Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro collagenolytic and proteoglycanasic activity from human fibrillated osteoarthritic cartilage was determined using labelled proteoglycans and type II collagen as substrates. In vitro, a glycosaminoglycan-peptide complex (GP-C Rumalon) induced a dose-dependent inhibition of both collagenolytic and proteoglycanasic activities while sodium salicylate and indomethacin had only a weak suppressive effect on proteoglycanase. Phospholipase A2 activity was unmodified by GP-C suggesting that the effect of the drug on degradative enzymes was unrelated to prostaglandin formation.
Clin Rheumatol 1990 Sep
PMID:Study of the effect of a glycosaminoglycan-peptide complex on the degradative enzyme activities in human osteoarthritic cartilage. 226 38

The effect of transforming growth factor-beta 1 (TGF-beta 1) on matrix gene expression has been investigated during the process of wound repair, where the formation of new connective tissue represents a critical step in restoring tissue integrity. Split-thickness excisional wounds in the pig were studied by in situ hybridization in order to obtain subjective findings on the activity and location of cells involved in matrix gene expression after the administration of recombinant TGF-beta 1. Data focus on the stimulatory role of this growth factor in granulation tissue formation, on the enhanced mRNA content of collagen types I and III, fibronectin, TGF-beta 1 itself, and on the reduction in stromelysin mRNA, suggesting that increased matrix formation measured after treatment with TGF-beta 1 is due to fibroplasia regulated by the abundance of mRNAs for several different structural, matrix proteins as well as inhibition of proteolytic phenomena elicited by metalloproteinases. These studies reveal elastin mRNA early in the repair process, and elastin mRNA expression is enhanced by administration of TGF-beta 1. Moreover, we show that TGF-beta 1 was auto-stimulating in wounds, accounting, at least in part, for the persistent effects of single doses of this multipotential cytokine.
Lab Invest 1990 Sep
PMID:Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin. I. Excisional wound model. 239 27

We have determined the nucleotide sequence of a collagenase mRNA from rabbit synovial cells from which the primary structure of the encoded protein was deduced. This proteinase is 51% homologous to the enzyme that activates it from the zymogen form, rabbit synovial cell activator/stromelysin. Rabbit collagenase and activator/stromelysin thus share comembership in a gene family that includes human skin collagenase; the human and rabbit metalloproteinase, activator/stromelysin; and an oncogene-induced proteinase from rat named transin. The mRNA sequence of collagenase enabled us to completely map the structure of its gene, which is 9.1 kilobases and is composed of 10 exons and 9 introns. This is the first report of the structure of a collagenase gene. We show that it has striking similarity to additional members of this metalloproteinase gene family, transin genes I and II of rat. We have further sequenced genomic DNA flanking the collagenase gene and have identified nucleic acid elements of possible importance in gene regulation.
Biochemistry 1987 Sep 22
PMID:A gene for rabbit synovial cell collagenase: member of a family of metalloproteinases that degrade the connective tissue matrix. 282 72

Neutral metalloproteinases degrade components of the extracellular matrix, including collagen types I-V, fibronectin, laminin and proteoglycan. However, their ability to degrade intact glomerular basement membrane (GBM) has not previously been investigated. Incubation of [3H]GBM (50,000 c.p.m.; pH 7.5; 24 h at 37 degrees C) with purified gelatinase or stromelysin (2 units) resulted in significant GBM degradation: gelatinase, 46 +/- 2.2; stromelysin, 59 +/- 5.8 (means +/- S.E.M.; percentage release of non-sedimentable radioactivity; n = 4). In contrast, 2 units of collagenase released only 5.6 +/- 0.52% (n = 3) of the [3H]GBM radioactivity compared with 2.0 +/- 0.15% (n = 7) released from [3H]GBM incubated alone. Sephadex G-200 gel chromatography of supernatants obtained from incubations of [3H]GBM with either gelatinase or stromelysin confirmed the ability of these enzymes to degrade GBM and revealed both high-(800,000) and relatively low-(less than 20,000) Mr degradation products for both enzymes. GBM degradation by gelatinase and stromelysin was dose-dependent (range 0.02-2.0 units), near maximal between pH 6.0 and 8.6, and was completely inhibited (greater than 95%) by 2 mM-o-phenanthroline. Collagenase (2 units) did not enhance the degradation of GBM by either gelatinase (0.02 or 0.2 unit) or stromelysin (0.02 or 0.2 unit). Our results indicate that metalloproteinase-mediated GBM degradation by neutrophils and glomeruli may be attributable to gelatinase (neutrophils) and/or stromelysin (glomeruli) and suggest an important role for these proteinases in glomerular pathophysiology.
Biochem J 1988 Sep 01
PMID:Degradation of glomerular basement membrane by purified mammalian metalloproteinases. 284 58

A third metalloendopeptidase activity, gelatinase, has been completely separated from the collagenase and proteoglycanase activities of rabbit bone culture medium. Although the proteinase could not be purified to homogeneity in large amounts, it was possible to obtain accurate molecular weight values and activity after electrophoresis on non-reduced SDS/polyacrylamide gels. The latent form had an Mr of 65 000 which could be activated with 4-aminophenylmercuric acetate, APMA, to a form of Mr 61 000; under reducing conditions the latent and active forms had Mr of 72 000 and 65 000, respectively. Trypsin was a very poor activator of the latent enzyme. Gelatinase degraded gelatins derived from the interstitial collagens and it also had low activity on native types IV and V collagen and on insoluble elastin. Gelatinase acted synergistically with collagenase in degrading insoluble interstitial collagen. The specific mammalian tissue inhibitor of metalloproteinases inhibited gelatinase by forming a stable inactive complex. Comparison of the properties of gelatinase with those of collagenase and proteoglycanase suggest that the three proteinases form a family which together are capable of degrading all the major macromolecules of connective tissue matrices.
Biochim Biophys Acta 1985 Sep 20
PMID:Purification and characterization of a bone metalloproteinase that degrades gelatin and types IV and V collagen. 299 41

Relaxin (Rlx) is shown in vitro to increase the release of plasminogen activator (PA) activity from granulosa cells obtained from 28-day-old rats after priming 48 h before with PMSG. Priming with PMSG was essential for the subsequent marked increase in PA by the addition of Rlx to these cells in vitro. Under the same conditions Rlx also increased the release of both total collagenase and total proteoglycanase activities but not of beta-glucuronidase activity. The total collagenase and proteoglycanase activities of control cells are made up of essentially equal amounts of their respective active and latent enzymes. Rlx stimulation increases the amounts of the respective active enzymes while the latent collagenase and proteoglycanase activities are unchanged or decreased, respectively. The enzyme beta-glucuronidase was not stimulated by Rlx and appears not to be involved in follicular proteoglycan degradation. Granulosa cells harvested from preantral follicles responded most to FSH by PA production whereas cells from antral follicles responded more to LH, reflecting the known changes in concentration of FSH and LH receptors on these cells. The release of PA is maximal by all four hormones studied (FSH, LH, prostaglandin E1, and Rlx) on granulosa cells harvested from rats 48 h after PMSG treatment and this suggests that the follicles at this time are a mixture of both preantral and antral stages. The PA response to FSH is lost by 60 h after PMSG at the same time that the response to prostaglandin E1 is maintained at the same level, whereas that to Rlx and LH, although still significantly higher than controls, were decreased. By 70 h after PMSG, postovulatory, the responses to all hormones studied were lost. Thus, the involvement of PA in ovarian connective tissue alterations appears to be greatest in the period of follicular antrum formation rather than just before ovulation. Rlx is one of a number of hormones involved in the sequence of events culminating in follicle connective tissue remodeling as shown by its action on the release of three intrafollicular enzymes.
Endocrinology 1984 Sep
PMID:Relaxin increases the release of plasminogen activator, collagenase, and proteoglycanase from rat granulosa cells in vitro. 608 81

Human articular chondrocytes in culture produced large amounts of specific mammalian collagenase, gelatinase and proteoglycanase when exposed to dialysed supernatant medium derived from cultured human blood mononuclear cells (mononuclear cell factor) or to conditioned medium, partially purified by fractionation with ammonium sulphate (60-90% fraction), from cultures of human synovial tissue (synovial factor). Human chondrocytes and synovial cells also released into culture medium an inhibitor of collagenase of apparent molecular weight about 30 000, which appeared to be similar to the tissue inhibitor of metalloproteinases synthesised by tissues in culture. The amounts of free collagenase inhibitor were reduced in culture media from chondrocytes or synovial cells exposed to mononuclear cell factor or synovial factor. While retinol inhibited the production of collagenase brought about by mononuclear cell factor or synovial factor, it restored the levels of inhibitor, which were reduced in the presence of mononuclear cell factor or synovial factor. Dexamethasone markedly reduced the production of collagenase by synovial cells, while only partially inhibiting factor-stimulated collagenase production by chondrocytes. Addition of puromycin as an inhibitor of protein synthesis reduced the amounts of both collagenase and inhibitor to control or undetectable levels.
Biochim Biophys Acta 1983 Sep 22
PMID:Effects of retinol and dexamethasone on cytokine-mediated control of metalloproteinases and their inhibitors by human articular chondrocytes and synovial cells in culture. 631 Dec 83

Pseudoxanthoma elasticum (PXE) is an inherited disease characterized by calcified degenerative changes of elastin in the skin, eye, and vasculature. Previous studies suggested the abnormal presence of a protease from PXE fibroblasts that degrades sulfated proteoglycans. This study describes the use of a radioassay to quantitate proteoglycan degradation by proteases from normal and PXE fibroblasts. PXE protease had optimal activity at pH 6.0. Inhibition of activity by 5 mM diisopropylfluorophosphate, 5 mM phenylmethylsulfonylfluoride, and 0.1 mM HgCl2 was reversed by 10 mM dithiothreitol. Iodoacetamide (1 mM) irreversibly inhibited activity. Carbobenzyloxy-phenylalanyl-alanyl (0.1 mM) and carbobenzyloxy-lysyl-diazomethyl ketone (10 microM) inhibited the proteoglycanase activity. These data suggest that the PXE proteolytic proteoglycanase activity is a cysteine protease. After blocking activity with 5 mM EDTA, addition of 10 mM Mg++, Mn++, Cu++, or Co++ had little effect (less than 10%) on restoring activity, 10 mM CaCl2 restored approximately 70% recovery of the activity, and 10 mM ZnCl2 stimulated the activity to 500% of the initial level. Similar normal fibroblast samples contained little zinc-dependent activity and a substantial amount of calcium-dependent activity. Thus the distinction between the divalent ion requirements for proteoglycan degradation suggests that the PXE fibroblasts may produce a different cysteine protease than do normal fibroblasts.
J Lab Clin Med 1983 Sep
PMID:Cysteine protease characteristics of the proteoglycanase activity from normal and pseudoxanthoma elasticum (PXE) fibroblasts. 635 May 11

We investigated whether stromelysin activity in the medium of canine articular cartilage explants is associated with proteoglycan degradation in these explants. Cartilage explants were treated with recombinant human interleukin 1 alpha (rh-IL-1 alpha), lipopolysaccharide, or canine monocyte-conditioned medium. Proteoglycan synthesis and degradation were measured. Metalloproteinase activity (inhibitable by tissue inhibitor of metalloproteinase 2) in the culture medium was measured by use of fluorimetry with a quenched fluorescent substrate. Western blots of the medium were probed with polyclonal antibodies to human stromelysin, collagenase, and gelatinase. Neither metalloproteinase activity nor proteoglycan degradation were inducible in canine cartilage explants treated with rh-IL-1 alpha. However, proteoglycan synthesis was significantly (P < 0.05) decreased by concentrations of 10 and 100 ng of rh-IL-1 alpha/ml. Metalloproteinase activity in the medium accompanied proteoglycan degradation of cartilage treated with lipopolysaccharide and monocyte-conditioned medium. The metalloproteinase released into the medium was identified as prostromelysin by results of western blotting.
Am J Vet Res 1995 Sep
PMID:Effects of stromelysin activity on proteoglycan degradation of canine articular cartilage explants. 748 6

Plasmin-mediated extracellular proteolysis has been implicated in the degradation of bone in normal and pathological conditions. Normal and malignant osteoblasts can produce both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have used the osteosarcoma cell line MG63 to address the question of whether the enhanced bone turnover in osteosarcomas is mediated by t-PA or by u-PAA and to study the effect of the cytokine interleukin-1 alpha (IL-1 alpha), known to influence bone degradation, on the plasminogen activator production and extracellular matrix degradation in malignant osteoblastic cells. Furthermore, the effect of IL-1 alpha on the synthesis of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was analyzed. u-PA production by MG63 was high (approximately 180 ng/10(6) cells/24 h). Also t-PA and PAI-1 production was observed. u-PA production was rapidly increased in MG63 by IL-1 alpha (10 ng/ml), whereas an effect on t-PA production was only found after a prolonged incubation and hardly any effect of IL-1 alpha on PAI-1 production was observed. mRNA analysis revealed similar effects. u-PA receptor (u-PAR) mRNA was detectable in MG63 cells and could be increased by IL-1 alpha after 24 h. In MG63, u-PA-mediated extracellular matrix degradation was detectable, and IL-1 alpha increased the u-PA-mediated matrix degradation (approximately 2-fold). Under control conditions in MG63, only MMP-2, TIMP-1, and TIMP-2 mRNA could be observed. After the addition of IL-1 alpha, a very rapid increase in MMP-1 and MMP-3 mRNA could be observed as well as a moderate increase in TIMP-1 mRNA. The presence of MMP-2 was demonstrated by gelatin zymography. These results show that IL-1 alpha can stimulate u-PA production and can regulate extracellular proteolytic activity mainly via u-PA induction in the MG63 osteosarcoma cell line. Furthermore, IL-1 alpha has a strong stimulating effect on the production of MMP-1 and MMP-3. These findings suggest that u-PA and possibly MMP-1 and MMP-3 play an important role in the process of bone turnover in osteosarcomas.
J Bone Miner Res 1995 Sep
PMID:Regulation of plasminogen activation, matrix metalloproteinases and urokinase-type plasminogen activator-mediated extracellular matrix degradation in human osteosarcoma cell line MG63 by interleukin-1 alpha. 750 10


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