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)

First-trimester normal human trophoblast cells show some phenotypic similarities to malignant cells, e.g., rapid proliferation and ability to invade neighboring tissue, including basement membrane in situ, but do not have the ability for unlimited growth or metastasis. The present study examined whether the invasive ability of normal trophoblast cells is an intrinsic property of these cells, independent of the microenvironment provided by the pregnant uterus, and if so, whether they share some of the molecular mechanisms of invasion exercized by metastatic malignant cells. The ability of in vitro grown human trophoblast lines to invade an epithelium-free human amniotic membrane was measured from the temporal kinetics of retention of radioactivity within this membrane resulting from a penetration by 125I-iododeoxyuridine-labeled trophoblast cells. The magnitude of this invasion was compared to that of the highly metastatic human JAR-choriocarcinoma cell line and murine B16F10 melanoma line. Trophoblasts were found to share some of the same molecular mechanisms of invasion with the metastatic cell lines. Inhibitors of collagenase, plasmin, plasminogen, and plasminogen activators completely prevented invasion of the amnion by the trophoblast lines as well as by the metastatic JAR and B16F10 lines. Mersalyl, a compound known to activate collagenase, stimulated invasion by all cell lines tested, including under conditions in which plasmin activity was inhibited. In addition, trophoblasts produced significant levels of type IV collagenase and laminin, both of which appear to be important products of metastatic tumor cells required for basement membrane invasion. It may be concluded from these findings that the invasive property of first trimester human trophoblasts is genetically determined; that the magnitude of amnion invasion cannot differentiate between metastatic cell lines and invasive but nonmetastatic cell lines; and that invasiveness is not a sufficient prerequisite for metastatic ability.
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PMID:Normal nonmetastatic human trophoblast cells share in vitro invasive properties of malignant cells. 317 Jun 42

A small metalloproteinase that digests Azocoll was found in the uterus of the rat. Its activity increased to high levels during the postpartum period in parallel with the breakdown of the extracellular matrix exclusive of collagen (Sellers, A., and Woessner, J.F., Jr. (1980) Biochem. J. 189, 521-531). This enzyme has now been purified almost 7,000-fold to homogeneity from 12 g of tissue using molecular sieve chromatography, blue sepharose chromatography, and zinc-chelate chromatography. Gel electrophoresis with sodium dodecyl sulfate and dithiothreitol gives Mr = 28,000 for the latent form of the enzyme and Mr = 19,000 for the active form that arises spontaneously or by treatment with aminophenylmercuric acetate. The enzyme digests components of the extracellular matrix including gelatins of types I, III, IV, and V, fibronectin, and proteoglycan. It digests the alpha 2(I) chain of gelatin in preference to the alpha 1(I) chain and cleaves dinitrophenyl-Pro-Leu-Gly-Ile-Ala-Gly-Pro-D-Arg. It cleaves the B chain of insulin at two points: Ala14-Leu15 and Tyr16-Leu17. It has no action on collagens of types I, III, IV, or V at 26 degrees C and no action on elastin or phenylazo-Pro-Leu-Gly-Pro-D-Arg. The pH optimum is at pH 7 and the pI at 5.9. The enzyme requires zinc and calcium ions for activity; cobalt and strontium can partially replace these metal ions. The enzyme is not inhibited by low levels of phosphoramidon or Zincov. Its properties clearly distinguish it from collagenase, gelatinase (matrix metalloproteinase 2), and stromelysin (matrix metalloproteinase 3); it therefore constitutes a further member of the family of extracellular matrix metalloendopeptidases. The name matrix metalloproteinase 7 is proposed.
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PMID:Purification and properties of a small latent matrix metalloproteinase of the rat uterus. 318 22

Preterm delivery remains a preeminent problem in reproductive and pediatric care worldwide. Recent data suggest that cervicovaginal microflora and/or the inflammatory response they engender produce factors which can cause or predispose to preterm labor and rupture of membranes. Microorganisms mediating such processes may not be "recognized pathogens" and are often considered normal flora. These microorganisms may act singly, additively, or synergistically with host factors released during an induced inflammatory response. Quantitative, as well as qualitative aspects of cervicovaginal microflora may be important. Multiple cervicovaginal microorganisms produce IgA protease, neuraminidase, and mucinase which may facilitate passage of these and other agents past cervical barriers and into the lower uterine segment. Multiple microflora also produce phospholipases A2 and C, each of which can locally augment production of eicosanoids within the uterus which are important in cervical ripening and labor. Similar microflora produce various proteases, including collagenase, which can focally weaken the amniochorion and predispose to premature rupture of membranes and cervical ripening. Intrauterine microorganisms induce inflammatory reaction and may engender local release of similar proteases, phospholipases, as well as platelet-activating factor (PAF) and lymphokines which can also initiate or further potentiate labor-inducing mechanisms. Recognition of microbe-induced pathogenesis of some cases of preterm birth offers the hope of specific treatment and prophylaxis. In recent studies, administration of erythromycin and tocolytic agents was associated with an improved outcome in selected women with preterm labor. Further microbiological and clinical studies are ongoing. "Just why so many gravidas go into labor prematurely and hence give birth to infants who often are unable to cope with extrauterine conditions is one of the great unsolved problems of obstetrics."
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PMID:Prevention of preterm birth: new initiatives based on microbial-host interactions. 327 1

Preterm delivery remains the preeminent problem in perinatal care worldwide. Recent data suggest that cervical/vaginal microflora, and/or the inflammatory responses they engender, produce factors which can cause or predispose to preterm labor and rupture of membranes. Microorganisms mediating such processes may not be "recognized pathogens" and are often considered normal flora. These microorganisms may act singly, additively, or synergistically with host factors released during an induced inflammatory response. Both qualitative and quantitative aspects of cervical/vaginal microflora are likely important. Multiple cervical/vaginal microorganisms produce IgA proteases, neuraminidases, and mucinases which may facilitate passage of these and other agents past cervical barriers and into the lower uterine segment. Multiple microflora also produce phospholipases A2 and C, each of which can locally augment production of eicosanoids within the uterus which are important in cervical ripening and labor. Similar microflora produce various proteases, including collagenase, which can focally weaken the amniochorion and predispose to premature rupture of membranes and cervical ripening. Intrauterine microorganisms induce inflammatory reaction and may engender local release of similar proteases, phospholipases, oxygen radicals, as well as platelet activating factor (PAF), and lymphokines which can also initiate or further potentiate labor-inducing mechanisms. Roles for uteroplacental or systemic release of tumor necrosis factor (TNF) and various interferons are beginning to be understood. Recognition of microbe-induced pathogenesis of some cases of preterm birth offers the hope of specific treatment and prophylaxis. In recent studies, administration of erythromycin and tocolytic agents was associated with an improved outcome in selected women. "Just why so many gravidas go into labor prematurely and hence give birth to infants who often are unable to cope with extrauterine conditions is one of the great unsolved problems of obstetrics."
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PMID:Preterm birth and infection: pathogenic possibilities. 328 11

In an attempt to understand the mechanism by which estrogens stimulate cell proliferation and mammary carcinogenesis, metastatic human breast cancer cell lines (MCF7, ZR75-1) were found to secrete a 52,000 dalton (52K) protein under estrogen stimulation. Following its purification to homogeneity, the 52K protein was identified as a secreted procathepsin-D-like aspartyl protease bearing mannose-6-phosphate signals. This precursor displays an in vitro autocrine mitogenic activity on estrogen-deprived MCF7 cells and is able to degrade basement membrane and proteoglycans following its autoactivation. The total protease (52K + 48K and 34K) was detected and assayed by monoclonal antibodies and was found to be highly concentrated in proliferative and cystic mastopathies. In breast cancer, its cytosolic concentration appears to be correlated more to tumor invasiveness than to hormone responsiveness. The mRNA of the 52K protease accumulates rapidly following estradiol treatment, as was shown by Northern blot analysis with cloned cDNA. The 52K cathepsin-D-like protease is the first example of a lysosomal protease induced by estrogens in cancer cells. Results obtained using different approaches suggest that two cysteinyl cathepsins are also related to cell transformation and invasiveness. It has been proposed that cathepsin-B is involved in breast cancer and metastatic melanoma, and its regulation by estrogen has been shown in the rat uterus. Cathepsin-L corresponds to the major excreted protein (MEP) whose synthesis and secretion are markedly increased by transformation of NIH 3T3 cells with Ki ras and are regulated by several growth factors. In addition to secreted autocrine growth factors and to other proteases (plasminogen activator, collagenase), lysosomal cathepsins may therefore play an important role in the process of tumor growth and invasion as long as their precursor is secreted abundantly.
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PMID:Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? 331 45

The localization of collagenolytic activity within the tissue compartments of the mouse uterus was investigated during postpartum involution. The rate of collagenase activity was measured by analysis of tissue levels of hydroxyproline from the day of parturition to the 10th postpartum day. Collagen bonding was analyzed by viewing birefringence induced by the picrosirius red-binding technique. An attempt was made to interrelate quantitative analysis with the histologic distribution of collagen during postpartum days 1-10. Histologic and quantitative evidence indicated the following: 1) The collagenous compartments of the endometrium and myometrium differ in their response to the postpartum rise in collagenase activity; collagen degradation occurs primarily in the endometrium, that is, the myometrial collagen remains, but much of the endometrial collagen is removed. 2) Endometrial collagen is degraded particularly in the immediate subluminal compartment.
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PMID:Removal of collagen bundles in murine uterus during postpartum involution. 335 57

A cDNA library, prepared from mRNA isolated from the uteri of 3-day estradiol-stimulated immature rats, was constructed in pBR322. From this library an estrogen-regulated clone, pERU3, was isolated. This clone contained sequences complementary to uterine mRNA that migrated during gel electrophoresis as a double band of about 5.0 and 5.8 kilobases. Little of this mRNA was seen in several other tissues examined. An increase in the amount of this RNA in uterus was seen 2 h after estradiol treatment, with maximum hybridization occurring, in different experiments, between 18 and 36 h, followed by a decline. Hybridization of the cDNA insert of the pERU3 plasmid with known probes indicated that it coded for alpha 1(I)-procollagen. This conclusion was supported by in vitro translation experiments in which the hybrid-selected mRNA complementary to pERU3 DNA was shown to code for a collagenase-sensitive protein with a size corresponding to that of alpha 1(I)-procollagen. This system, therefore, provides an additional tool for the study of the estrogen regulation of gene expression in the uterus.
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PMID:Estrogen regulation of alpha 1(I)-procollagen messenger ribonucleic acid in the rat uterus. 383 55

Foetal-bovine nuchal ligament and aorta, together with adult-bovine aorta and pregnant uterus, were extracted under dissociative conditions in the absence and in the presence of a reducing agent. A collagenous glycoprotein of Mr 140000 [designated component 140K(VI)], identified in these extracts as the major periodate/Schiff-positive component, was shown to be related to collagen type VI. Digestion of non-reduced extracts with pepsin yielded periodate/Schiff-positive peptides that, on the basis of their electrophoretic mobilities, amino acid analyses and peptide 'maps', were identical with type VI collagen fragments prepared by standard procedures. It is concluded that collagen type VI occurs in vivo as molecule comprising three chains of Mr 140000 in which the helical domains account for about one-third of each polypeptide. Biosynthetic experiments with nuchal-ligament fibroblasts in culture demonstrated that a bacterial-collagenase-sensitive [3H]fucose-labelled glycoprotein, Mr 140000, was immunoprecipitated from culture medium by a specific antibody to the pepsin-derived form of collagen type VI. This result suggests that the collagenous polypeptides [140K(VI) components] represent the biosynthetic precursors of type VI collagen that do not undergo processing to smaller species before deposition in the extracellular matrix. Analyses of 5M-guanidinium chloride extracts of tissues with markedly different elastin contents and at different stages of development suggested that there was no relationship between collagen type VI and elastic-fibre microfibrils, a conclusion supported by the observation that the immunoprecipitated glycoprotein, Mr 140000, was distinct from the glycoprotein MFPI, Mr 150000, believed to be a constituent of these microfibrils [Sear, Grant & Jackson (1981) Biochem. J. 194, 587-598].
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PMID:Isolation from bovine elastic tissues of collagen type VI and characterization of its form in vivo. 393 35

1. The earlier observation (Woessner, 1969) of oestradiol inhibition of collagen breakdown is confirmed and extended. Administration of 100mug of oestradiol-17beta/day to parturient rats strongly inhibits the loss of collagen from the involuting uterus. Three experiments show that this effect is due to an inhibition of collagen degradation rather than to a stimulation of collagen synthesis. 2. Uterine collagen was labelled with hydroxy[(14)C]-proline by the administration of [(14)C]proline near the end of pregnancy. By 3 days post partum, control uteri lost 83% of their collagen and 90% of their hydroxy[(14)C]proline. Uteri from oestradiol-treated rats lost only 50% of both total and labelled hydroxyproline, with no decrease in the specific radioactivity of the hydroxyproline. 3. Incorporation of [(14)C]proline into uterine collagen hydroxyproline in vivo was not affected by oestradiol treatment. 4. Urinary excretion of hydroxyproline was increased in post-partum control rats and decreased in oestradiol-treated rats. 5. An enzyme capable of cleaving 4-phenylazobenzyloxycarbonyl-l-prolyl-l-leucylglycyl- l-prolyl-d-arginine (a substrate for clostridial collagenase) increased in activity in the post-partum uterus and was unaffected by oestradiol treatment. 6. Uterine homogenates digested uterine collagen extensively at pH3.2. This digestion was unaffected by the oestradiol treatment. 7. Lysosomal fractions prepared by density-gradient centrifugation of uterine homogenates contained coincident peaks of cathepsin D activity and peptide-bound hydroxyproline. The cathepsin D and hydroxyproline contents of this peak were unaffected by oestradiol treatment.
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PMID:Oestradiol inhibits collagen breakdown in the involuting rat uterus. 465 Nov 36

Well characterized monospecific antisera against pepsin-extracted bovine type VI collagen were used to identify and characterize the intact form of type VI collagen. In immunoblotting experiments the antisera reacted with the pepsin-resistant fragments of the alpha 1(VI) and alpha 3(VI) chains, but not with the fragment of the alpha 2(VI) chain. Extracts obtained from uterus and aorta with 6 M guanidine HCl contained two immunoreactive polypeptides of Mr = 190,000 and 180,000 based on globular protein standards. Cleavage of extracts with pepsin generated the previously characterized pepsin-resistant fragments of alpha 1(VI) and alpha 3(VI), indicating that the higher molecular weight polypeptides represent the intact parent chains, alpha 1(VI) and alpha 3(VI). Digestion of extracts with bacterial collagenase released an Mr = 100,000 noncollagenous fragment from the alpha 1(VI) chain. Thus, intact type VI collagen in tissues contains a relatively short triple helical domain and at least one very large globular domain which is sensitive to pepsin but resistant to collagenase digestion. Immunoblotting revealed a polypeptide of Mr = 240,000, which we suggest represents the pro-alpha 1(VI) chain, in the culture medium of bovine fibroblasts. Bands intermediate in molecular weight between 240,000 and 190,000 were identified in cell layers. These findings establish type VI collagen as a protein with very large nontriple helical domains, a property that undoubtedly plays an important role in its function.
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PMID:Characterization of the precursor form of type VI collagen. 620 13


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