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)

The effects of cadmium and zinc on bone resorption were investigated using fetal mouse calvaria organ culture. Cadmium treatment (0.5 microM) stimulated bone resorption in fetal mouse calvaria via prostaglandin E2 production. Concomitant treatment of zinc with cadmium prevented bone resorption by cadmium in a dose-dependent manner of zinc. The zinc treatment also prevented the stimulation of prostaglandin E2 production by cadmium. ID50 of zinc for bone resorption showed high similarity to that for prostaglandin E2 production (1.2 microM and 1.6 microM, respectively). To simplify the system, we used osteoclast-enriched and osteoblast-enriched cell populations obtained from mice calvariae by collagenase digestion method. Prostaglandin E2 was produced in osteoblast-enriched cell culture more than in osteoclast-enriched cell culture. Cadmium stimulated prostaglandin E2 production in osteoblast-enriched cell culture, but not in osteoclast-enriched cell culture. Zinc also prevented the stimulatory effect of cadmium on prostaglandin E2 production in osteoblast-enriched cell culture. Zinc partially, but significantly, inhibited cadmium-accumulation in both calvaria and osteoblast-enriched cell culture. These results strongly suggest that zinc prevents cadmium-induced prostaglandin E2 production and bone resorption through the interaction between the two metals on osteoblasts involved in the inhibition of cadmium-accumulation.
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PMID:Preventive effect of zinc against cadmium-induced bone resorption. 234 56

Interleukin-1 (IL-1) is secreted by macrophages, macrophage-like cells (e.g. Langerhans cells) and by astrocytes, keratinocytes, fibroblasts or natural killer cells. IL-1 is directly involved in the activation of helper T lymphocytes. However, it has been shown that IL-1 also induces release of collagenase and prostaglandins by fibroblasts. Furthermore, injections of IL-1 into animals are followed by fever, leukocytosis, increased serum concentrations of fibrinogen, serum amyloid A and haptoglobin, and decreased levels of iron and zinc. IL-1 has been extracted from experimental granuloma and from tissues of animals with endotoxinemia. Synovial fluids from patients with osteoarthritis contain significant amounts of IL-1. All in all, IL-1 may be ultimately involved in the development of fever and fibrosis, in the destruction of joints and the activation of T lymphocytes during inflammatory processes.
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PMID:[Interleukin 1]. 241 45

The effects of proteases on air-space clearance (AC) of small ([14C]sucrose, 342 daltons) and large (125I-neutral dextran, 70,000 daltons) solutes were studied in isolated, fluid-filled hamster lungs that were perfused in a nonrecirculating system. When instilled into the air spaces, porcine pancreatic elastase (0.1-0.4 mg/ml) and bovine pancreatic trypsin (BPT) (0.5-2.0 mg/ml), but neither Clostridium histolyticum collagenase (5.0 mg/ml) nor phenylmethylsulfonyl fluoride-inactivated BPT caused large increases in the AC of both tracer molecules. BPT-induced solute clearance was further characterized functionally and morphologically. The functional characteristics of solute AC under steady-state conditions did not indicate that transepithelial transport was diffusion-limited. Inhibition by millimolar concentrations of Zn2+ and by lung cooling, along with electron microscopic studies employing horseradish peroxidase as a macromolecule tracer, were consistent with epithelial solute transport by a vesicular mechanism (transcytosis). Solute transport from the interstitial compartment to the lung exterior was shown to occur via two pathways. By unknown mechanisms BPT caused small amounts of water to flow through an incompletely identified, extravascular pathway. In BPT-exposed lungs efflux of 125I-dextran 70 occurred almost exclusively through this pathway, whereas [14C]sucrose was transported to the lung exterior partly through this same pathway and partly through the vasculature. The large differences in the diffusion coefficients of the two tracers may have accounted for these observed patterns of solute efflux from the lung. The possible significance of our findings to the pathogenesis of experimental emphysema are discussed.
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PMID:Effect of proteolytic enzymes on transepithelial solute transport. 243 Sep 29

Feeder-cell-independent serially propagating keratinocytes from rat oral mucosa (tongue) dissolved reconstituted type I [3H]collagen fibrils, although rather slowly. Analysis of the conditioned medium from such cultures revealed secretion of a Mr = 65,000 collagenase which remained almost entirely latent in the absence of exogenous protease activity. Addition of trypsin (0.1-1.0 microgram/ml) or plasmin (1.0-4.0 micrograms/ml) resulted in substantial acceleration of the collagenolytic process in stimulated secretion of latent collagenase and, at higher concentrations, in conversion of the latent enzyme to the catalytic form. The keratinocyte collagenase was indistinguishable from interstitial, fibroblast-type collagenases by several criteria including: cleavage of native type I collagen in solution at the characteristic collagenase-sensitive locus at 22 degrees C and dissolution of reconstituted type I collagen fibrils at 35 degrees C; activation by trypsin and by organomercurials and inhibition by Zn2+ and Ca2+ chelators; and cross-reaction with antibody to fibroblast-type procollagenase. Expression of collagenolytic activity in keratinocyte cultures was effectively regulated by cell density. The activity (on a per cell basis) was maximal at 10-20% confluence and was more than 95% "contact-inhibited" at subconfluent and early confluent densities (2-4 X 10(5)/cm2). Our findings show that mucosal keratinocytes possess a potent enzymatic apparatus for degradation of interstitial collagen fibrils which includes a classical vertebrate collagenase.
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PMID:Degradation of type I collagen by rat mucosal keratinocytes. Evidence for secretion of a specific epithelial collagenase. 243 24

Depolarization of follicle-enclosed oocytes of Xenopus laevis obtained from some donors elicits, in addition to other responses, a fast transient outward current. After holding the membrane potential at -100 mV this response begins to be activated by depolarizations to around -30 mV, and increases progressively as the voltage is raised further. A striking characteristic is that the current recovers only slowly (several seconds) from inactivation following a depolarizing pulse. Because of its outward direction and insensitivity to removal of extracellular chloride or addition of tetrodotoxin, the current probably arises largely through a flux of potassium ions. The current was abolished after treatment of oocytes with collagenase to remove enveloping cells, and although it was blocked by barium and zinc ions, tetraethylammonium was relatively ineffective. In addition, the potassium current was unaffected by 5 mM manganese, suggesting that it does not arise as a consequence of an influx of calcium into the oocyte.
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PMID:Transient potassium current in native Xenopus oocytes. 245 25

The modulation of the production of collagenase by an epithelial cell line derived from a spontaneously arising rat mammary carcinoma has been studied. The cell line, BC1, was grown permanently under defined serum-free conditions, thus avoiding the poorly characterized and variable effects of serum on collagenase production. Piperazine-N,N'-bis-(2-ethanesulfonic acid) (Pipes), retinoic acid and cytochalasin B all stimulated collagenase secretion, while dexamethasone inhibited it and progesterone, prolactin, prostaglandin E2, and estrogen had no effect. This profile of response to exogenous compounds was distinct from that of cells of mesenchymal origin and from human keratinocytes. For the production of large quantities of collagenase, culture medium was supplemented with Pipes (30 mM, pH 6.8), and retinoic acid (1 microM, on alternate feeds). The collagenase secreted by BC1 cells grown under these conditions was latent and had a molecular mass of 59 kDa. Treatment of the 59 kDa form with trypsin or APMA caused a progressive decrease in molecular mass via 54 kDa and 52 kDa intermediates, to a 48 kDa form. This form was purified to electrophoretic homogeneity by heparin-Sepharose, zinc-chelate-Sepharose, and Sephacryl S-200 chromatography. Five milligrams of purified collagenase were recovered per litre of culture medium.
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PMID:The collagenase produced by neoplastic rat epithelial cells: modulation of secretion, molecular weight characteristics, and purification. 254 Apr 4

Dithizone, a zinc chelating agent, is known to selectively stain the islets of Langerhans in the pancreas. In the present study, we have used this stain to aid the identification of islets in material obtained by collagenase digestion of human pancreas. Islets were shown to rapidly and reversibly stain red on incubation with dithizone solution. Tissue selected on the basis of dithizone staining was shown to contain insulin-positive cells and to accumulate insulin in the medium during a subsequent period in tissue culture. Experiments with rat islets indicated that the dithizone treatment had no effect on insulin release in tissue culture, on acute responses to stimulatory glucose concentrations or on the insulin content of cells. These results suggest that dithizone staining can assist in the identification of islets from the human pancreas and may prove to be a useful tool in developing techniques for the large scale isolation of functionally intact human islets.
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PMID:Supravital dithizone staining in the isolation of human and rat pancreatic islets. 254 5

On purification, human fibroblast collagenase breaks down into two major forms (Mr22,000 and Mr 27,000) and one minor form (Mr 25,000). The most likely mechanism is autolysis, although the presence of contaminating enzymes cannot be excluded. From N-terminal sequencing studies, the 22,000-Mr fragment contains the active site; differential binding to concanavalin A shows the 25,000-Mr fragment is a glycosylated form of the 22,000-Mr fragment. These low-Mr forms can be separated by Zn2+-chelate chromatography. An activity profile of this column, combined with data from substrate gels, indicates no activity against collagen in the 22,000-Mr and 25,000-Mr forms, but rather, activity casein and gelatin. The 27,000-Mr form has no activity. The 22,000/25,000-Mr form can act as an activator for collagenase in a similar way to that reported for stromelysin. The activity of the 22,000/25,000-Mr form is not inhibited by the tissue inhibitor of metalloproteinases (TIMP). The 27,000-Mr C-terminal part of the collagenase molecule therefore appears to be important in maintaining the substrate-specificity of the enzyme, and also plays a role in the binding of TIMP.
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PMID:Fragments of human fibroblast collagenase. Purification and characterization. 255 22

Matrix vesicles (MV) isolated from chicken growth plate by collagenase digestion and incubated in 45Ca-labelled synthetic cartilage lymph (SCL) rapidly induce mineral formation. 45Ca uptake occurs in three distinct stages: (1) an initial lag period of limited accumulation, (2) a period of rapid ion uptake and (3) an extended period of slower uptake. Treatment of MV with buffered aqueous 1,10-phenanthroline (OP), a metal ion chelator, eliminated the lag period, promoting immediate, enhanced Ca2+ uptake. Analysis of MV for trace metals showed them to contain relatively high concentrations of Zn (1.58 mumol/g MV) and lesser amounts of Cu (0.07 mumol/g MV). At least 30-40% of the Zn was readily extractable in isosmotic buffers. Addition of Zn to SCL at levels as low as 5 microM completely inhibited MV mineralization; addition of OP to Zn-inhibited MV restored their ability to mineralize. The findings suggest that Zn2+ ions act as an endogenous regulator of MV Ca2+ uptake and that the normal lag period results from a competition between Zn2+ and Ca2+ for high affinity Ca2+ binding sites in the MV membrane or within the MV lumen. Other metals tested included Cu2+, Pb2+ and Cd2+ which had little or no effect on MV mineralization, Mn2+, which had an intermediate effect, and Al3+, which was found to be almost as inhibitory as Zn2+. This finding may have implications for aluminum-associated osteomalacia.
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PMID:Regulatory effect of endogenous zinc and inhibitory action of toxic metal ions on calcium accumulation by matrix vesicles in vitro. 261 45

Collagenase has been purified from the culture medium of a human myometrial smooth muscle cell line, and the properties of the pure enzyme compared to those of collagenase from another human mesenchymal cell, the fibroblast. The smooth muscle collagenase was purified using a new, rapid, and convenient three-step purification procedure consisting of chromatography on iminodiacetate-agarose chelated with zinc and on Cibacron Blue-agarose followed by gel filtration on Ultrogel AcA-44. The resultant pure collagenase is secreted as a zymogen indistinguishable from that of the fibroblast enzyme in molecular weight, amino acid composition, and in the nature of its conversion to active enzyme by trypsin. The amino acid sequence of the two enzymes at the trypsin cleavage site is the same. The two collagenases are also indistinguishable immunologically and display essentially identical kinetic behavior on a variety of collagen substrates. Although the two collagenases appear to be identical proteins, the mechanisms which regulate their production appear to be very different. Glucocorticosteroids, which inhibit collagenase production in human skin fibroblasts are without effect in the uterine smooth muscle cell. In contrast, the smooth muscle cell appears to require a component present in fetal bovine serum in order to produce the enzyme.
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PMID:Purification and characterization of human myometrial smooth muscle collagenase. 283 76


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