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)

Phosphorylation events are major regulatory mechanisms of signal transduction pathways that control cell growth and differentiation. The potential involvement of serine/threonine-specific phosphoprotein phosphatases in pathways that regulate gene expression was analyzed. By use of okadaic acid, an inhibitor of protein phosphatases 1 (PP-1) and 2A (PP-2A), we present evidence that expression of distinct members of the jun family of genes, c-jun, junB, and junD, are regulated differentially by serine/threonine-specific phosphoprotein phosphatases. Treatment of cells with okadaic acid induces the expression of junB, and to a lesser extent c-jun, but has only a marginal effect on junD expression. This induction involves transcriptional as well as post-transcriptional mechanisms. An analysis of defined elements in different promoters suggests that serine/threonine phosphoprotein phosphatases are involved in the regulation of the c-jun and the collagenase 12-O-tetradecanoyl phorbol-13-acetate (TPA) response element (TRE) as well as the c-fos serum response element (SRE). Since inhibition of PP-1 and PP-2A leads to increased proto-oncogene expression, our results further support the view that certain protein phosphatases might act as negative regulators of growth.
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PMID:Differential regulation of jun family gene expression by the tumor promoter okadaic acid. 166 87

Yeast cultures of Histoplasma capsulatum var. duboisii and H. capsulatum var. capsulatum in collagen containing defined, semi-defined and complex media produced extracellular collagenolytic proteinases, assayed using 4-phenylazo-benzyloxycarbonyl-L-propyl-L-leucyl- glycyl-L-propyl-D-arginine, a specific collagenase substrate. Significant levels of hydroxyproline were measured in the cultures and clear zones of hydrolysis were produced in collagen buffer agar by the crude enzyme preparations. Hydrolysis of casein and bovine serum albumin at pH 8 suggests the presence, in the crude enzymes, of multiple proteinases rather than a collagenase with broad substrate specificity since collagenolytic activity was not detected at pH 5 and above. Collagenolytic activities in the crude enzymes of both fungi were optimal at pH 4, 40 degrees C and were inhibited by EDTA, phosphoramidion and aprotinin indicating a metallo-serine nature. The molecular weights, estimated by column chromatography, were both 17 kD. The enzymes probably constitute a shared antigen. A probable role in the pathogenesis of histoplasmosis is discussed.
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PMID:Production of extracellular collagenolytic proteinases by Histoplasma capsulatum var. duboisii and Histoplasma capsulatum var. capsulatum in the yeast phase. 166 20

Proteolytic enzymes, particularly collagenase, are involved in development of eye cornea chronic ulcers. Analysis of lacrimal fluid obtained from the patients enabled to find not only the collagenase activity but and serine enzymes exhibiting BAEE esterase activity. Plasmin, blood plasma and tissue kallikreins regulated permeability of capillaries in conjunctiva and lacrimal gland as well as they activated latent collagenase. Studies of BAEE esterase activity in lacrimal fluid of the patients are required for prescription of adequate pathogenetic treatment.
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PMID:[Proteolytic enzymes of the lacrimal fluid as pathogenesis factors of chronic corneal ulcer]. 169 16

Using competitive ELISA it was found that chondroitin proteoglycans from the skin of squid, which is a primitive organism, are reactive with the HNK-1 monoclonal antibody and that all HNK-1 epitopes of the proteoglycans were present only on their oligosaccharides. Although of the presence of appreciable amounts of glycine, serine and glutamic acid and the absence of hydroxyproline, the proteoglycans were degraded by collagenase and other proteolytic enzymes.
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PMID:Presence of the HNK-1 epitope (3-sulfoglucuronic acid) on oligosaccharides from squid skin chondroitin proteoglycans and degradation of proteoglycans by proteolytic enzymes. 172 51

We have investigated the surface phenotypic profile of murine lung macrophages in frozen tissue sections, in single-cell suspensions obtained by endobronchial lavage, and in collagenase digests of parenchymal lung tissue, using a panel of monoclonal antibodies directed against pan macrophage markers and antigens present on distinct lymphoid-associated macrophage subpopulations. Our results indicate that lung macrophages from specific pathogen-free (SPF), lipopolysaccharide (LPS) hyporesponsive C3H/HeJ mice are relatively homogeneous no matter what lung tissue compartment they are obtained from. Their predominant surface phenotype was F4/80weak, M1/70-, MOMA-2+, NLDC-145+, MOMA-1+, SER-4+, which resembles the pattern of expression by lymphoid macrophages rather than representative tissue macrophages such as those found in the peritoneal cavity. These results are consistent with the current paradigm that lung macrophages, like lymphoid macrophages, play an important immunoregulatory role within their microenvironment.
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PMID:The surface phenotypic characterization of lung macrophages in C3H/HeJ mice. 178 23

The mechanism of proteoglycan (GAG) loss from rat femoral articular cartilage (FHC) induced by recombinant human interleukin-1 beta (rhIL-1 beta) in vitro has been investigated. The metalloproteinase inhibitor 1,10-phenanthroline, the serine proteinase inhibitor N alpha-p-tosyl-l-lysine chloromethyl ketone (TLCK), the activator of latent metalloproteinase p-aminophenylmercuric acid (APMA), and an inhibitory metalloproteinase substrate analogue U27391 were tested for their ability to modulate rhIL-1 beta-induced GAG loss and GAG synthesis ([35S]O4 uptake) inhibition. As expected 1,10-phenanthroline inhibited GAG loss, however [35S]O4 incorporation was significantly reduced. TLCK was without effect, and APMA inhibited both parameters. U27391 reversed both the inhibition of [35S]O4 incorporation and GAG loss. It is concluded that the adverse effects on proteoglycan metabolism explain the inhibitory actions of 1,10-phenanthroline and APMA, whilst the action of TLCK may indicate that serine proteinases are not involved in the activation of latent metalloproteinase. U27391 exhibited chondroprotective activity and confirmed the induction of either metalloproteinases such as stromelysin or collagenase by rhIL-1 beta.
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PMID:Investigation of the role of metalloproteinases in recombinant human interleukin-1 beta-induced degradation of rat femoral head cartilage. 179 2

Human mononuclear phagocytes express an array of serine and metal dependent proteinases that are under complex developmental control and are also highly regulated by physiologic and pharmacologic stimuli. Monocytes contain the intracellular serine proteinases, elastase and cathepsin G, but have little metalloproteinase secretory capacity. Macrophages, on the other hand, produce predominantly metalloproteinases. Phorbol induced differentiation of promonocyte-like U937 cells into more mature mononuclear phagocytes results in transcriptional suppression of cathepsin G and temporally delayed onset of collagenase transcription. Mature macrophages upregulate metalloproteinase synthesis in response to lipopolysaccharide and phorbol myristic acetate; expression is downregulated with interferon gamma and dexamethasone. Thus, during the development of the mononuclear phagocyte, stores of serine proteinases are replaced by regulated secretion of metalloproteinases. These alterations may reflect changing roles of these cells in extracellular matrix degradation.
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PMID:Proteinases secreted by human mononuclear phagocytes. 190 75

Transforming growth factor beta (TGF-beta) is usually associated with matrix formation and tissue repair; in contrast, cellular expression of the serine proteinase, urokinase-type plasminogen activator (u-PA) is often correlated with tissue remodeling, as well as with cell migration and transformation. We report here that purified recombinant human TGF-beta (greater than or equal to 300 pg/ml) can stimulate rapidly (within 2 h) the u-PA activity of nonrheumatoid synovial fibroblast-like cells. As for interleukin 1 (IL-1), u-PA mRNA levels are raised in response to TGF-beta, but unlike IL-1, no increase in prostaglandin E2 levels occurs. In contrast to a number of other examples in the literature, in which these two cytokines have opposing actions, TGF-beta can potentiate the action of optimal concentrations of IL-1 in enhancing u-PA expression. These effects of TGF-beta are similar to those of all-trans-retinoic acid. In addition, synovial fibroblast DNA synthesis was stimulated by TGF-beta. Because TGF-beta has been detected in the synovia of patients with rheumatoid arthritis and has been shown to reduce the collagenase levels and proliferation of synovial fibroblast-like cells, it has been proposed by others to be involved beneficially in the reparative processes occurring in arthritic lesions. However, on the basis of our findings, we propose alternative functions for this cytokine--namely, roles in the destructive events as well as in the synovial hyperplasia observed in rheumatoid joints.
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PMID:Transforming growth factor beta stimulates urokinase-type plasminogen activator and DNA synthesis, but not prostaglandin E2 production, in human synovial fibroblasts. 190 92

Interstitial collagenases (matrix metalloproteinase-1, EC 3.4.24.7), isolated from extracts of inflamed human gingiva, gingival crevicular fluid and saliva were characterized for their molecular weight, proteolytic and non-proteolytic activation and substrate specificity against soluble collagen types I, II and III. All three collagenases had Mr of 70 K. The enzymes existed predominantly in a latent form that could be activated by aminophenylmercuric acetate, gold thioglucose and hypochlorous acid. Among serine proteases tested, trypsin, chymotrypsin, neutrophil cathepsin G and a combination of trypsin and human gingival fibroblast prostromelysin activated gingival and salivary interstitial collagenases. Plasmin and plasma kallikrein, however, were relatively ineffective activators. The collagenases degraded soluble type I and II collagens at apparently equal rates but considerably faster than they did type III collagen. These findings suggest that the characteristics of interstitial collagenases found in inflamed human gingiva, gingival crevicular fluid and saliva are consistent with those of human neutrophil interstitial collagenase rather than the fibroblast-type interstitial collagenase. Thus, neutrophils are suggested to be the main source of such enzymes in inflamed human gingiva, crevicular fluid and saliva during adult periodontitis.
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PMID:The role of gingival crevicular fluid and salivary interstitial collagenases in human periodontal diseases. 196 17

The differentiation of F9 and PSA-1 embryonal carcinoma cells to embryoid bodies composed of a mixture of parietal and visceral endoderm was accompanied by changes in their secretion of metalloproteinases. Differentiation was induced by retinoic acid and dibutyryl cyclic AMP (for F9 cells) or by removing cells from a substrate of feeder cells to alter cell-cell interaction and adhesion (for PSA-1 cells). The embryoid bodies attached to gelatin-coated dishes, and the parietal endoderm cells spread out over the matrix. The differentiated cells secreted specific gelatin- and casein-degrading proteinases, including enzymes that comigrated with proenzyme forms of collagenase and stromelysin. Total proteinase activity as well as specific collagenase activity increased with the time of differentiation. All of the gelatin- and casein-degrading proteinases detectable by substrate gel zymography were inhibited by inhibitors of metalloproteinases but not by inhibitors of serine or cysteine proteinases, indicating that they were metalloproteinases. Both cell lines showed increased collagenolytic activity, which was activated by treatment with plasmin. In addition, both cell lines showed increased secretion of specific metalloproteinase inhibitors, including tissue inhibitor of metalloproteinases, with differentiation. Analysis of mRNA from undifferentiated and differentiated F9 cells by RNA blot analysis or reverse transcription coupled with the polymerase chain reaction showed that increased expression of genes for collagenase, stromelysin and tissue inhibitor of metalloproteinases is associated with differentiation of these cells. These results suggest that the expression of extracellular matrix-degrading metalloproteinases and their inhibitors is developmentally regulated during the differentiation and spreading of the parietal endoderm.
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PMID:Expression of extracellular matrix-degrading metalloproteinases and metalloproteinase inhibitors is developmentally regulated during endoderm differentiation of embryonal carcinoma cells. 208 60


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