synthesis was required. The proteolytic activity was abrogated by inhibitors of metalloproteinases but not by serine or thiol proteinase inhibitors. The degradation products of type I collagen were typical of the expected products seen with vertebrate collagenases. Thus, it appears that the increased collagenolytic activity detected in this co-culture system is attributable to the production of interstitial collagenase by the sinusoidal cell population. Such cell-cell interactions may play an important role in the maintenance of normal connective tissue structure of the liver during disease processes.
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PMID:Stimulation of interstitial collagenase in co-cultures of rat hepatocytes and sinusoidal cells. 300 4

Type X collagen was cleaved at two sites by a purified human skin collagenase. Two experimental approaches were used to identify the location of the cleavage sites. First, native type X collagen was digested with the enzyme, and the rotary-shadowed products were visualized in the electron microscope. The major collagenase fragment of type X contained the epitope recognized by a monoclonal antibody (X-AC9). The antibody was used as a point of reference to locate the position of the cleavage fragment within the native molecule. Second, the digestion of radiolabeled type X collagen substrates was analyzed by gel electrophoresis. The complete cleavage of type X generated three products with 32-, 18-, and 9-kDa chains. The 32-kDa peptides were present in a triple-helical conformation and demonstrated a midpoint denaturation temperature of 43 degrees C in CD experiments. The 18-kDa peptide contained the tyrosine-rich globular domain of the molecule. The 9-kDa peptide was derived from the triple-helical end of the native molecule. Type X collagen was cleaved more rapidly by the vertebrate collagenase than was type II collagen in in vitro solution studies.
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PMID:Type X collagen contains two cleavage sites for a vertebrate collagenase. 300 23

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

Polymorphonuclear leukocytes (PMN) accumulating at inflammatory sites have the potential to degrade collagen by releasing the metalloproteinase collagenase (EC 3.4.24.7), which is stored within the specific granules of these cells in a latent, inactive, form. In order to elucidate the activation mechanism the latent enzyme (molecular weight 91,000) was purified from human PMN and incubated with the oxygen radical-generating system of xanthine oxidase (EC 1.1.3.22) and hypoxanthine. This coincubation resulted in the activation of the latent enzyme as assessed by the collagenolytic attack on human and bovine cartilaginous tissue. Two parameters for collagenolysis were used: loss of hydroxyproline-containing fragments, and mechanical measurements reflecting the stability of tissue specimens. Superoxide dismutase (EC 1.15.1.1) as well as catalase (EC 1.11.1.6) were capable of inhibiting the activation of latent PMN collagenase by the oxygen radical-generating system. The results indicate the hydroxyl radical to be the final oxidant responsible for the activation of latent PMN collagenase. Thus a new activation mechanism of latent collagenase is presented in this paper and discussed together with the potential relevance in pathophysiologic states of acute and chronic inflammation.
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PMID:Activation of latent collagenase from polymorphonuclear leukocytes by oxygen radicals. 303 4

A neutral metalloproteinase has been isolated and purified from adherent rheumatoid synovial cells in culture. This protease, named matrix metalloproteinase 3, (MMP-3) degrades gelatin, proteoglycan, fibronectin, type IV collagen, laminin, and the N propeptide of type I procollagen. It can be separated from MMP-2 (a potent gelatinase), and MMP-1, an interstitial collagenase. MMP-3 is released from cells as a proenzyme of 55 Kda. Activation by trypsin or organic mercurials produces 2 active species of 45 Kda and 28 Kda. The enzyme contains zinc as an intrinsic component and requires calcium for conformational stability. In concert, active MMP-1, -2, and -3 can destroy all significant structural proteins of joint structures.
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PMID:Matrix metalloproteinases 1, 2, and 3 from rheumatoid synovial cells are sufficient to destroy joints. 330 38


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