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)

Collagenase of human basal cell epithelioma was purified by sequential ammonium sulfate precipitation, Sephadex gel filtration and affinity chromatography on collagen-polyacrylamide gel. The collagenase, when partially purified, was found to have an approximate molecular weight of 50,000. The purified enzyme contained no caseinolytic activity. On polyacrylamide gel electrophoresis, the purified enzyme gave a single protein band. The purified collagenase cleaved native acid-soluble guinea pig skin collagen at 37 degrees C with a pH optimum of 8. The enzyme was inhibited by EDTA, cysteine, and human serum but not by soybean trypsin inhibitor. Heparin did not stimulate the enzyme activity. Purified collagenase reduced the specific viscosity of native acid-soluble guinea pig skin collagen to 50 per cent of its original value at 27 degrees C. Polyacrylamide gel disc electrophoresis of the reaction products showed bands corresponding to alphaA, betaA, and alphaB fragments. Electron microscopic examination of SLS aggregates of the reaction products showed that the cleavage site by the enzyme was at a point 75 per cent from the "A" end (TCA75) and 25 per cent from the "B" end (TCB25) of the collagen molecule.
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PMID:Collagenase of human skin basal cell epithelioma. 1 52

1. The addition of heparin to the culture fluid of mouse tibiae or calvaria did not cause any significant resorption of bone collagen or mineral. However, heparin (or analogue sulfated polyanions), enhanced greatly the amount of latent, trypsin-activatable collagenase (i.e. procollagenase) released by the bones in the medium without influencing that of directly active collagenase which was always very low. Heparin appeared to act by increasing the production of the enzyme which is immediately excreted. Procollagenase and collagenase are not stored in bone tissue, even under conditions where it is in active resorption. 2. Parathyroid hormone induced in the explants a resorption of both mineral and collagen that was inhibited by calcitonin. These hormones, however, had no influence on the release of procollagenase or collagenase either in the presence or in the absence of heparin. 3. Once activated, bone collagenase digested the collagen of the bone explants, and more extensively after their demineralization. Thus the latent collagenase that accumulates around non-resorbing bones has to be considered as a precursor, (and not as a residue), of active enzyme. 4. Active collagenase added to incipient cultures of bones disappeared with a half-life of 24 h. The lost enzyme could, however, not be reactivated by trypsin and thus was not transformed into latent procollagenase.
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PMID:Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin. 22 39

Studies on the effects of bovine aorta extracts on endothelial and smooth muscle cells cultured from the same tissue indicate they contain at least four separate molecular species capable of inhibiting cell growth. Two, heparin and a recently characterized dermatan sulfate-chondroitin sulfate proteoglycan, are large polyanions and inhibit the growth of both smooth muscle and endothelial cells, but require large amounts to induce this effect. The other two are low molecular weight molecules which inhibit only the growth of endothelial cells, one of which is a protease inhibitor which has been purified to homogeneity. The fourth and most potent is an as yet unidentified fraction distinguishable from the protease inhibitor. Heparin, as reported by others, and the proteoglycan also enhance collagenase activity. It would therefore appear that aorta contains several molecular species which have the potential to affect both invasive and proliferative processes.
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PMID:Growth regulators in connective tissues. II. Evidence for the presence of several growth inhibitors in aortic extracts. 53 30

Heparin is a potent inhibitor of arterial smooth muscle cell (SMC) migration and proliferation in vivo and in vitro. We propose that heparin affects these SMC functions by interfering with either the expression or the activity of secreted proteases required for cell movement. We have reported that heparin selectively inhibits the expression of tissue-type plasminogen activator in SMCs during mitogenesis. In this study we show that the gene expression of another kind of protease, interstitial collagenase, is induced by fetal bovine serum and is also suppressed by heparin. The inhibitory effect on the induced collagenase mRNA is specific to heparin-like molecules and does not depend on the anticoagulant activity of heparin. The induction of the collagenase gene depends on the protein kinase C pathway, since it can be induced by phorbol esters such as phorbol 12-myristate 13-acetate and blocked by inhibitors such as H-7 and staurosporine. In transient transfection assays with chloramphenicol acetyltransferase constructs containing the phorbol ester-responsive element introduced into baboon SMCs, heparin inhibits transcription induced by serum or phorbol 12-myristate 13-acetate. These results support the conclusion that, in primate SMCs, interstitial collagenase gene transcription mediated by the phorbol ester-responsive element is blocked by heparin.
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PMID:Heparin inhibits collagenase gene expression mediated by phorbol ester-responsive element in primate arterial smooth muscle cells. 131 15

We examined the interactions of the glycosaminoglycan, heparin, and recombinant human basic fibroblast growth factor (bFGF) on collagen synthesis in 21-day fetal rat calvariae. In calvariae treated for 96 h, heparin (25 micrograms/ml) and bFGF (10(-9) M) inhibited collagenase-digestible protein (CDP) labeling by 52 and 60% of control, respectively, and the combination further inhibited CDP labeling. Inhibition of CDP labeling by heparin (25 micrograms/ml) or bFGF (10(-9), 10(-8) M) was similar in the presence or absence of aphidicolin (30 microM) an inhibitor of cell replication. Heparin selectively inhibited CDP labeling in the osteoblast rich central bone but bFGF alone or in combination with heparin inhibited CDP labeling both in the periosteum and central bone. Heparin and bFGF alone decreased steady state levels of alpha 1(I)procollagen messenger RNA (mRNA) at 24 h and the combination further decreased mRNA levels. A high concentration of insulin-like growth factor-1 (IGF-1, 3 x 10(-8) M) reversed the inhibitory effect of heparin on DNA synthesis and CDP labeling. In contrast, IGF-1 could not reverse the inhibitory effects of bFGF on CDP labeling but enhanced the stimulatory effects of bFGF on thymidine incorporation into DNA. We conclude that the inhibitory effects of heparin and bFGF on CDP are independent of effects on cell replication. We further conclude that both heparin and bFGF inhibit collagen synthesis at a pretranslational site since they decreased procollagen mRNA levels in osteoblasts. However, the inhibition of collagen synthesis by heparin and bFGF appears to involve divergent pathways since exogenous IGF-1 could overcome the effect of heparin but not bFGF on collagen synthesis.
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PMID:The interaction of heparin and basic fibroblast growth factor on collagen synthesis in 21-day fetal rat calvariae. 137 12

To assess the effects of heparin on bone formation we measured [3H]proline incorporation into collagenase-digestible (CDP) and noncollagen protein (NCP), [3H]thymidine (TdR) incorporation into DNA, and DNA content in 21-day-old fetal rat calvaria cultured in BGJ medium with bovine serum albumin for 24-96 hours. Heparin at 5-125 micrograms/ml decreased TdR incorporation by 26-51% at 24 and 96 hours. At 96 hours, heparin 5, 25, and 125 micrograms/ml decreased [3H]proline incorporation into CDP by 41, 48, and 32%, respectively, with no significant change in NCP. To evaluate the possible role of PGE2 in these inhibitory responses, media PGE2 concentration was measured and the effects of heparin on CDP labeling and DNA synthesis were tested in the presence of indomethacin, piroxicam, and flurbiprofen to inhibit endogenous prostaglandin E2 (PGE2) production and in the presence of a high concentration (10(-7) M) of exogenous PGE2. Heparin did not alter PGE2 production at 24 hours but at 48 hours there was a significant reduction. At 96 hours, indomethacin (10(-6) M) inhibited [3H]-proline incorporation into CDP by 38% but had no effect on the labeling of NCP. Heparin had no further significant inhibitory effect in the presence of indomethacin. Piroxicam and flurbiprofen did not alter DNA content and had a smaller inhibitory effect than indomethacin on the labeling of CDP. Moreover, addition of heparin produced a further inhibition of CDP and DNA content and finally, heparin decreased CDP labeling by 71% in the presence of PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of heparin on bone formation in cultured fetal rat calvaria. 210 77

Constituents of the bone marrow microenvironment have the capacity to influence both normal and malignant hematopoietic cell behavior. For example, HL-60 human promyelocytic leukemia cells in vitro display a more mature phenotype when grown on a bone marrow stroma-derived matrix. To elucidate which component(s) of the stromal matrix is capable of modulating HL-60 cell phenotype, matrices were treated with a variety of chemicals and enzymes prior to being used in the differentiation assay. Treatment of matrices with collagenase, pronase, chondroitinase, or chloroform:methanol:ether could not abolish the differentiation-promoting activity of bone marrow stroma. In contrast, the activity was destroyed by alkali treatment (0.5 M NaOH for 18 h) or heparinase/heparitinase enzymes. Heparin added to cultures increased maturation of HL-60 cells as determined by esterase production, Fc rosette formation, and morphological appearance. Other stromal components such as laminin, fibronectin, collagen I, collagen IV, or chondroitin sulfate did not alter the HL-60 leukemia cell phenotype. Stroma-derived matrix material which labeled with [35S]sulfate and eluted on a DEAE ion-exchange column as a high ionic fraction in 1.5 M LiCl and 7.5% sodium dodecyl sulfate contained the active fraction. A heparan sulfate proteoglycan component isolated by polyacrylamide-agarose gel electrophoresis induced a more mature HL-60 phenotype, and digestion with heparinase/heparitinase in the presence of protease inhibitors abrogated the effects on HL-60 phenotype. We conclude that a heparan sulfate-associated fraction of the bone marrow matrix plays a key role in the regulation of leukemic cell maturation.
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PMID:A heparan sulfate-containing fraction of bone marrow stroma induces maturation of HL-60 cells in vitro. 214 Feb 91

Conditioned culture medium derived from Interleukin-I alpha-activated human articular chondrocytes contained both collagen- and proteoglycan-degrading activities. Preparations of soluble type I collagen and the cartilage collagens type II, IX, X and XI were all degraded when incubated with the conditioned culture medium at 35 degrees C. Fractionation of the enzymic activities using column chromatography with Ultragel AcA 34 and Heparin-Sepharose allowed the separation and identification of neutral proteinase, collagenolytic and proteoglycan-degrading activities. Eluant fractions which contained type I collagenase activity effectively degraded collagen type II, but these fractions did not correspond precisely with those which degraded collagen types IX, X and XI. These observations indicate that chondrocytes have the potential to produce a conventional interstitial type II collagenase together with other enzymes having some specificity for the minor collagens. Thus IL-1-activated chondrocytes produce a range of collagenolytic and proteoglycan-degrading enzymes which can process most of the structural components of the cartilage matrix.
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PMID:Degradation of cartilage collagens type II, IX, X and XI by enzymes derived from human articular chondrocytes. 217 Aug 28

Glycosaminoglycans specifically regulate the amount of calcium released from bone cultures; the mechanisms responsible for this regulation are not known. Media from glycosaminoglycan-stimulated bone organ cultures were analysed to determine (1) if specific calcium-releasing substances were selectively produced, and (2) if protein synthesis was differentially affected by glycosaminoglycans. Chondroitin sulphate B, hyaluronic acid and keratan sulphate at 100 micrograms/ml significantly increased prostaglandin release when compared with control cultures. In combination with suboptimal concentrations of PTH, chondroitin sulphate B, heparin and keratan sulphate significantly stimulated prostaglandin release. When indomethacin was included in the test assays, the stimulated prostaglandin release was abolished. Heparin-treated cultures released the greatest percentage of latent collagenase activity followed by hyaluronic acid-treated cultures. Organ cultures treated with heparin and PTH amount of active collagenase. Stimulation increased interleukin-1 above control levels but with no significant difference among the glycosaminoglycans except for keratan sulphate cultures with which had the greatest amount of interleukin-1. Collagen protein decreased between 48 and 72 h under both control and experimental conditions. Examination of the predominant [35S]-methionine labelled proteins revealed that prostaglandin E2 treatment resulted in a relative shift in labelling to higher molecular-weight proteins as time in culture increased (up to 144 h). After 48 h, when equal amounts of labelled protein were analysed, there was a predominance in labelling of a 200,000 Da protein in the prostaglandin-treated cultures. These findings demonstrate that modulation of calcium release by glycosaminoglycans results in the selective release of molecules capable of stimulating calcium release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The induction of specific metabolic alterations in mouse calvarial organ cultures by glycosaminoglycans. 217 70

A comparison was made between collagenase-dispersed guinea-pig atrial and ventricular tissues. Heparin containing cells were stained with alcian blue at pH 2.2, and counted by an automated technique (Technicon H6000). The cells were challenged with the specific antigen (ovalbumin), with antisera to guinea-pig IgG (non-subclass specific), IgG1 and IgG2, and the calcium ionophore A23187. Histamine release was measured by an automated spectrofluorometric technique, and leukotriene C4 was measured by radioimmunoassay. All of the following parameters were higher in the atrial than in ventricular cells (mean ratio and SEM of atrial: ventricular mast cell parameters in parenthesis): Histamine content/g wet tissues (3.32 +/- 0.71:1) (p less than 0.05), Absolute mast cell number as a proportion of total cell count (3.75 +/- 1.64:1), Histamine release induced by antigen (significant in one out of four experiments), anti-IgG (significant in three out of four experiments), anti-IgG1 (significant in two out of four experiments), and anti-IgG2 (higher but not statistically significant). Ionophore A23187 gave an inconsistent histamine release pattern: significantly higher release from atria in five treatments (different concentrations in different experiments), and higher ventricular release in three. Significantly more leukotriene C4 was released by antigen and the ionophore A23187 (mean of 3-5 treatments), but not with anti-IgG.
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PMID:Comparison of the response of mast cells in guinea-pig cardiac atria and ventricles. 243 72


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