Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tissue inhibitor of metalloproteinases (TIMP, M(r) 30,000) is secreted by many cell and tissue types and has been shown to inhibit most secreted mammalian metalloproteinases. In matrix and tissue invasion assays, the inactivation or removal of TIMP enhances invasiveness. However, many of the cells that secrete TIMP also secrete other metalloproteinase inhibitors. By analysis of medium conditioned by various endothelial, mesenchymal, and neural cells on SDS-.substrate-polyacrylamide-inhibitor gels (reverse zymograms), we have detected at least three other distinct inhibitors of metalloproteinases (IMPs). Some or all of these IMPs have been detected in secretions of mouse, rabbit, sheep, and human cells and are all smaller in apparent molecular size than TIMP (IMP-1, M(r) 26,000; IMP-2, M(r) 21,000; IMP-3, M(r) 18,000). These IMPs are not proteolytic degradation products of TIMP nor do they represent nonglycosylated TIMP. The IMPs do not cross-react in the native or denatured state with any of several anti-TIMP antibodies. The IMPs appear to be regulated independently of each other and of TIMP. In vitro, the complex consisting of one of the IMPs, or TIMP, and a metalloproteinase can be dissociated into functional inhibitor and metalloproteinase. Whether this characteristic is significant in vivo is not known. IMP-2 has been purified from several sources and shares sequence homology with TIMP, suggesting that the IMPs and TIMP may constitute a gene family. The most significant characteristic of IMP-2 is that it appears to preferentially inhibit, on a mole:mole basis, the M(r) 68,000 gelatinase rather than collagenase or stromelysin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secreted inhibitors of metalloproteinases (IMPs) that are distinct from TIMP. 148 40

An antiserum to rabbit bone stromelysin (proteoglycanase) was raised in sheep and characterized as specific, recognizing the enzyme from both different tissue sources and different species. This antiserum and a specific antiserum to rabbit bone collagenase were used in the study of metalloproteinase production by rabbit articular chondrocytes stimulated with either interleukin 1 or mononuclear cell-conditioned medium. It was shown by electroimmunoblotting that the apparently co-ordinate (mole:mole) induction of collagenase and stromelysin activity with time correlated in either case with an increase in enzyme protein. The stimulated production of both enzymes could be modified in parallel by a variety of compounds. Immunohistochemical studies confirmed that although most cells were producing both metalloproteinases simultaneously, some chondrocytes produced detectable levels of only one. The data are discussed in relation to the mechanisms of breakdown in connective tissues.
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PMID:Characterization of a specific antiserum to rabbit stromelysin and demonstration of the synthesis of collagenase and stromelysin by stimulated rabbit articular chondrocytes. 302 9

Promatrilysin expressed in Escherichia coli and Chinese hamster ovary cells contains 2.36 +/- 0.19 and 2.13 +/- 0.39 moles of zinc per mole of protein, respectively, while the activated enzyme contains 2.22 +/- 0.21. The catalytic domain of stromelysin-1 expressed in E. coli contains 2.22 +/- 0.11. Thus these matrix metalloproteinases contain two metal binding sites at which zinc is bound firmly and possibly a third site at which it is bound weakly. Promatrilysin and matrilysin do not contain significant amounts of Fe, Cu, Mn, or Ni. All known matrix metalloproteinases have a sequence homologous to the zinc binding site of astacin, HExxHxxGxxH, suggesting that one of the zinc sites is catalytic in agreement with the known inhibition of these enzymes by chelators.
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PMID:Zinc content of promatrilysin, matrilysin and the stromelysin catalytic domain. 800 31

Co-expression of several members of the matrix metalloproteinase (MMP) family is a characteristic of human carcinomas. To investigate the role of the recently cloned collagenase-3 (MMP-13) in epidermal tumors, we studied samples representing malignant (basal and squamous cell carcinoma, Paget's disease), pre-malignant (Bowen's disease, solar keratosis), and benign (keratoacanthoma, seborrheic keratosis, linear epidermal nevus) tumors. Basal cell carcinomas expressed collagenase-3 mRNA in focal areas of keratinized cells, the squamous differentiation of which was confirmed by positive immunostaining for involucrin. Apoptosis was observed in central parts of these foci. In squamous cell carcinomas, collagenase-3 expression was detected at the epithelial tumor front and less frequently in the surrounding stromal cells. Collagenase-3 mRNA co-localized with immunostaining for laminin-5, an adhesion molecule suggested to participate in the migration of tumor cells. The pre-malignant and benign tumors were mostly negative for collagenase-3. Stromelysin-1, a potential activator of latent collagenases, was frequently expressed by stromal cells surrounding the malignant tumors, and the two MMPs occasionally co-localized in keratotic foci. Our results demonstrate that in basal cell carcinomas, expression of collagenase-3 is associated with terminal differentiation of epithelial cells. Furthermore, the gene is activated during skin carcinogenesis, and we suggest a role for collagenase-3 in degradation of the extracellular matrix associated with malignant epithelial growth.
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PMID:Human collagenase-3 is expressed in malignant squamous epithelium of the skin. 924 12