Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the association constants of tissue inhibitor of metalloproteinases (TIMP)-3 with various matrix metalloproteinases with those for TIMP-1 and TIMP-2 using a continuous assay. TIMP-3 behaved more like TIMP-2 than TIMP-1, showing rapid association with gelatinases A and B. Experiments with the N-terminal domain of gelatinase A, the isolated C-terminal domain, or an inactive progelatinase A mutant showed that the hemopexin domain of gelatinase A makes an important contribution to the interaction with TIMP-3. The exchange of portions of the gelatinase A hemopexin domain with that of stromelysin revealed that residues 568-631 of gelatinase A were required for rapid association with TIMP-3. The N-terminal domain of gelatinase B alone also showed slower association with TIMP-3, again implying significant C-domain interactions. The isolation of complexes between TIMP-3 and progelatinases A and B on gelatin-agarose demonstrated that TIMP-3 binds to both proenzymes. We analyzed the effect of various polyanions on the inhibitory activity of TIMP-3 in our soluble assay. The association rate was increased by dextran sulfate, heparin, and heparan sulfate, but not by dermatan sulfate or hyaluronic acid. Because TIMP-3 is sequestered in the extracellular matrix, the presence of certain heparan sulfate proteoglycans could enhance its inhibitory capacity.
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PMID:Human tissue inhibitor of metalloproteinases 3 interacts with both the N- and C-terminal domains of gelatinases A and B. Regulation by polyanions. 1019 61

The role of biochemical factors in the onset and natural history of rotator cuff disease is not fully understood, but it is generally recognised that they could induce tendon damage in association with mechanical and vascular factors. In this study, 5 biochemical parameters were analysed (total protein concentration, matrix metalloproteinase (MMP)-2 or gelatinase A, MMP-9 or gelatinase B, type I collagen telopeptides, hyaluronic acid) in the synovial fluid (SF) aspirated from the gleno-humeral joint of 29 patients undergoing surgical therapy for rotator cuff lesions. Four different groups of patients were identified according to the severity of the lesion: partial tear of the rotator cuff, full thickness tear involving <or-1 tendon, full thickness tear involving >1 tendon and cuff tear arthropathy (CTA). The total SF protein concentration progressively increased with loss of integrity of the rotator cuff, reaching the highest levels in CTA. The absolute enzymatic activity of gelatinases was greater in full thickness tears than in partial tears, while it decreased in CTA. Conversely, the ratio between gelatinases and total protein content reached the highest level in partial tears and then progressively decreased. Collagen I telopeptides were significantly increased in full thickness tears and CTA, whereas the levels of hyaluronic acid decreased with worsening of rotator cuff disease. These findings support the hypothesis that gelatinases, which are involved in physiological tendon remodelling, intervene in the evolution of rotator cuff disease, too. Increased levels of type I collagen telopeptides give evidence that tendon tears are associated with an anatomic loss of tendon tissue and not with simple tendon retraction.
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PMID:Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease. 1971 Nov 69

The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen. The MMP9-cleavable linker was introduced between PEG and the HA backbone to facilitate the detachment of the PEG corona from the conjugate at the tumor site. From the in vitro cellular uptake study, it was revealed that the conjugate was effectively taken up by the CD44-expressing TC-1 cancer cells in the presence of MMP9 via receptor-mediated endocytosis. When the conjugate was systemically administered into the tumor-bearing mice with endogenous OVA-specific CTLs, the tumor growth was markedly inhibited, which was attributed to the significant antigen presentation on the tumor cells. Overall, the MMP9-responsive conjugates bearing foreign antigens might have the potential as an alternative to CTL-based cancer immunotherapeutics.
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PMID:A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy. 2884 59