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 have investigated the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in colorectal cancer by the immunostaining (avidin-biotin peroxidase complex method) and in situ hybridization (ISH). Both MMP-9 enzyme and messenger RNA (mRNA) for MMP-9 were located in tumor cells, neutrophils, monocyte-macrophages and fibroblasts in colorectal cancer tissue. The location of TIMP-1 mRNA was similar to that of MMP-9 mRNA in colorectal cancer tissue. There was a strong correlation between the expression of MMP-9 in tumor cells and liver metastasis. The expression of mRNA for TIMP-1 in stromal cells in cases associated with liver metastasis was significantly higher than that in cases without liver metastasis. However, in tumor cells, predominant expression of MMP-9 mRNA was observed in all cases associated with liver metastasis. These results suggest that MMP-9 might play an important role in hematogenous metastasis in colorectal cancer and that the balance between the production of MMP-9 and TIMP-1, in particular in tumor cells, is important as one of the pathogenesis of tumor metastasis.
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PMID:[Significance of MMP-9 and TIMP-1 production during liver metastasis in colorectal cancer]. 763 24

We have explored the tissue localization of extracellular matrix metalloproteinases MMP-1 (fibroblast collagenase), MMP-2 (72-kDa gelatinase/Type IV collagenase), MMP-3 (stromelysin), MMP-8 (polymorphonuclear leukocyte collagenase) and MMP-9 (92-kDa gelatinase/Type IV collagenase) in the tissues around loose hip prostheses. The findings were compared with those in synovial tissues obtained from patients with a fractured femoral neck. MMP-type specific antisera were applied in the sensitive avidin-biotin-peroxidase complex methods. MMP-1 was found in monocyte/macrophages, fibroblasts, and vascular endothelial cells in both interface tissues between bone and acetabular components and the pseudocapsular tissues obtained from loosening of hip prostheses. In these tissues, MMP-8 was occasionally found, but only in polymorphonuclear leukocytes. Cells showing immunoreactivity to 72- and 92-kDa gelatinase/Type IV collagenase, MMP-2 and MMP-9, respectively, and stromelysin, MMP-3, were abundant in both interface and pseudocapsular tissues in loose hip prostheses. In contrast, in hip fractures, immunoreactivity to MMP-1, 2, 3, and 9 was weak and only observed in synovial tissues. Immunoreactivity to MMP-8 was confined to polymorphonuclear leukocytes attached to the synovial membrane or in the infiltrate around blood vessels in the subsynovial connective tissues. The finding of MMP-1, 2, 3, and 9 in the tissues around loose hip prostheses suggests that they play a role in the weakening of connective tissues, and this leads to loosening.
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PMID:Extracellular matrix metalloproteinases around loose total hip prostheses. 804 79

Interstitial collagenase (EC 3.4.24.7, matrix metalloproteinase-1, MMP-1) is synthesized and secreted by many cells, and plays an important role in a wide variety of pathophysiological degradation processes of extracellular matrices. The activity of MMP-1 is regulated by tissue inhibitors of metalloproteinases, TIMP-1 or TIMP-2, which form a non-covalent complex with the active enzyme. We raised monoclonal antibodies against zymogen of MMP-1, proMMP-1 purified from human skin fibroblasts. The antibodies recognized both precursor and active forms of MMP-1, but did not cross-react with 72-kDa and 92-kDa gelatinase/type IV collagenases or stromelysin-1. A specific and sensitive one-step sandwich enzyme immunoassay for human MMP-1 was developed using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The assay can be completed within 1 h (30 min for immunoreaction and 15 min for color development) and the sensitivity is 0.12 microgram/l with the linearity between 0.12 and 10 micrograms/l. Active MMP-1 shows 1.3-fold higher absorption at 492 nm than proMMP-1. However, the recognition rate of MMP-1 is decreased to approximately 50% and < 3% for the MMP-1-TIMP-1 and MMP-1-TIMP-2 complex forms, respectively. The MMP-1 levels in human sera from 120 healthy subjects are shown to be in the range of 8.5 +/- 5.2 micrograms/l (mean +/- S.D.) and the levels of 95% of the samples range from 0 to 20 micrograms/l.
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PMID:A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 1 (interstitial collagenase) using monoclonal antibodies. 830 49

A quantitative nonisotopic solution assay for gelatinases and inhibitors was developed using biotinylated gelatin as enzyme substrate. In this assay, residual biotinylated substrate is sandwiched between avidin-coated plates and streptavidin-peroxidase and is quantified by the peroxidase reaction. This assay was useful for measuring gelatinase activities and defining the activities of gelatinase inhibitors. When 23 tetracycline analogues were compared, significant differences in gelatinase B inhibition were found between various compounds. 4-epioxytetracycline base, 4-epichlortetracycline, meclocyclinesulfosalicylate, and unmodified metacycline and minocycline proved to be the most potent gelatinase B (EC 3.4.24.35) inhibitors. The gelatinase B inhibitory activity of tetracyclines was clearly dissociated from their antimicrobial activity. The effect of high-molecular-weight inhibitors, such as monoclonal antibodies, was also demonstrable in the microtiter plate assay. In view of the pathophysiological function of gelatinases, the definition of gelatinase inhibitors with known efficacy, safety, and side effects is crucial for the treatment of diseases such as rheumatoid arthritis and multiple sclerosis. Particular tetracyclines fulfil these criteria and the described assay is useful for defining other gelatinase-inhibiting lead compounds.
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PMID:The gelatinase inhibitory activity of tetracyclines and chemically modified tetracycline analogues as measured by a novel microtiter assay for inhibitors. 867 93

Matrix metalloproteinases (MMPs) and, specifically, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are strongly associated with malignant progression and matrix remodeling. These enzymes are a subject of intensive studies involving screening of comprehensive chemical libraries of synthetic inhibitors. There is no simple method available for measurement of activity of gelatinases and related MMPs. Here, we report a simple, inexpensive, and highly sensitive assay for MMP activity. The assay performed in a 96-well microtiter plate format employs biotin-labeled gelatin (denatured collagen type I) as a substrate. Following the substrate cleavage, only the proteolytic fragments bearing biotin moieties are captured by streptavidin coated on the plastic surface and the captured fragments with at least two biotin molecules should be revealed by streptavidin conjugated with horseradish peroxidase. The frequency of lysine residues is low in collagen type I relative to the MMP cleavage sequences (PXGX). Accordingly, the majority of the cleavage products must be devoid of biotin or possess only one biotin group. Both of these types of fragments cannot be recognized by the horseradish peroxidase-streptavidin conjugate. Therefore, higher gelatinolytic activity is associated with lower signal in the assay. This 2-h assay allows identification of gelatinolytic activity of MMP-2 in concentrations as low as 0.16 ng/ml. The sensitivity of this ELISA-like assay is comparable to that of gelatin zymography, a method widely used to detect gelatinases. However, in contrast to zymography, the assay directly measures the enzymatic activity of MMP samples. The gelatinolytic activity assay permits efficient analyses and screening of the MMP inhibitor panels and allows quantitation of gelatinolytic activity of various MMPs in solution as well as on cell surfaces.
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PMID:Determination of matrix metalloproteinase activity using biotinylated gelatin. 1103 85

In patients with sudden unexpected cardiac death, there is a relationship between the interstitial fibrosis of the myocardium and matrix molecules with a role in global remodeling of the cardiac stroma. Tissue samples of left ventricular myocardium from 17 middle-aged patients with sudden cardiac death, following acute or chronic ischemic cardio(myo)pathies, were analyzed using standard HE stain and the indirect tristadial ABC peroxidase immunohistochemical method for a panel of four antibodies involved in the dynamic remodeling of extracellular matrix: matrix metalloproteinase 9 (MMP9), tenascin X (Tn-X), TGF-b, CD54 (ICAM-1), together with simultaneously assessment of troponin in myocardic fibers. The most sensitive reaction was noticed for ICAM-1 in 71% of cases, followed by MMP9 in 59% of cases and TGF-b in 47% of cases (with great specificity for capillary vessels), in the extracellular matrix of the residual cardiomyocytes. A direct correlation, statistically significant was recorded between troponin and MMP9 (r = 0.65, p = 0.01), troponin and ICAM-1 (r = 0.31, p = 0.02), respectively ICAM-1 and tenascin (r = 0.72, p = 0.01). The extensive expression of ICAM-1 in the extracellular matrix from the perilesional area probably plays a role in the stimulation of new developing adhesion substrates between residual cells and adjacent stroma, while the over expression of troponin in the residual cardiomyocytes is accompanied by a high expression of MMP9 in the myocardic interstitium, with heterogeneous remodeling of the ventricular stroma. The simultaneous IHC expression of tenascin and ICAM-1 suggests a colocalization required for the nerve sprouting in the residual myocardium and for developing new focal cell-matrix adhesion contacts.
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PMID:Simultaneous immunophenotypical assessment of troponin and extracellular matrix molecules in myocardium of patients with sudden cardiac death. 1922 53

An immunohistochemical study of matrix metalloproteinases (MMP-2 and MMP-9) or gelatinase (gelatinase A and gelatinase B) was performed on the seminal vesicles and ventral prostate of the Libyan jird (Meriones libycus) collected in the Beni-Abbes area during breeding period (spring and early summer), during resting phase (late summer, autumn, winter) and from castrated animals in the spring. The work was done using the indirect immunohistochemistry protocol by amplification with streptavidin-biotin-peroxidase and AEC as chromogen. In the seminal vesicles, during the breeding period, an important immunohistochemical signal of MMP-2 and MMP-9 was observed in epithelial cells and smooth muscle cells (SMC) without any immunoexpression in the extracellular matrix (ECM) and secretion. During resting phase and in thirty days castrated Meriones libycus, the MMP-2 and MMP-9 immunoexpression was weak in the epithelial cells and persisted with the same intensity in the SMC. The ECM, with no immunostaining in active season, showed a pronounced immunoresponse of both the two gelatinase. Three days after castration, the MMP-9 immunohistochemical reaction in epithelial cells and SMC was as intense as during active season. A prolonged castration of 50 and 90 days resulted in the maintenance of the MMP-9 immunostaining in epithelial cells and SMC and its disappearance from the ECM, suggesting a slow process of regression. During the breeding period, in the ventral prostate, MMP-2 immunostaining was more important in the SMC than in epithelial cells. The MMP-9 immunoexpression pattern was the opposite, the epithelial cells showed a higher immunoreaction than SMC. ECM and secretion lacked MMP-2 and MMP-9 immunostaining. The ventral prostate lumen contained a granular secretion without any gelatinase immunolabelling and was hollowed by empty circular forms reflecting the disappearance of the product in these areas. Part of the secretion showed a positive MMP-2 and MMP-9 immunoreaction. The latter was subsequently filled and seemed involved in the progression of the secretion in the tubules, preventing their filling. In resting phase and in animals castrated since thirty days, the immunoreactivity of both the two gelatinases was maintained in the epithelial cells and in the SMC, and was absent in the ECM. The gelatinases are involved in the seasonal reproductive cycle of Meriones libycus.
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PMID:Immunoexpression of gelatinase (MMP-2 and MMP-9) in the seminal vesicles and ventral prostate of Libyan jird (Meriones libycus) during the seasonal cycle of reproduction. 2023