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

---

Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GPA1734, an inhibitor of BM collagen biosynthesis, was investigated in the CAM model system for its effect on angiogenesis. Evaluation of angiogenesis was performed by placing a thin plastic coverslip inscribed with concentric circles on the CAM and counting the number of vessels intercepting the circles. The rate of BM collagen biosynthesis was monitored using [U-14C] proline incorporation into CAM proteins and determining the collagenase-digestible protein fraction. A marked depression in the vascular density was observed in the CAM area under a plastic disc containing GPA1734 as compared to control discs placed on the CAM about 1 cm apart from days 9 to 12 of incubation. A concomitant decrease in collagenous protein biosynthesis was observed in the area under the discs containing GPA1734 and [U-14C]proline as compared to control discs containing only the radiolabeled proline. The forementioned effects of GPA1734 on CAM were specific because no similar effects were observed with a closely related compound, 9,10-dihydroxy-7-methyl-benzo[b]quinolizinium bromide or with GPA1734 plus Fe++, which did not affect the rate of BM collagen biosynthesis. These results suggest that inhibitors of BM collagen biosynthesis prevent angiogenesis by interfering with the formation of an essential component of the vessel wall. The search for such inhibitors may be a new approach in the development of antiangiogenic agents.
...
PMID:Inhibition of basement membrane biosynthesis prevents angiogenesis. 245 Feb 2

The inhibitory effect of chloramphenicol (CAP) on the DNA repair synthesis were studied on a primary cell culture of fetal liver tissue of rats. The fetuses were taken out with the umbilical cords and the placenta: then, the fetal livers were injected with a balanced salt solution and Type I collagenase through the umbilical vein. At the same time, the blood of the fetal livers were drained through the umbilical artery. The cells were detached at 10 degrees C with a steel mesh. Chloramphenicol 1.6-403.8 mmol/L did not show significant increase in DNA repair synthesis. The unscheduled DNA synthesis (UDS) was active when the positive control 7,12-dimethylbenzanthrancene(DMBA) was added alone to the culture in autoradiographic assay, but it was inactive when DMBA was added together with CAP. Therefore, it may be assumed that CAP has an inhibitory effect on the DNA repair synthesis.
...
PMID:[Effect of chloramphenicol on DNA repair synthesis in fetal liver cells of rats]. 264 54

Vibrio alginolyticus produces an extracellular collagenase which requires specific induction by collagen or its high-molecular-weight fragments. Peptone also induces collagenase during the late exponential and early stationary growth phases. The peptone inducers have been shown to have a broad molecular weight range between 1,000 and 60,000. The peptone inducers supported slow growth of V. alginolyticus when supplied as the sole nitrogen source in minimal medium. Digestion of the peptone inducers with purified V. alginolyticus collagenase resulted in a decrease in their inducing ability, whereas digestion with trypsin or alpha-chymotrypsin did not. This indicated that induction by the inducers required the presence of collagenase-sensitive bonds. Prolonged digestion of the inducers with collagenase did not completely eliminate the inducing ability of the inducers. The peptone inducers acted as inhibitors of collagenase. A minimal medium induction system has been developed which involves resuspending cells at high density in a medium containing succinate, (NH(4))(2)SO(4), KH(2)PO(4), and the peptone inducer. Cells grown in minimal medium induce earlier than cells grown on peptone, Casamino Acids, or tryptone. Collagenase production was shown to occur for 30 to 60 min in the presence of rifampin at levels which completely inhibit the incorporation of [(3)H]uracil into trichloroacetic acid-precipitable material. Chloramphenicol completely and immediately abolished collagenase production, which together with labeling studies has confirmed that collagenase production involves de novo synthesis of the enzyme. Both glucose and Casamino Acids repressed collagenase production, although synthesis of the enzyme continued for 30 to 60 min after their addition. The repression of collagenase production by glucose and Casamino Acids was more severe than the inhibition of enzyme formation due to addition of rifampin.
...
PMID:Peptone induction and rifampin-insensitive collagenase production by Vibrio alginolyticus. 624 22

The glycoprotein cell-CAM 105 is a member of the carcinoembryonic-antigen-(CEA)-gene family, involved in cell-cell adhesion of rat hepatocytes and expressed on the cell surface as a long (L) and a short (S) isoform with slightly differing molecular masses and isoelectric points. The cDNA of the L-isoform has been isolated and sequenced, as confirmed by the preparation of specific anti-peptide sera [Lin, S.-H., Culic, O., Flanagan, D. & Hixson, D. C. (1991) Biochem. J. 278, 155-161]. Recently, two additional cDNAs have been sequenced, which possess identical deduced primary structures, including short intracellular domains 10 amino acids in length, which differ from the cytoplasmic domain of the L-isoform specifically in the last four C-terminal amino acids. Here, we report on the production of the polyclonal antiserum [anti-(peptide 2)] by immunization with a synthetic hexapeptide (GGSGSF) corresponding to the unique intracellular C-terminal domain of these short cell-CAM 105 cDNA isoforms. This antiserum was specific in ELISA, immunoblot and immunoprecipitation assays for a protein with the same biochemical properties as the S-isoform of cell-CAM 105 expressed in rat liver. In addition, CNBr peptide maps of the S-isoform and the protein immunoprecipitated with anti-(peptide 2) serum were identical. Together, these results provide strong evidence that anti-(peptide 2) serum is specific for the S-isoform of rat liver cell-CAM 105. In immunoblot analysis on liver plasma membrane extracts prepared without collagenase perfusion, at least seven high molecular-mass proteins were observed which showed strong reactivity with mAbs against extracellular epitopes and L-isoform-specific antibodies but no reactivity with anti-(peptide 2) serum. Like the L-isoform, these proteins are expressed on the cell surface and might represent structural variants of cell-CAM 105.
...
PMID:Anti-peptide sera against cell-CAM 105 determine high molecular-mass variants of the long isoform in rat hepatocytes. 770 45

Induction of stromelysin and collagenase mRNAs in response to phorbol myristate acetate (PMA) and autocrine factors (CAF) was compared in primary cultures of lapine synovial fibroblasts and an immortalized line of these cells known as HIG-82. In both cell types, message induction was quicker for CAF than for PMA. Appearance of both stromelysin and collagenase mRNAs occurred earlier in HIG-82 cells and, unlike primary cells, HIG-82 cells partially resisted inhibition by cycloheximide. To determine whether differences in AP-1 activity could account for these observations, the induction of c-fos and c-jun mRNAs was studied in conjunction with gel shift assays for AP-1 binding. Both inducers increased the abundance of c-fos mRNA, although the response was weaker in HIG-82 cells. However, the increase in c-jun mRNA was more marked in HIG-82 cells; furthermore, this increase was sustained for over 6 h. Gel shift assays confirmed that in both types of cells PMA and CAF increased AP-1 binding activity. In primary cells, this activity was sensitive to cycloheximide, but in HIG-82 cells, there was only partial sensitivity to cycloheximide. The gel shift analyses and data from experiments using an AP-1-CAT reporter construct revealed, in many cultures, constitutive AP-1 activity in the absence of stromelysin and collagenase expression, suggesting that AP-1 alone is insufficient for matrix metalloproteinase induction. Antisense oligonucleotides to c-fos and c-jun strongly inhibited the induction of stromelysin mRNA in primary cells treated with PMA, but was only weakly active against message induction in HIG-82 cells. In neither primary cells nor HIG-82 cells did antisense oligonucleotides strongly inhibit stromelysin induction in response to CAF. These data suggest there may exist an AP-1-independent route to message induction or that factors other than c-FOS and c-JUN may be used in certain circumstances. Western blot analyses detected no marked difference between HIG-82 cells and primary cells in their resting levels of c-FOS and c-JUN. Thus the differences reported here between HIG-82 cells and primary cells in their resting levels of c-FOS and c-JUN. Thus the differences reported here between HIG-82 cells and primary cells in the kinetics and cycloheximide sensitivity of MMP induction may reside in their abilities to modify posttranslationally the relevant transcription factors.
...
PMID:Effects of immortalization upon the induction of matrix metalloproteinases in rabbit synovial fibroblasts. 863 83

Interstitial collagenase is secreted by the osteoblast in response to bone-resorbing agents. Previously, we cloned the rat interstitial collagenase cDNA from UMR 106-01 rat osteoblastic osteosarcoma cells. We demonstrated that induction of collagenase by PTH, a powerful resorbing agent, in UMR 106-01 cells is in part transcriptional. In the present study we isolate and characterize the rat interstitial collagenase gene. The gene consists of 10 exons and spans approximately 12 kbp. The major transcriptional start site, determined by primer extension analysis and confirmed by RNase protection assay, is 25 nucleotides upstream of the translational start site. The previously isolated cDNA was missing the 5'-untranslated sequence in addition to 17 nucleotides of the signal sequence of the preproenzyme; therefore, we also present these data. Chloramphenicol acetyl transferase (CAT) analyses were performed on the 5'-upstream region of the gene. These data indicate that PTH appears to mediate its effect through an AP-1 consensus-binding sequence (-51). Footprint analysis demonstrates protein binding to this site. Site-specific mutagenesis markedly decreased protein binding, which correlated directly with a decrease in CAT activation by PTH. Supershift data indicate that cAMP response element binding protein (CREB) is binding to this AP-1 consensus sequence. In addition we demonstrate that PTH induces phosphorylation of CREB.
...
PMID:Parathyroid hormone induction of rat interstitial collagenase mRNA in osteosarcoma cells is mediated through an AP-1-binding site. 881 27

Fundic Gland Polyps (FGPs) are small sessile (2-5 mm), usually multiple polyps arising in the gastric, acid-secreting mucosa of disputed histogenesis. They have been described in a sporadic form, prevalently in middle aged females, or associated with familial adenomatosis coli-Gardner's syndrome. We performed an immunohistochemical study on 24 sporadic FGPs, using monoclonal antibodies (MAbs) against differentiation markers, class II MHC antigens (HLA-DR), oncofetal and proliferation antigens, aimed to characterize the antigenic profile of the polyps. A preliminary cytogenetic study on five polyps was also done, using an in situ culture method after collagenase treatment. Cytokeratins 8-18 (CAM 5.2 MAb) and 20 (IT-Ks 20.8 MAb), Epithelial Membrane Antigen (EMA) and Chromogranin A were normally expressed by FGPs. FGPs did not express HLA II DR. FGPs did not react with an anti-CEA MAb (F6), but they were frequently positive (22/24, 91.6%) with B72.3 MAb (reacting with the cancer-associated mucin epitope sialyl-Tn). The PC10 MAb (against PCNA or cyclin) showed enhanced expression in the deep glandular-cystic compartment of FGPs; the PCNA index of FGPs was significantly higher than in normal fundic mucosa. The cytogenetic study on the 5 cases analysed, revealed a normal karyotype. We have demonstrated that FGPs express in the paranuclear zone the sialyl-Tn epitope, a side-chain sugar normally masqued in adult gastric mucins, thus revealing an alteration in mucin synthesis; FGPs' higher proliferation index as compared with normal fundic mucosa supports the hypothesis of their hyperproliferative nature.
...
PMID:Sporadic fundic gland polyps: an immunohistochemical study of their antigenic profile. 889 16

In this report, we demonstrate that the AP-1 site and a distal promoter element regulate transcriptional induction of collagenase-1 during monocytic differentiation. Chloramphenicol acetyltransferase expression constructs containing regions of the human collagenase-1 promoter were stably or transiently transfected into U937 cells, and reporter activity was assessed at various times after the onset of phorbol 12-myristate 13-acetate (PMA)-mediated differentiation. Rapid and strong induction of promoter activity was lost in constructs with a mutant AP-1 element; however, at 16-96 h post-PMA, the mutant collagenase-1 promoter displayed AP-1 independent PMA-mediated transactivation. The AP-1 mutant constructs also showed delayed transcriptional activation in PMA-treated fibroblasts. Western and supershift analyses indicated that functional Jun and Fos proteins were present in nuclear extracts of PMA-differentiated U937 cells. Promoter deletion constructs demonstrated the potential role of distal promoter sequences in regulating collagenase-1 transcription. In particular, Western, supershift, and promoter deletion analyses suggested a role for CCAAT/enhancer-binding protein-beta (C/EBP-beta) binding site between -2010 and -1954 in regulating transcription of collagenase-1 in monocytic cells. Our findings suggest that distinct regulatory elements, acting somewhat independently of each other, control expression of collagenase-1. In addition, our data suggests that the rapid PMA-mediated induction of collagenase-1 transcription is controlled by a mechanism distinct from that regulating the sustained expression of this proteinase in activated macrophages.
...
PMID:Transcriptional induction of collagenase-1 in differentiated monocyte-like (U937) cells is regulated by AP-1 and an upstream C/EBP-beta site. 911 42

We have identified an IL-10 inducible enhancer (HTE) (5'-CACGATGACTCATCACTGTTGAAAGACA-3') (-864 to -836 bp) and associated silencer element (HTS) (5'-CCACTGGCCCATCGTATAT-3') (-1284 to -1266 bp) in the 5' promoter region of the human tissue inhibitor of metalloproteinase-1 (TIMP-1) gene. Chloramphenicol acetyl transferase (CAT), electrophoretic migration shift assays (EMSAs), and DNase footprinting revealed that IL-10 (15 ng/ml for 1-2 h) induced the HTE enhancer. In comparison, phorbol ester stimulated the HTS silencer and blocked IL-10's effects in a dose-dependent, orientation- and position-independent fashion, suggesting that HTS is a true silencer element. EMSAs combined with deletion and mutation analysis of the HTE and HTS elements confirmed these observations. Finally, Northern blot, Western blot, immunoprecipitation, and ELISA analysis showed that IL-10 (15 ng/ml) induced TIMP-1 expression (approximately 10-fold by 18 h), whereas PMA (100 ng/ml) inhibited the stimulatory effects of IL-10 on TIMP-1 expression. The data indicate that HTE and HTS function as positive and negative regulatory elements that control human TIMP-1 expression.
...
PMID:Identification of positive and negative regulator elements for the tissue inhibitor of metalloproteinase 1 gene. 977 93

Eosinophil and mast cell infiltrations are consistent findings in nasal polyp tissue. Previous studies have shown that matrix metalloproteinases (MMPs) may be involved in eosinophil infiltration in airway mucosa of asthmatic patients, and that transforming growth factor-beta1 (TGF-beta1) induces extracellular matrix deposition in nasal polyp tissue. The aim of this study was to evaluate the role of MMPs and tissue-inhibitor of metalloproteinase-1 (TIMP-1) in association with TGF-beta1, eosinophils and mast cell activation in nasal polyp tissue. Nasal polyp tissues from 20 patients who underwent polypectomies were collected and prepared into tissue homogenate. Eosinophil cationic protein (ECP) and tryptase levels were measured by CAP system (Pharmacia, Sweden). MMP-2, MMP-9, TIMP-1 and TGF-beta1 levels were measured by enzyme-liked immunosorbent assay. MMP-2 was the predominant form of MMPs, followed by MMP-9 and TIMP-1. There were significant correlations between ECP, and MMP-9, MMP-2, TGF-beta1 and tryptase, but not with TIMP-1. Significant correlations were noted between tryptase, and MMP-2, MMP-9, and TGF-beta1, but not with TIMP-1. Close correlations were noted between TGF-beta1, and MMP-9 and MMP-2, but not with TIMP-1. MMP-2, MMP-9, and TGF-beta1 may contribute to eosinophil and mast cell migrations into nasal polyp tissue.
...
PMID:Eosinophil inflammation of nasal polyp tissue: relationships with matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, and transforming growth factor-beta1. 1258 95


1 2 Next >>

---