Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we have identified and characterized metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) in human plasma. Treatment of plasma with trypsin or aminophenylmercuric acetate resulted in activation of latent gelatinolytic activity. Fractionation of plasma by gelatin Sepharose chromatography resulted in the isolation of 72 kDa and 92 kDa gelatinases/type IV collagenases. The 72 kDa gelatinase was purified by gel filtration chromatography. Stromelysin-1 was isolated from plasma by Matrex green A affinity chromatography. Immunoblotting of plasma fractions with antibodies to unique peptide regions of human gelatinases differentiated the 72 kDa gelatinase from the 92 kDa gelatinase. Antibodies to the amino terminal peptides of each enzyme were used to determine that plasma gelatinases circulate as latent proenzymes. Immunoblotting with antibodies directed against human stromelysin identified a 57 kDa stromelysin. TIMP-1 (28 kDa) and TIMP-2 (21 kDa) were also identified by immunoblotting of gelatin Sepharose bound plasma proteins using non-crossreacting antibodies to each protein.
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PMID:Characterization of metalloproteinases and tissue inhibitors of metalloproteinases in human plasma. 146 8

The processing of culture medium of rabbit synovial fibroblasts led to the isolation of three stromelysin-1 (MMP-3) cleavage products: A 31-kDa protein, which represents a C-truncated latent stromelysin-1, an active stromelysin-1 of 21 kDa, that originates from the 31-kDa proform by activation. A third protein had a molecular mass of 25 kDa representing the C-terminal part of prostromelysin-1 and is missing in the C-truncated latent stromelysin-1. The activation process of human prostromelysin-1 in vitro is known to lead to an active stromelysin-1 with a relative molecular mass of 45 kDa by removing the N-terminal prodomain. This active stromelysin-1 is further processed to a lower molecular mass active form of 28 kDa. Our results obtained for the highly homologous rabbit stromelysin-1 indicate that another activation pathway is possible. In a first step prostromelysin-1 is hydrolysed between Met261-Glu generating a C-truncated latent stromelysin-1, which is activated by cleavage of the Thr83-Phe bond to the 21-kDa stromelysin-1. The latent C-truncated stromelysin-1 is slowly converted even at 4 degrees C into the active form. In the presence of 50 microM ZnCl2 this activation was prevented for at least three weeks. The activation rate is largely enhanced by aminophenylmercury acetate and especially by trypsin. The differences of the 21-kDa stromelysin-1 to a 28-kDa stromelysin-1 isolated from human rheumatoid synovial fluids described earlier are discussed.
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PMID:Isolation of latent 31-kDa C-truncated stromelysin and 21-kDa stromelysin from rabbit synovial fibroblasts: an alternative activation pathway for stromelysin. 806 May 32

Matrix vesicles (MVs) are enriched in matrix metalloproteinases (MMPs) capable of degrading proteoglycans. The aim of the present study was to identify which MMPs are present in MVs and determine whether these MMPs are regulated by 1,25-(OH)2D3 [1,25] and 24,25-(OH)2D3 [24,25]. To do this, growth zone (GC) and resting zone (RC) chondrocytes were isolated from rate costochondral cartilage and placed into culture. At confluence, GCs were treated with 1,25 and RCs with 24,25 for 24 hours. MVs, plasma membranes (PMs), and conditioned media were then collected from the cultures. RTPCR demonstrated the presence of mRNA for stromelysin-1 and 72 kDa gelatinase in both RCs and GCs, Casein zymography revealed activity at M(r) 48 and 28 kDa in MV, but not PM or conditioned media; Western analysis confirmed that this activity was stromelysin-1. Gelatinolytic activity, at low levels, was also found in MVs, but not PMs or conditioned media. When enzyme activity was measured using a proteoglycan bead assay, it was found that both GCs and RCs produced MVs and PMs containing neutral metalloproteinase. Both cells also produced MVs and PMs containing plasminogen activator. The addition of 1,25 to GCs caused a significant 4- to 5-fold increase in metalloproteinase activity in MVs, but not PMs. In contrast, MVs from cultures of RCs treated with 24,25 contained decreased metalloproteinase activity; enzyme activity in PMs was unaffected by 24,25. Plasminogen activator in MVs from RC was increased by treatment with 24,25, while MV enzyme activity was decreased after treatment of GC cultures with 1,25. This study shows that both RCs and GCs produce stromelysin-1 and 72 kDa gelatinase and that these enzymes are preferentially localized in MVs. Further, MMP and plasminogen activator activities in MVs and PMs are regulated by vitamin D metabolites.
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PMID:Vitamin D regulation of metalloproteinase activity in matrix vesicles. 908 72

We report the discovery, cloning, and characterization of a novel human matrix metalloproteinase 26 (MMP-26) (matrixin) gene, endometase, an endometrial tumor-derived metalloproteinase. Among more than three million expressed sequence tags sequenced, the endometase gene was only obtained from human endometrial tumor cDNA library. Endometase mRNA was expressed specifically in human uterus, not in other tissues/cells tested, e.g. testis, heart, brain, lungs, liver, thymus, and melanoma G361. Endometase protein has a signal peptide, a propeptide domain, and a catalytic domain with a unique "cysteine switch" propeptide sequence, PHCGVPDGSD, and a zinc-binding motif, VATHEIGHSLGLQH. Endometase is 43, 41, 41, and 39% identical to human metalloelastase, stromelysin, collagenase-3, and matrilysin, respectively. The zymogen was expressed and isolated from Escherichia coli as inclusion bodies with a molecular mass of 28 kDa. The identity and homogeneity of the recombinant protein was confirmed by protein N-terminal sequencing, silver stain, and immunoblot analyses. The pro-enzyme was partially activated during the folding process. Endometase selectively cleaved type I gelatin and alpha(1)-proteinase inhibitor; however, it did not digest collagens, laminin, elastin, beta-casein, plasminogen, soybean trypsin inhibitor, or Bowman-Birk inhibitor. It hydrolyzed peptide substrates of matrixins and tumor necrosis factor-alpha converting enzyme. Endometase may selectively cleave extracellular matrix proteins, inactivate serpins, and process cytokines.
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PMID:Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor. 1080 41

We investigated the expression and distribution of osteopontin in mouse salivary glands. Western blot analysis showed intense positive bands at the predicted molecular mass (about 60 kDa) in mouse parotid and sublingual glands. However, a cross-reacted band around 30 kDa was strongly detected in submandibular glands. Indirect immunofluorescent analysis showed that osteopontin was localized at the luminal (apical) membranes of the acinar cells in parotid and sublingual glands. However, it was not detected in acinar cells of submandibular glands. No expression was found in ductal cells of any glands. We also examined the expression of matrix metalloproteinase (MMP)-3 and -7. In parotid gland, MMP-3 was observed at 57 kDa, indicating a latent form, but MMP-7 was not detected. In contrast, MMP-7 definitely was observed at 28 kDa area in submandibular gland, whereas MMP-3 was not detected. These results suggest that osteopontin localizes at luminal sites of acinar cells and may be associated with saliva secretion in mouse salivary gland. It is also suggested that osteopontin may be cleaved by MMP-7 in mouse submandibular gland.
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PMID:Expression and distribution of osteopontin and matrix metalloproteinase (MMP)-3 and -7 in mouse salivary glands. 1456 97