Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intraperitoneal administration of [3H]thymidine to adult rats resulted in the rapid appearance of label in the adipocyte fraction of collagenase digests of adipose tissue. Low-speed centrifugation followed by freezing and slicing showed the label to be uniformly distributed in the adipocyte fraction. The presence of label in DNA was confirmed by hydrolysis with deoxyribonuclease and by inhibition of incorporation with hydroxyurea. Organelle fractionation revealed that the label was predominantly in nuclei, and radioautography showed that only a few adipocyte nuclei were labeled. The label in the adipocyte fraction could not be reduced by increased collagenase digestion or by trypsin treatment. Mixing of labeled adipocytes with unlabeled stroma did not result in decrease of label and addition of labeled stroma to unlabeled adipocytes did not cause significant transfer of radioactivity. Addition of [3H]thymidine to the collagenase digestion medium of unlabeled adipose tissue resulted in more incorporation by adipocytes than by stroma, suggesting the presence of a very rapidly proliferating cell type associated more with adipocytes than with stroma. In vivo turnover studies of labeled DNA indicated that there are two components in both adipocytes and stroma, a rapidly labeled component with a half-life of only several days and another with a half-life of several months. These experiments suggest that there is a rapidly proliferating cell type in adipose tissue, closely associated with mature adipocytes, that may be an adipocyte progenitor or may have some other unknown function.
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PMID:Isotopic labeling of DNA in rat adipose tissue: evidence for proliferating cells associated with mature adipocytes. 49 48

Rabbit proactivator is a neutral metalloproteinase that activates another metalloproteinase, procollagenase, and degrades noncollagenous matrix. We describe the construction of an activator complementary DNA (cDNA) clone, which is 1.9 kb, that selects a 2.1-kb messenger RNA (mRNA) in Northern blot hybridizations. Nucleic acid sequence studies of the activator cDNA indicate 1) that it encodes protein Mr 53,881, 2) that this protein exhibits approximately 80% homology with rat transin, an oncogene-induced protein with a previously unknown function, and 3) that, in the first 172 residues, it is virtually identical to the rabbit metalloproteinase, stromelysin. Homology between rabbit activator and human skin collagenase is approximately 50%. Activator and collagenase mRNA are coordinately regulated; untreated cultures of rabbit synovial fibroblasts produce low levels of each protein, but addition of phorbol myristate acetate (10(-8)M) results in an increase in mRNA for both proteins by 2.5-5 hours. Adding all-trans-retinoic acid (10(-6)M) or dexamethasone (10(-7)M) to phorbol-stimulated cells coordinately suppresses both activator and collagenase mRNA. Our data suggest the existence of coordinately regulated metalloproteinases that are important in the modulation of connective tissue metabolism.
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PMID:Cloning of a complementary DNA for rabbit proactivator. A metalloproteinase that activates synovial cell collagenase, shares homology with stromelysin and transin, and is coordinately regulated with collagenase. 282 26

We previously reported that follistatin-related protein (FRP)/TSC-36 was one of the target antigens of autoantibodies in rheumatoid arthritis (RA) and that the appearance of serum autoantibodies to FRP correlated to disease activity in RA. However, the significance of FRP in autoimmunity remained to be explained due to the unknown function of FRP. Here, we disclose in part the function of FRP. Transforming growth factor (TGF)-beta augmented FRP gene expression in synovial cells. FRP reduced synovial production of matrix metalloproteinase (MMP)-1, MMP-3 and prostaglandin E(2), potent agonists of joint destruction in RA. In contrast, autoantibodies to FRP from patients with RA increased their production by blocking FRP activity, probably in the autocrine system. Moreover, FRP down-regulated synovial expression of FOS (c-fos), which seemed responsible for the reduction in MMP-1 and MMP-3 caused by FRP. Therefore, FRP and its autoantibody can be regarded as defensive and offensive factors respectively in rheumatoid arthropathy. The major epitope of autoantibodies to FRP was mapped to the sequence LKFVEQNE (residues 169-176) and homologous sequences were found in proteins from Escherichia coli, Epstein-Barr virus, etc. FRP and its autoantibody may provide some clues to elucidate the process of disease development and a new approach to the design of therapeutics in RA.
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PMID:Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis. 1250 27

A Japanese flounder Paralichthys olivaceus cDNA microarray containing 871 unique cDNAs including 91 putative immune-related genes from our EST studies was constructed and used to characterize of gene expression of in vitro grown kidney cells stimulated with mitogens such as ConA, PMA, LPS or infected with hirame rhabdovirus (HRV). The numbers of genes whose expressions were increased or decreased by these factors were: 17 by Con A, 139 by PMA, 76 by LPS and 182 by HRV infection. The treatment of Con A for 1 and 6h affected the expression of only a few of the immune-related genes. PMA down-regulated far more genes than it up-regulated. Apoptosis-related factors, such as c-fos, NGF induced protein IB and NR13 genes, were among the genes whose expressions were induced by PMA. LPS induced the expression of inflammation-related genes, such as IL-1beta, monocyte chemotactic protein 1 and collagenase. The expressions of many genes were induced after 3h HRV infection but some of them were decreased to the basal level after 6h HRV infection. The expression of some genes of unknown function were induced or reduced by Con A, PMA or LPS or by HRV infection in different time periods. From all of the gene expression profiling in this study, we could get lots of information about the dynamic changes in the gene expression of the kidney cells under different stress or stimulations.
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PMID:Expression profiling of immune-related genes from Japanese flounder Paralichthys olivaceus kidney cells using cDNA microarrays. 1575 48

A previously generated collection of 11 Tn5-luxAB insertion mutants of Sinorhizobium meliloti harbouring lux reporter gene fusions induced under microaerobic (1% O2) conditions was further characterized and mapped on the sequenced S. meliloti genome. One highly induced gene fusion from this collection (loe-7) was found to be located in the intergenic region between sma1292, encoding a putative protease/collagenase, and a gene of unknown function (sma1294). The loe-7 fusion had been shown previously to be partially controlled by the oxygen sensor/regulator FixLJ system, but significant ( approximately 40%) Lux activity remained in a fixLJ mutant background. Therefore, a secondary Tn1721 mutagenesis of the loe-7 strain was carried out. Nine Tn1721 ('dark') insertions completely abolishing the Lux activity of the loe-7 fusion under microaerobic conditions were isolated. Surprisingly, five dark insertions mapped in denitrification genes [napA, napC, nirK--two insertions--and sma1245 encoding a NnrR-like transcriptional regulator controlling denitrification in response to nitric oxide (NO)]; Tn1721 insertions in the respiration genes fixG and fixP resulted in a reduced expression of the loe-7-lux fusion, and insertions in the regulatory genes fixJ and fixK1 resulted in low, but still detectable Lux activity. On the contrary, insertions in the norD or norQ genes resulted in constitutive Lux activity. In these mutant strains, NO would be expected to accumulate under microaerobic conditions. NO was found to be able to strongly induce the loe-7-luxAB fusion under microaerobic and aerobic conditions, but only in the presence of the functional nnrR-like gene (sma1245). These results suggest that NO, via the NnrR regulator, can serve as a signal molecule to induce the loe-7-luxAB fusion in concert with the FixLJ system.
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PMID:A highly conserved Sinorhizobium meliloti operon is induced microaerobically via the FixLJ system and by nitric oxide (NO) via NnrR. 1687 1