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)

It has traditionally been believed that only the human collagenases (matrix metalloproteinase-1, -8, and -13) are capable of initiating the degradation of collagens. Here, we show that human trypsin-2 is also capable of cleaving the triple helix of human cartilage collagen type II. We purified human trypsin-2 and tumor-associated trypsin inhibitor by affinity chromatography whereas collagen type II was purified from cartilage extracts using pepsin digestion and salt precipitation. Degradation of type II collagen and gelatin by trypsin-2 was demonstrated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, zymography, and mass spectrometry, and tumor-associated trypsin inhibitor specifically inhibited this degradation. Although human trypsin-2 efficiently digested type II collagen, bovine trypsin did not. Furthermore, immunohistochemical staining detected trypsin-2 in the fibroblast-like synovial lining and in stromal cells of human rheumatoid arthritis synovial membrane. These findings were confirmed by reverse transcriptase-polymerase chain reaction and nucleotide sequencing. Trypsin-2 alone and complexed with alpha(1)-proteinase inhibitor were also detected in the synovial fluid of affected joints by time-resolved immunofluorometric assay, suggesting that trypsin-2 is activated locally. These results are the first to assess the ability of human trypsin to cleave human type II collagen. Thus, trypsin-2 and its regulators should be further studied for use as markers of prognosis and disease activity in rheumatoid arthritis.
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PMID:Trypsin-2 degrades human type II collagen and is expressed and activated in mesenchymally transformed rheumatoid arthritis synovitis tissue. 1619 46

In normal soft tissues, collagen is degraded primarily by collagenases from the matrix metalloproteinase family. Yet, collagenase-like activity of tumor-associated isoforms of other enzymes might be involved in cancer invasion as well. In the present study, we systematically examined collagen degradation by non-sulfated isoforms of trypsins, which were proposed to possess such an activity. We found that non-sulfated trypsin-1, -2, and -3 were able to cleave non-helical and unfolded regions of collagen chains but not the intact triple helix, similar to sulfated trypsins produced by the pancreas. Trypsin-2 sulfation did not affect the cleavage rate either. An apparent triple helix cleavage by tumor-associated trypsin-2 reported earlier likely occurred after triple helix unfolding during sample denaturation for gel electrophoresis. Nevertheless, tumor-associated trypsins might be important for releasing collagen from fibers through telopeptide cleavage as well as for degrading unfolded collagen chains, e.g. after initial cleavage and destabilization of triple helices by collagenases.
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PMID:Collagen degradation by tumor-associated trypsins. 2354 62