Inhibition of bovine nasal cartilage degradation by selective matrix metalloproteinase inhibitors
| Autor: | Hans Werner Lahm, Pat Eyers, Brown Paul Anthony, Michael J. Broadhurst, L H Elliott, John M. Budd, Trevor J. Hallam, Urs Röthlisberger, David Bradshaw, Geoffrey Lawton, Amanda Whittle, J. S. Nixon, Maisie James, Hill Christopher Huw, Janet E. Merritt, Neera Borkakoti, William Henry Johnson, Balraj Krishnan Handa, K. M. K. Bottomley |
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| Rok vydání: | 1997 |
| Předmět: |
Matrix metalloproteinase inhibitor
Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Peptide Mapping Biochemistry Stromelysin 1 medicine Animals Humans Lectins C-Type Aggrecans Enzyme Inhibitors Molecular Biology Aggrecan Nasal Septum Aggrecanase Extracellular Matrix Proteins Chemistry Cartilage Metalloendopeptidases Interleukin Cell Biology musculoskeletal system Molecular biology medicine.anatomical_structure Chondroitin Sulfate Proteoglycans Matrix Metalloproteinase 9 embryonic structures Collagenase Cattle Proteoglycans Collagen Matrix Metalloproteinase 1 Interleukin-1 Research Article medicine.drug |
| Zdroj: | Biochemical Journal. 323:483-488 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj3230483 |
| Popis: | N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage cultured in the presence of recombinant human interleukin 1alpha revealed a predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the ARGSVIL-containing fragments has been attributed to the action of a putative proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported cleavage product; comparison of this sequence with the available partial sequence of bovine aggrecan indicates that this is the product of a cleavage occurring towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors inhibited aggrecan loss from bovine nasal explants incubated in the presence of recombinant human interleukin 1alpha. A strong correlation between inhibition of aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r=0.93) suggests a role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting aggrecan loss from the cartilage explants as they were in inhibiting stromelysin. There was little or no correlation between inhibition of aggrecan metabolism and inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1). Studies with collagenase inhibitors with a range of potencies showed a correlation between inhibition of collagenase activity and inhibition of collagen degradation in the cartilage explant assay. This indicates that in interleukin 1alpha-driven bovine nasal cartilage destruction, stromelysin (or a closely related enzyme) is involved in aggrecan metabolism, whereas collagenase is principally responsible for collagen degradation. [on SciFinder (R)] |
| Databáze: | OpenAIRE |
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