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)

Gelatinase and proteoglycanase are metalloproteinases that govern extracellular matrix remodeling. In the present study, immature rats were primed with eCG (20 IU) and hCG (10 IU). Ovarian gelatinase and proteoglycanase activity were determined at the time of hCG administration (0 h) as well as 4, 8, and 12 h later. Gelatinase and proteoglycanase were extracted by homogenization in Triton and by heating (i.e., heat extraction). An aliquot of the heat extract was reduced and alkylated to destroy metalloproteinase inhibitors. Heat extracts not reduced and alkylated showed low levels of gelatinase and proteoglycanase activity that did not change at the different time points. However, with reduction and alkylation, gelatinolysis increased approximately 4-fold (p less than 0.05) at 4 h, 8 h, and 12 h after hCG priming. Proteoglycanase activity increased approximately 2-fold (p less than 0.05) between 0 and 8 h and declined at 12 h after hCG. The ovarian gelatinolytic activity was due to a metalloproteinase as demonstrated by the inhibition of enzyme activity by phenanthroline and EDTA (97.1 +/- 0.7% and 97.4 +/- 0.6% inhibition respectively). Proteoglycanase activity was not inhibited by phenanthroline (11.5 +/- 3.5%), suggesting that the enzyme activity was not specifically a metal-dependent enzyme. Gelatin gel zymography of the ovarian extracts demonstrated four predominant and distinct gelatin-degrading enzymes of 78, 72, 66, and 62 kDa, similar to the size of gelatinase. The present findings demonstrate a periovulatory increase in ovarian gelatinolytic and proteglycanase activity that may play a pivotal role in connective tissue remodeling associated with ovulation.
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PMID:Gelatinase and proteoglycanase activity during the periovulatory period in the rat. 131 Dec 10

During the involution of the mammary gland there is destruction of the basement membrane as the secretory alveolar structures degenerate. Immunofluorescence staining of sections of rat mammary gland with antibodies to 72 KD gelatinase (MMP-2) and stromelysin (MMP-3) revealed increased production of these two proteinases during involution. This increased expression was mostly restricted to myoepithelial cells. Increased expression during involution was also demonstrated by immunoblotting techniques. Gelatin zymography indicated that the predominant metalloproteinase present in involuting rat mammary glands was a 66 KD gelatinase.
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PMID:Enhanced synthesis of gelatinase and stromelysin by myoepithelial cells during involution of the rat mammary gland. 131 55

This study was performed to characterize the matrix metalloproteinases (MMPs) produced during the degradation of cotton-wrapped cartilage, implanted into the murine air pouch. One, two or three weeks following cartilage implantation, proteins were extracted from the granulation tissue and MMP activities were measured. Although collagenase-, gelatinase- and stromelysin-like activities were detected at each time point, gelatinase activity was by far the most prominent. These enzymes were inhibited by EDTA, but not by NEM or PMSF, indicating that these proteinases were metalloproteinases. Gelatin zymography revealed several lysis zones amongst which a major 92-kDa band shifted to 83- and 68-kDa species during the course of implantation. The emergence of these species coincided with enhanced gelatinolytic activity and collagen loss from the implanted cartilage.
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PMID:Gelatinase is the main matrix metalloproteinase involved in granuloma-induced cartilage degradation. 133 18

To clarify the destruction of connective tissue in ulcerated regions, collagenase and gelatinolytic activities in homogenates of rat acetic acid-induced ulcers were examined. Gelatinolytic activity in the ulcerated regions was significantly higher than that in normal tissues. Collagenase, however, was not detectable. Gelatin-gel-electrophoresis showed that the gelatinolytic activity was due to several species, some of which crossreacted with a sheep anti-(rabbit prostromelysin) antibody. The H2-blocker, famotidine, significantly depressed the gelatinolytic activity in the ulcerated regions. Thus, both stromelysin and gelatinolytic enzymes may play important roles in the degradation of the basement membrane, especially type IV collagen.
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PMID:Characterization of metalloproteinases in rat gastric tissues with acetic acid-induced ulcers. 259 86

Connective tissue matrix-degrading metalloproteinases play an important role in cancer invasion. In this report we describe the isolation of a metalloproteinase exhibiting both type IV collagenolytic and gelatinolytic activities from the conditioned medium of NIH-3T3 fibroblasts transformed with DNA containing an activated c-Harvey-ras oncogene from T24 bladder cancer cells. This tumor proteinase was purified by anion exchange chromatography, zinc-chelate Sepharose chromatography, and gel permeation chromatography. The final product was homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (relative molecular mass = 67,000). Gelatin zymography revealed two bands of gelatinolytic activity, corresponding to molecular weights of 67,000 and 62,000. Upon immunoblotting with the use of an affinity-purified polyclonal rabbit antibody to a peptide region of type IV collagenase that lacks homology with interstitial collagenase or stromelysin, the purified tumor enzyme was identified as type IV collagenase.
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PMID:Purification of a gelatin-degrading type IV collagenase secreted by ras oncogene-transformed fibroblasts. 284 10

In this paper, we present a longitudinal study on metalloproteinases in wound-fluid samples collected from three patients with partial- to full-thickness burn wounds. Gelatin zymography showed that 92-kDa gelatinase (MMP-9) and its 225-kDa complex could be detected in burn fluid beginning as early as 4-8 h after injury. Marked increases in MMP-9 levels as well as activation of the proenzyme occurred between day 0 and day 2. The 72-kDa gelatinase (MMP-2) proenzyme was not detected until day 2 and activated enzyme did not appear until day 4. Stromelysin (MMP-3), both proenzyme and activated-enzyme forms, was first observed on day 4. Fluid-phase proteinase activity detected by azocoll degradation roughly corresponded with the level of stromelysin rather than the gelatinases. Our results provide evidence for a regulated metalloproteinase activation cascade following acute traumatic injury and demonstrate in vivo expression of metalloproteinase activity.
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PMID:Metalloproteinase activation cascade after burn injury: a longitudinal analysis of the human wound environment. 796 52

We have examined the correlation between matrix metalloproteinase (MMP) expression and metastatic properties of a low metastatic osteosarcoma cell line, osteosarcoma takase (OST), under stimulation by tumour necrosis factor alpha (TNF alpha). In vivo, OST cells exhibited significantly increased colonization in the lungs of nude mice in a dose-dependent manner when they were treated by TNF alpha prior to injection. In vitro, TNF alpha enhanced tumour cell invasion through the reconstituted basement membrane in a transwell chamber up to 2.5-fold. Gelatin zymography and sandwich enzyme immunoassays demonstrated marked production of MMP-9 [92-kDa gelatinase/type IV collagenase (gelatinase B)] but not MMP-2 [72-kDa gelatinase/type IV collagenase (gelatinase A)], MMP-3 (stromelysin-1) or MMP-7 (matrilysin). Motility of the tumour cells and adhesion to cultured endothelial cells were slightly increased by the TNF alpha treatment up to 1.6-fold and 1.4-fold, respectively, while the growth rate was decreased. These results suggest that upregulation of MMP-9 together with enhanced motility and endothelial adhesion contribute to the increased metastatic ability of OST cells induced by TNF alpha treatment.
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PMID:Expression of matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) induced by tumour necrosis factor alpha correlates with metastatic ability in a human osteosarcoma cell line. 803 35

Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.
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PMID:Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion. 857 23

Porphyria cutanea tarda is characterized by severe connective tissue damage in sun-exposed skin. The regulated synthesis and degradation of the extracellular matrix by various matrix metalloproteinases (MMPs) determine its amount and composition within the skin. In this study, we therefore asked whether long-wave ultraviolet irradiation (340-450 nm) in conjunction with uroporphyrin I could modulate the synthesis of MMPs with substrate specificities for dermal (collagens I, III, V; proteoglycans) and basement membrane components (collagens IV, VII; fibronectin; laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases is also affected. After irradiation of uroporphyrin-pretreated fibroblasts, specific mRNAs of MMP-1 and MMP-3 increased concomitantly up to 2.7-fold compared with ultraviolet-irradiated cells and up to 10-fold compared with mock-irradiated or uroporphyrin I-treated controls. In contrast, mRNA levels of tissue inhibitor of metalloproteinases remained unaltered. Similar results were obtained by immunoprecipitation. Gelatin and casein zymography revealed increased proteolytic activity of MMP-2 and MMP-3 in blister fluids of patients with porphyria cutanea tarda, indicating that similar events may occur in vivo. Using deuterium oxide as enhancer and sodium azide as quencher of singlet oxygen, we could increase or reduce MMP synthesis, suggesting that singlet oxygen is the major intermediate in the upregulation of MMPs after irradiation of uroporphyrin-pretreated fibroblasts. Taken together, our results show that ultraviolet irradiation alone, and to a greater extent in conjunction with uroporphyrin I, results in an unbalanced synthesis of MMPs that may contribute to the destruction of the dermis and basement membrane, leading to blistering and accelerated photoaging in porphyria cutanea tarda patients.
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PMID:Photosensitization of uroporphyrin augments the ultraviolet A-induced synthesis of matrix metalloproteinases in human dermal fibroblasts. 875 77

We examined production and tissue localization of matrix metalloproteinase (MMP)-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B), tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in human breast carcinomas. In more than half of the cases, MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were immunolocalized in carcinoma cells and MMP-2 was on the carcinoma cell membranes as well, whereas MMP-3 was positively stained in less than 15% of the cases. MMP-1 staining in carcinoma cells was significantly higher in scirrhous carcinoma than in other types of carcinoma. MMP-9 expression was remarkably higher in the carcinoma cases with lymphnode metastasis than in the non-metastatic cases. MMP-3 was mainly expressed in T-lymphocytes infiltrated in the tumor stroma. Stromal fibroblasts were positive for all these MMPs except for MMP-3. The TIMP-1 levels released into the culture media by carcinoma tissues were significantly lower than those by fibroadenoma tissues, although there were no significant differences in the levels of MMP-1, MMP-2, MMP-9 and TIMP-2. Gelatin zymographical analyses showed that the activation rate of the zymogen of MMP-2 (proMMP-2) is significantly higher in the more advanced carcinoma group with lymphnode metastasis than in the metastasis-negative and fibroadenoma groups. These data indicate that MMP-1, MMP-2 and MMP-9 are highly expressed in human breast carcinoma tissue and suggest that activation of proMMP-2 may be an indicator of lymphnode metastasis of the breast carcinoma.
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PMID:Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas. 876 24


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