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)

The correlation between activation of macrophages and increased secretion of plasminogen activator suggests that macrophages are exposed to the protease plasmin. Incubation of 125I-labeled, caseinate-elicited guinea pig peritoneal macrophages with plasmin cleaves a surface protein, gp160, characterized previously by its sensitivity to trypsin. The gp160 fragments produced by plasmin (fr85 and fr71), which remain disulfide-bonded in the membrane, comigrate with the fragments produced by trypsin, indicating close or identical cleavage sites. No other detectable 125I-labeled surface component is cleaved by plasmin. Neither gp160 nor any other detectable 125I-labeled surface component was cleaved by a series of other proteases associated with inflammation including thrombin, collagenase, pancreatic elastase, leukocyte elastase, cathepsin G, and urokinase. Analysis with the use of homogeneous plasmin from guinea pig plasma shows that concentrations as low as 50 micrograms/ml cause measurable cleavage of gp160 in 30 min.
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PMID:Macrophage surface component gp160: sensitivity to plasmin and other proteases. 646 Aug 5

Activation of bovine plasma prekallikrein was investigated with several proteinases. Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC 3.4.21.8] by bovine activated Hageman factor, trypsin [EC 3.4.21.4] and Pronase P (proteinases from Streptomyces griseus) and more gradually by papain [EC 3.4.22.2] and ficin [EC 3.4.22.3]. Activation of prekallikrein was also observed with bovine plasmin [EC 3.4.21.7], but not with bovine clotting factors Xa (Stuart factor) [EC 3.4.21.6] and IXa (Christmas factor) or thrombin [EC 3.4.21.5]. Urokinase [EC 3.4.99.26], Reptilase, collagenase [EC 3.4.24.3], elastase [EC 3.4.21.11], alpha-chymotrypsin [EC 3.4.21.1], Nagarse [EC 3.4.21.14], and stem bromelain [EC 3.4.22 4] did not convert prekallikrein to kallikrein. Plasma kallikrein activated to Hageman factor released kinin rapidly from bovine high molecular weight (HMW) kininogen. However, from bovine low molecular weight (LMW) kininogen, liberation of kinin was extremely slow. The kallikrein activity was inhibited by soybean trypsin inhibitor (SBTI), Trasylol, diisopropylfluorophosphate (DFP), and N-alpha-tosyl-L-lysine chloromethylketone (TLCK), but not by egg-white trypsin inhibitor (EWTI), lima bean trypsin inhibitor (LBTI), heparin or hexadimethrine bromide (Polybrene). The kallikrein formed an enzyme-inhibitor complex with SBTI and Trasylol, but not with LBTI. Prekallikrein did not react with SBTI. Prekallikrein consists of a single polypeptide chain of molecular weight about 90,000, as estimated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Activation of prekallikrein by Hageman factor was found to involve cleavage of the single peptide bond on the disulfide-bridged polypeptide chain, and no change of molecular weight was observed during the activation. The peptide bond cleaved in prekallikrein by the activation was an Arg-X peptide bond on a disulfide-bridged polypeptide chain.
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PMID:Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor. 676 24

The virulence of Pseudomonas aeruginosa, which is easily differentiated from the two other most common pseudomonad pathogens, is low. This species primarily causes disease in patients with local anatomic changes or in the immune compromized hosts. A number of bacterial factors are involved in the pathogenesis of the microbe. Surface structures like the glycocalyx-capsular material-is involved in attachment to mucosal surfaces and resistance against phagocytosis and immunolysis of cells. The interference with bacterial components on mucociliar clearance of the bronchial tract have been described. In cystic fibrosis local environmental substances enhancing the production of capsular material have been described and the tendency for colonization of mucoid strains in cystic fibrosis probably is related to these factors. Another general component of gram-negative bacteria is endotoxin, but the toxicity of this cell wall constituent is relatively low in P. aeruginosa. A number of proteolytic enzymes with a probable role in disease have been described: collagenase, fibrinolysin, elastase, caseinase, and gelatinase. A proteolytic enzyme with activity against substances like casein, egg albumin, gluten, and haemoglobin has been described. A component like exotoxin A can produce skin lesions and antibodies produced with toxoid of exotoxin A are protective against this bacterial agent. Enterotoxin has been described based on rabbit intestinal loop preparations, but has not been further characterized and diarrhoea is rarely caused by P. aeruginosa. Haemolytic effect has been caused by a heat labile phospholipase C and by a heat stabile moiety. A leucocidin has been described: this may in part be capsular material. In addition, an exoenzyme S has been suggested as a virulence factor.
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PMID:Pathogenetic factors of Pseudomonas aeruginosa. 679 59

Culture-produced subendothelium (SE) has been prepared from cultured porcine aortic endothelial cells (ECs) by a rapid freeze-thaw, ice-shearing method. En face preparations of this in situ SE material are essentially free of intact or damaged cells and cell debris and consisted of an extensive meshwork of microfibrillar and amorphous material. Washed porcine platelets reacted extensively with this SE material and were associated with the SE as single adherent platelets, single spread platelets, and varying-sized platelet aggregates or 'microthrombi'. Platelet aggregates were associated only with the damaged or frayed edges of the SE, and the platelets had undergone extensive SE-induced contraction and degranulation, as indicated by transmission electron microscopy. Platelet-SE interaction was affected by pH, calcium, platelet concentration, rapid shaking and exposure time. Platelet-SE interaction was significantly enhanced by the addition of 0.1-1% citrated plasma or purified porcine F.VIIIR:WF. Pretreatment of the SE with thrombin, elastase, neuraminidase or hyaluronidase had no effect on platelet-SE interaction, whereas pretreatment with pepsin, plasmin, trypsin, alpha-chymotrypsin or collagenase decreased or completely abolished all platelet-SE interaction. Extraction of the SE with various solutions (high salt, detergents, etc.) had no effect on platelet-SE interaction, only solutions containing sodium dodecyl sulfate completely abolished all platelet-SE interaction.
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PMID:Culture-produced subendothelium. I. Platelet interaction and properties. 680 25

We have investigated the ability of neutral and lysosomal enzymes of mouse macrophages to degrade the insoluble extracellular matrices secreted by smooth muscle cells, endothelial cells, and fibroblasts. Matrices produced by smooth muscle cells contained glycoproteins, elastin, and collagens, but matrices of endothelial cells and fibroblasts contained no elastin. Sequential enzyme digestion of residual matrix revealed that plasmin, a product of macrophage plasminogen activation, degraded 50-70% of the glycoprotein in the matrices but did not degrade the elastin or the collagens. Purified macrophage elastase degraded glycoprotein and elastin components but had no effect on the collagens. The rate of elastin degradation by macrophage elastase was decreased in the presence of the glycoproteins. In contrast, human granulocyte elastase effectively degraded the matrix glycoproteins, elastin, and, to a lesser extent, collagens, Mammalian collagenase degraded only collagens. Conditioned medium from resident and inflammatory macrophages, containing mixtures of the secreted proteinases, degraded the glycoprotein and elastin components of the matrices. However, conditioned medium was less effective in degrading matrix than comparable amounts of purified macrophage elastase because > 90% of the elastase in the medium was in a latent form. Inclusion of plasminogen in the assays accelerated degradation. In the presence of plasminogen, glycoproteins were degraded readily by medium from P388D1, pyran copolymer-, thioglycollate-, and periodate-elicited macrophages and, to a lesser extent, by medium from endotoxin-elicited and resident macrophages; medium from P388D1, thioglycollate-, and periodate-elicited macrophages was most effective in elastin degradation, and resident, endotoxin-elicited and pyran copolymer-elicited macrophages degraded almost no elastin. The macrophage cathepsins D and B degraded all the matrix components at an optimum pH of 5.5 and acted with the secreted neutral proteinases to degrade the connective tissue macromolecules to amino acids and oligopeptides. These data indicate that macrophages at inflammatory sites contain and secrete proteolytic enzymes that could degrade the extracellular matrix.
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PMID:Degradation of connective tissue matrices by macrophages. I. Proteolysis of elastin, glycoproteins, and collagen by proteinases isolated from macrophages. 700 Sep 66

A rapid breakdown of collagen was found in granulation tissue induced by carrageenin in rats; the half-life of collagen in both growing and resorbing tissues was about 3.5 days, whereas that in non-resorbing tissue was about 7 days. On the other hand, the half-life of noncollagen protein in the growing, resorbing and non-resorbing tissues was about 2-3 days. epsilon-Amino-n-caproic acid n-hexyl ester, an inhibitor of plasmin and trypsin, selectively inhibited collagen breakdown in vivo without affecting the degradation of noncollagen protein or the syntheses of collagen and noncollagen protein in granulation tissues. A similar selective inhibition of collagen breakdown was also found upon treatment with soybean trypsin inhibitor. Collagenase activity was assayed directly in the insoluble 6,000 X g pellet of granulation tissue homogenates. epsilon-Amino-n-caproic acid n-hexyl ester and soybean trypsin inhibitor markedly inhibited the collagen breakdown in granulation tissue pellets in vitro. The results are consistent with those from in vivo experiments and suggest that both the inhibitors indirectly inhibit the collagen breakdown in granulation tissue through the inhibition of a latent collagenase-activating proteinase(s), because none of the inhibitors directly inhibit collagenase. It may be argued, therefore, that a proteinase(s) which activates a latent collagenase plays an important role in the rapid breakdown of collagen in granulation tissues.
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PMID:Selective inhibition of collagen breakdown by proteinase inhibitors in granulation tissue in rats. 725 73

Ovulation, recurring every midcycle of the mammalian female and triggered by a surge of luteinizing hormone (LH) released from the pituitary, is an essential prerequisite for fertilization and subsequent embryonic development. Here we shall describe two of the biological components of the ovulatory response, cumulus expansion (frequently denoted as cumulus maturation) and the rupture of follicular wall, both crucial for the release of a fertilizable ovum. The role of a proteolytic cascade and its regulation by eicosanoids will be emphasized in relation to follicle rupture. The new data implicating cumulus maturation as an essential step for the release of the ovum and the apparent mediatory role of interleukin-1 in this process will be presented. LH/hCG stimulates, in the preovulatory follicles, a cascade of proteolytic enzymes, including plasminogen activator (PA), plasmin and matrix metalloproteinase 1 (MMP-1). These enzymes bring about the degradation of perifollicular matrix and, most notably, the decomposition of the meshwork of collagen fibers which provides the strength to follicular wall. Furthermore, pharmacological blockage of any of these enzymes resulted in inhibition of follicle rupture. LH/hCG stimulates, in addition, an increase in ovarian production of eicosanoids. These include prostaglandins, obtained from arachidonic acid via the cyclooxygenase pathway and leukotrienes, the products of lipoxygenase. Previous studies from our and other laboratories have demonstrated the ability of inhibitors of cyclooxygenase and of lipoxygenases to suppress ovulation in several mammalian species. MK-886, which inhibits the translocation of 5-lipoxygenase (5-LO) from the cytosol and its binding to the membranal 5-LO activating enzyme, suppressed dose-dependently follicular rupture from the treated ovary. Zymographic analysis of ovarian extracts from PMSG/hCG-stimulated rats revealed a band of collagenolytic activity at 52kD, corresponding to human MMP-1 and at 72kD, corresponding to human MMP-2. Both activities were markedly stimulated by administration of hCG and were significantly inhibited by indomethacin, NDGA or MK-886. Thus, eicosanoids seem to mediate LH stimulation of follicular collagenase. Interleukin-1 (IL-1) has been recently implicated in ovulation. The ability of an IL-1 receptor antagonist (ra) to block ovulation in vivo and in vitro has been demonstrated recently. Morphological examination of the ovulatory follicles failing to ovulate suggests that this effect is exerted by inhibiting cumulus oophorus expansion and detachment from mural granulosa cells. In vitro, IL-1ra attenuated the action of hCG and FSH on cumulus expansion and follicular hyaluronic acid synthesis. Thus, IL-1 seems to mediate and/or facilitate gonadotropin action on cumulus expansion, and hence on ovulation.
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PMID:Ovulation as a tissue remodelling process. Proteolysis and cumulus expansion. 748 19

Dental plaque is the major aetiological factor in periodontal diseases and contains several proteolytic enzymes. The origin of these proteinases is, however, poorly studied. This study was undertaken to characterize collagenase present in dental plaque of adult periodontitis patients. Vertebrate-type rather than bacterial-derived collagenase activity was detected in extracts of both supra- and subgingival dental plaque extracts of adult periodontitis patients. Dental plaque collagenase was found to exist predominantly in autoactive form. Dental plaque collagenase from periodontally healthy individuals existed in latent from. Latent dental plaque collagenase from periodontitis lesions could be activated by a 95 kD chymotrypsin-like proteinase from Treponema denticola and human leukocyte cathepsin G but not by human plasmin. Incubation of purified latent leukocyte collagenase with whole cells of Fusobacterium nucleatum, Eubacterium saburreum, Prevotella buccae and Porphyromonas gingivalis, however, did not result to the activation of the enzyme. Doxycycline in vitro inhibited dental plaque collagenase with an IC50-value of 20 microM. Dental plaque collagenase degraded more efficiently type I and II collagens than type III collagen. Western-blot analysis with specific anti-human neutrophil collagenase-antibody revealed that both in supra- and subgingival dental plaque extracts dental plaque collagenase had undergone proteolytic conversion from an 80 kD proform to a 58 kD active form which is associated with catalytic autoactivity as measured by functional collagenase assay. This reflects proteolytic activation of leukocyte collagenase in dental plaque probably by other proteases derived from potent periodontopathogenic bacteria such as T. denticola or other PMN proteases such as cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular source, activation and inhibition of dental plaque collagenase. 759 2

We investigated the effect of gonadotropins on protease that were suggested to be implicated in the invasive activity of the trophoblast. hCG levels ranging from 10 x 10(3) to 333 x 10(3) IU/L produced a dose-dependent inhibition of the in vitro globinolytic activity of the purified proteases trypsin, chymotrypsin, and urokinase, but failed to inhibit plasmin, collagenase, elastase, and tissue-type plasminogen activator. Likewise, FSH inhibited purified trypsin and urokinase, but not plasmin or tissue-type plasminogen activator. Culture medium conditioned with human trophoblast displayed serine protease and urokinase-like activities; exposure of the cultured trophoblast to exogenous hCG markedly suppressed serine protease and urokinase activities in the conditioned medium. A short treatment of the conditioned medium with trypsin abolished the hCG-mediated inhibition of urokinase activity. The present findings offer an explanation for earlier observations that hCG reduced collagenase activity in trophoblasts without affecting the level of collagenase-specific mRNA. The present results are also consistent with the concept that hCG, by its direct ability to inhibit certain serine proteases and urokinase in trophoblast, suppresses a protease-mediated conversion of procollagenase to active collagenase. The ability of hCG to prevent initiation of the collagenolytic cascade suggests that gonadotropins may regulate the transient invasive activity of the trophoblast.
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PMID:Gonadotropin-mediated inhibition of proteolytic enzymes produced by human trophoblast in culture. 768 89

Proteolytic enzymes such as urokinase-type plasminogen activator (uPA), plasmin, and collagenase mediate proteolysis by a variety of tumor cells. uPA secreted by tumor cells can be bound to a cell surface receptor via a growth factor-like domain within the amino-terminal fragment (ATF) of the uPA molecule with high affinity. Urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and the tumor cell-surface receptor-bound plasmin and subsequently reduces tumor cell invasion and the formation of metastasis. The anti-invasive effect is dependent on the anti-plasmin activity of the UTI molecule, domain II in particular. We synthesized a conjugate between ATF of human uPA and a native UTI molecule or domain II of UTI (HI-8). The effect of the conjugates (ATF.UTI or ATF.HI-8) on tumor cell invasion in vitro was investigated. ATF.UTI and ATF.HI-8 bound to U937 cells in a rapid, saturable, dose-dependent, and reversible manner. A large part of receptor-bound ATF-UTI and ATF.HI-8 remains on the cell surface for at least 5 h at 37 degrees C. Inhibition of tumor cell-surface receptor-bound plasmin by ATF.UTI and ATF.HI-8 was markedly enhanced when compared with tumor cells treated either with ATF, UTI, or HI-8. Results of a cell invasion assay showed that ATF.UTI and ATF.HI-8 is very effective at targeting HI-8 specifically to uPA receptor-expressing tumor cells, whereas tumor cells devoid of uPA receptor may be less affected by the conjugates. Our results indicate that cell surface uPA and plasmin activity is essential to the invasive process and that the conjugates exhibit plasmin inhibition to the close environment of the cell surface and subsequently inhibit the tumor cell invasion through Matrigel in an in vitro invasion assay.
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PMID:Inhibitory effect of a conjugate between human urokinase and urinary trypsin inhibitor on tumor cell invasion in vitro. 771 45


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