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)

1. Explants of dog gingiva, maintained in culture for 9 days in the absence of serum, released a collagenase (EC 3.4.24.3) into the medium. The yield of active enzyme reached a maximum after 5-8 days with concomitant release of collagen degradation products from the explants. 2. The enzyme attacked undenatured collagen in solution at 25 degrees C resulting in a 58% loss of specific viscosity and producing the two characteristic products TCA(3/4) and TCB(1/4). Electron microscopy of segment-long-spacing crystallites of these reaction products showed the cleavage locus of the collagen molecule at interband 40. 3. Optimal enzyme activity was observed over the pH range 7.5-8.5 and a molecular weight of approximately 35,000 was derived from gel filtration studies. EDTA, 1,10-phenanthroline, cysteine and dithiothreitol all inhibited collagenase activity. Proteoglycan derived from porcine and human cartilage did not inhibit the enzyme. 4. The enzyme was inhibited by the dog serum proteins alpha2-macroglobulin and a smaller component of molecular weight approximately 40,000. This small component was purified by column chromatography utilising Sephadex G-200, DEAE A-50, and G-100 (superfine grade). Agarose electrophoresis of the purified component showed it to represent a beta-serum protein. alpha1-Antitrypsin did not inhibit the enzyme. 5. The physiological importance of the natural serum inhibitors and gingival collagenase are discussed in relation to latent enzyme and periodontal disease.
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PMID:Characterization and serum inhibition of neutral collagenase from cultured dog gingival tissue. 7 61

Platelet degranulation can result in the release of a variety of factors which are chemotactic, mitogenic, and angiogenic, making platelets extremely important in the regulation of the repair process. This study examines how various types of root surfaces affect platelet deposition and the release of serotonin from dense granules. In addition, experiments were performed to evaluate the effects of the cyclo-oxygenase inhibitor, indomethacin, on platelet deposition and dense granule release. Roots from freshly extracted teeth from sites with periodontal disease (PD) and from healthy sites were sectioned and had the following surface conditions: 1) periodontal ligament present; 2) PD; 3) PD, root planed; 4) PD, root planed and demineralized; and 5) condition 4 treated with collagenase. In addition, rabbit calcaneal tendon collagen was used. All samples were incubated with platelets labeled with both 111Indium and 14C serotonin, with and without the addition of indomethacin. It was observed that the greatest number of platelets deposited on the tendon collagen. Furthermore, serotonin release occurred on all samples except PD and indomethacin partially inhibited platelet deposition on all samples except tendon collagen. Finally, indomethacin inhibited serotonin release on all surfaces. These results suggest that attachment of platelets to the root surface is facilitated by metabolism through the cyclo-oxygenase pathway and that limited platelet deposition can occur in the absence of dense body release.
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PMID:In vitro platelet serotonin secretion and inhibition on variously treated root surfaces. 131 1

In view of the important role of fibroblast-type collagenase in the pathogenesis of periodontal disease (PD), we investigated the expression of this metalloproteinase in primary cultures of non-stimulated fibroblasts dissected from gingival tissues of patients with generalized moderate and localized severe chronic adult PD. Enhanced hybridization signals for collagenase RNA were observed in 8/8 PD-cases when compared with equivalent RNA amounts extracted from normal fibroblasts. Since both the proto-oncogene c-fos and the "early growth response" gene egr-1 might be involved in the transcriptional regulation of the collagenase gene expression in vivo, we also compared the relative expression of both potential transcriptional factors with collagenase RNA in the same fibroblast cytoplasmic extracts. Hybridization signals indicated elevated RNA amounts for c-fos in 8/8 PD-cases and for egr-1 in 7/8 PD-cases when compared with the cells from non-inflamed tissue. In periodontitis gingival tissue specimens, immunolocalization of collagenase could be confirmed in fibroblasts, macrophages and epithelial cells in situ. Collagenase label was not widely distributed within the tissues, but concentrated at the interface between epithelium and connective tissue. The data provide the first evidence that gingival fibroblasts producing elevated levels of collagenase RNA amounts express also c-fos and egr-1 indicating a crucial role for both genes in cellular proliferation and collagenase expression in gingival and periodontal tissue destruction in vivo.
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PMID:Expression of collagenase and potential transcriptional factors c-fos and egr-1 in periodontal gingival fibroblasts. 138 1

The study aimed to investigate the effects of n-butyrate and propionate on the proliferation and viability of human endothelial cells in culture. Proliferation was assessed by a 24-hour bromodeoxyuridine pulse labelling and immunoperoxidase method and viability was assessed by a colorimetric viability (MTT) assay. Endothelial cells were isolated from human umbilical vein by collagenase digestion. Experiments were performed on 96-well plates and cultures were exposed to different concentrations of n-butyrate and propionate for 2 days. n-butyrate and propionate caused significant reductions in the proliferation of endothelial cells at concentrations of 1.25 mM and 10 mM respectively (p less than 0.05); the reduction in proliferation was dose-dependent for both agents. n-butyrate was a more potent inhibitor of proliferation than propionate. However, there were no significant effects on the viability of the cells with both agents up to the highest concentrations tested (25 mM). The data indicate that n-butyrate and propionate inhibit endothelial cell proliferation which may contribute to the pathogenic effects of dental plaque in periodontal disease.
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PMID:Inhibition of human endothelial cell proliferation in vitro in response to n-butyrate and propionate. 140 79

Traditional clinical variables of periodontal pathology have only limited value as indicators for future disease progression in patients with adult periodontitis. Consequently, other aspects of the periodontal lesion are being examined for their diagnostic utility. Analysis of the host response in gingival crevicular fluid (GCF) is among the most intensely studied of these new diagnostic approaches. Specific indicators of the humoral immune response, cellular immune response, and acute inflammatory response have been identified in GCF. The relationship of indicators of the humoral immune response to active periodontal disease is equivocal. Specific indicators of the cellular immune response in GCF may ultimately prove to be important diagnostically, but the relationship of any specific marker to active periodontal disease has not been reported. In contrast, the acute inflammatory response in GCF has been extensively studied and a number of factors appear to be associated with an increased risk for future disease progression. Indicators of enhanced polymorphonuclear leukocyte activity, (lysosomal beta-glucuronidase, lysosomal collagenase), prostaglandin E2, and an indicator of acute tissue destruction (the cytoplasmic enzymes aspartate aminotransferase) have been associated with the occurrence of clinical attachment loss. An example of the application of a GCF marker in a periodontitis clinical trial is provided by describing the relationship of lysosomal beta-glucuronidase in GCF at baseline and 2 weeks following root planing and scaling to the occurrence of disease activity during the following 6 months. Persistently elevated levels of this enzyme were related to clinical attachment loss. The positive, negative, and total predictive values for beta-glucuronidase as an identifier of clinical attachment loss were 86%, 71%, and 76%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The host response in gingival crevicular fluid: potential applications in periodontitis clinical trials. 147 31

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

Bacteroides gingivalis is associated with various forms of periodontal disease. To assess the role of the immune response in modulating B. gingivalis-associated periodontal disease, the effect of immunization of B. gingivalis-induced periodontal bone loss was evaluated in gnotobiotic rats. Male Sprague-Dawley rats immunized with various doses of whole cells or sham-immunized with incomplete Freund's adjuvant were monoinfected with B. gingivalis in carboxymethylcellulose by gavage. Two additional groups served as either sham-immunized or untreated germ-free controls. Forty-two days after infection, all rats were killed, periodontal bone level was assessed morphometrically and radiographically, and gingival proteinase (mammalian collagenase and acid cathepsin) activity was assessed biochemically. B. gingivalis was present in oral samples from all monoinfected rats, and no contaminating bacteria were detected in any oral or fecal sample. Animals immunized with B. gingivalis cells had elevated serum and saliva antibodies to whole cells and partially purified fimbriae from B. gingivalis. Infected sham-immunized rats had significantly more periodontal bone loss than noninfected controls, whereas the periodontal bone level in infected rats immunized with 10(10) B. gingivalis cells was similar to that of the noninfected controls. The activities of gingival collagenase and cathepsin B and L were high in sham-immunized infected rats and low in all other animal groups. In conclusion, it is possible to reduce B. gingivalis-induced periodontal tissue loss in gnotobiotic rats by immunization.
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PMID:Periodontal bone level and gingival proteinase activity in gnotobiotic rats immunized with Bacteroides gingivalis. 168 84

During the past few years, a considerable number of studies have examined different aspects of the host response in gingival crevicular fluid (GCF), including the relationship of specific markers to the active phases of periodontal disease. Various indicators of the acute inflammatory response (the lysosomal enzymes beta-glucuronidase and collagenase, the cytoplasmic enzyme aspartate aminotransferase, and the arachidonic acid metabolite PGE2) have been shown to be associated with clinical attachment loss in chronic adult periodontitis in man and experimental periodontitis in animal models. In contrast, the relationship of indicators of the humoral immune response in GCF to active periodontal disease is equivocal. Furthermore, a number of indicators of the cellular immune response have been identified recently in GCF (i.e., Interleukin-1 alpha, IL-1 beta, tumor necrosis factor-alpha), but their relationship to active phases of periodontal disease have not been studied. The polymorphonuclear leukocyte (PMN) is the cellular hallmark of acute inflammation. Evidence from the GCF studies suggests that hyperreactivity of these cells plays a critical role in the active phases of some forms of periodontal disease. Metabolic activation of PMN can be associated with a number of potentially destructive reactions. The major effector mechanism for tissue destruction that can be specifically identified with the PMN is the synergistic effect of the release of PMN proteases and the generation of reactive oxygen metabolites by these cells. Priming of the PMN, where the PMN response is enhanced by agents that do not initiate the response, may be an important mechanism for PMN activation in the crevicular environment; for example, cytokines such as IL-1 beta and TNF-alpha, and lipopolysaccharides released from subgingival Gram-negative bacteria, can serve this function. The hypothesis proposed here argues that in addition to the severe forms of periodontal disease that have been associated with qualitative or quantitative PMN defects, tissue destruction in the periodontum can be observed with hyperreactivity of these cells. These differing conclusions do not create a dilemma, but may represent opposite ends of a balance that is no longer in equilibrium.
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PMID:Host mediators in gingival crevicular fluid: implications for the pathogenesis of periodontal disease. 173 70

Human gingival fibroblasts were used to study the effects of increasing concentrations of glucose on protein, collagen and glycosaminoglycan (GAG) synthesis. GAG-synthesis was measured as incorporation of 3H-glucosamine into pronase-resistant macromolecules and collagen synthesis was evaluated by 3H-proline incorporation into collagenase-sensitive protein. Incubation of the fibroblasts with glucose concentration ranging from 5 to 50 mM resulted in a dose-dependent reduction of collagen synthesis; labeled collagen in the culture medium was reduced to 60% of the control incubation (5mM glucose) when incubated with 50 mM glucose for 72 h. Cell-associated radioactivity was decreased to 80% under the same conditions. Although 3H-glycosamine incorporation into GAGs was reduced by increasing glucose concentrations (5 to 20 mM), protein synthesis and cell number were not influenced under the same conditions, as was also the case with distribution of macromolecules in the GAG fractions. The importance of these in vitro results to the incidence of chronic inflammatory periodontal disease in diabetic patients is discussed.
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PMID:Influence of high glucose concentrations on glycosaminoglycan and collagen synthesis in cultured human gingival fibroblasts. 206 19

Two test teeth, anteriors with greater than or equal to 6 mm deep periodontal pockets from each of 10 patients with advancing periodontitis were included in this study. The clinical signs of advancing periodontitis, generalized moderate to deep pockets and to severe loss of alveolar bone, were observed in young adult. There have been several reports on factors, which reflect the conversion clinically from infection by highly pathogenic plaque bacteria to a from of periodontitis displaying relatively rapid loss of clinical attachment. The purpose of this investigation was to detect parameters in fluid, which could leak from the underlying inflamed connective tissue into the gingival crevice, and which could shown correlatively the progressive variations of periodontal disease by recurrent acute stage. In order to determine active disease sites and to monitor guantitatively response to therapy or to measure degree to susceptibility of future breakdown. Examinations on following parameters at pre- and post- periodontal treatment stages were carried out. Endotoxin, collagenase, alkaline phosphatase, beta-glucuronidase, interleukin-1 alpha, IgG antibody levels to Bacteroides gingivalis, Bacteroides intermedius were measured in gingival exudate samples, which were collected by the microtips technique from periodontal pockets. The following results were obtained: 1) Considering the effect of periodontal therapy, pathogenic responses on total colony forming unit (CFU), interleukin-1 alpha and changes of endotoxin and beta-glucuronidase levels after the treatment have indicated that specific changes in humoral responses. 2) There was not significant relation between alkaline phosphatase, collagenase, IgG antibodies level to Bacteroides gingivalis, Bacteroides intermedius and responses in active and also inactive disease sites. 3) This study has been resulted in the development of diagnostic techniques which requires strict criteria on the disease activity of the periodontal disease very specific in order to permit a more scientific approach to the care of periodontitis patients and to speculate the prognosis of the patients after the treatment.
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PMID:[Changes of factors on disease activity in advancing periodontitis]. 213 9


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