Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.35 (matrix metalloproteinase 9)
2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular matrix turnover in the trabecular meshwork may play a role in regulating aqueous humor outflow. Laser trabeculoplasty is a common treatment for open-angle glaucoma. The mechanism of this treatment is not understood. We investigated changes in the levels and expression of the matrix metalloproteinases and their tissue inhibitors (TIMPs) in this tissue using cultured human anterior segment explants and standard clinical-parameter laser treatment. Medium gelatinase A activity levels are relatively high for sham-treated controls and are not changed dramatically following laser treatment. Medium gelatinase B and stromelysin activity levels are low in sham-treated explants and increase significantly by 24 h after treatment. TIMP1 levels, as assessed by immunoblots of Western transfers, are initially low. However, by 24 h TIMP1 levels have increased significantly. Using semi-quantitative reverse transcription and the polymerase chain reaction, mRNA levels of stromelysin, gelatinase B and TIMP1 are shown to increase after laser treatment, while gelatinase A and TIMP2 remain relatively constant. The increases in trabecular stromelysin and gelatinase B in response to laser trabeculoplasty may have important implications for the mechanism of action of this treatment for open-angle glaucoma.
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PMID:Early changes in matrix metalloproteinases and inhibitors after in vitro laser treatment to the trabecular meshwork. 758 99

Numerous studies have reported a correlation between the production of gelatinases A and B by cancer cells and invasive and metastatic potential. It has been suggested that the expression of gelatinase A (72-kDa type IV collagenase) is associated more closely with the metastatic phenotype of malignant cells in vitro and in vivo than that of gelatinase B (92-kDa type IV collagenase). We have established a rat bladder carcinoma cell line, MYU3L, which is tumorigenic and locally invasive but is not metastatic to the distal organs in nude mice. The MYU3L cell line secretes pro-gelatinase B but not any detectable level of pro-gelatinase A. We undertook the present study to determine whether over-expression of gelatinase A can affect the metastatic potential of MYU3L cells. We transfected MYU3L cells with an expression vector containing human pro-gelatinase A cDNA under the transcriptional control of the SR alpha promoter. Two stable transfectants over-expressing gelatinase A activity were isolated. We assessed the biological behavior of the transfectants by an orthotopic site (urinary bladder) inoculation and an i.v. injection in nude mice. Our results demonstrate that the induced expression of human gelatinase A enzyme markedly accelerates the metastatic phenotype of the rat bladder carcinoma cell line MYU3L. Our results suggest that gelatinase A produced by tumor cells plays a major role in the metastatic process.
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PMID:Marked acceleration of the metastatic phenotype of a rat bladder carcinoma cell line by the expression of human gelatinase A. 759 Dec 68

Loss of negative growth regulation and high invasive potential are neoplastic traits often associated with abnormal expression of matrix metalloproteinases (MMPs). We previously found MMP-3 (stromelysin/transin) was secreted by quiescent rat Schwann cell cultures and expressed potent antiproliferative activity. In the present study we observed that human Schwann cells and cutaneous neurofibroma Schwann cell cultures secreted abundant MMP-3 and their proliferation was inhibited by autologous and rat Schwann cell conditioned media. Antiproliferative activities were depleted by immunoadsorption with anti-stromelysin antibodies. In contrast, plexiform neurofibroma cultures did not secrete MMP-3 and failed to respond to Schwann cell antiproliferative activities associated with MMP-3. Quiescent Schwann cells constitutively secreted low levels of MMP-2 (gelatinase A) and showed a low invasion potential in filter-based assays of basement membrane invasion. Cyclic AMP elevation, which profoundly influences cell differentiation, increased the invasion potential of rat Schwann cells and caused a corresponding increase in secretion of MMP-2. Schwann cells immortalized by protracted elevation of cAMP, as well as a schwannoma cell line (D6P2T), also rapidly invaded a reconstituted basement membrane and over-expressed MMP-2. Similarly, neurofibroma Schwann cells were highly invasive and secreted up to 10-fold more MMP-2 than normal human Schwann cells. Additionally, only cutaneous neurofibroma Schwann cell cultures secreted MMP-9 (gelatinase B) and MMP-1 (interstitial collagenase) and also invaded native type I collagen barriers. Cultures of normal Schwann cells and plexiform neurofibroma tumor expressed little or no MMP-1 and did not invade type I collagen barriers. These results suggest a role for MMPs in the control of proliferation and invasion by Schwann cells and in the formation of peripheral nerve sheath tumors.
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PMID:Differences in proliferation and invasion by normal, transformed and NF1 Schwann cell cultures are influenced by matrix metalloproteinase expression. 760 93

To understand the roles of intracellular calcium levels on gelatinase/type IV collagenase expression, we analyzed the effects of calcium ionophores on the expression of 92- and 72-kDa gelatinases (MMP-9 and MMP-2) in human fibrosarcoma cells (HT-1080). Calcium ionophores ionomycin and A23187 reduced the levels of pericellular gelatinolytic activity in both untreated and phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-alpha (TNF alpha)-stimulated cells as determined by degradation of radiolabeled gelatin. Gelatin zymography and immunoblotting revealed a dose-dependent decrease in the levels of secreted 92-kDa gelatinase, which was paralleled by a decrease of its mRNA. Treatment of cells with thapsigargin caused similar decreases of 92-kDa gelatinase mRNA and protein. The decrease of 92-kDa gelatinase expression was due to lower transcription rate as determined by transfection assays with 92-kDa gelatinase/luciferase construct. The expression of 72-kDa gelatinase was only slightly decreased by ionophores. Treatment of HT-1080 cells with PMA, TNF alpha, or concanavalin A resulted in the conversion of 72-kDa gelatinase proenzyme to its presumed 64- and 62-kDa active forms as determined by gelatin zymography and immunoblotting. Simultaneous treatment with the ionophores or thapsigargin resulted in inhibition of PMA-induced gelatinase activation. The expression of membrane-type matrix metalloproteinase, a potential activator of 72-kDa gelatinase, was not affected by ionophores. The results indicate that calcium ionophores decrease gelatinolysis by repressing both the expression of 92-kDa gelatinase and the activation of the 72-kDa gelatinase.
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PMID:Calcium ionophores decrease pericellular gelatinolytic activity via inhibition of 92-kDa gelatinase expression and decrease of 72-kDa gelatinase activation. 761 67

The gene expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was studied in human gliomas in vivo and in vitro to evaluate their roles in glioma invasion. Simultaneous expression of one to four MMP genes and two TIMP genes was found in 17 surgical glioma specimens, and one MMP (gelatinase A) gene and two TIMP genes were simultaneously expressed in tissue of three brains. The concomitant overexpression of gelatinase A, gelatinase B, and occasional matrilysin genes was associated with the malignancy of gliomas and accompanied by overexpression of the TIMP-1 gene. In five human glioma cell lines, gelatinase A, TIMP-1, and TIMP-2 genes were constitutively expressed in alll cell lines: the matrilysin gene in three cell lines; the stromelysin gene in two cell lines; and the interstitial collagenase gene in one cell line. There was a clear difference in the expression of gelatinase B and stromelysin genes between surgical glioma specimens and glioma cell lines: the gelatinase B gene was not expressed constitutively in vitro but was overexpressed in vivo, whereas the stromelysin gene was not expressed in vivo but was expressed in some cell lines. To find the cause of that difference in vivo and in vitro, the transcriptional regulations of MMP and TIMP genes by tumor promoter, growth factors, or cytokines were studied in vitro. Interstitial collagenase, gelatinase B, stromelysin, and TIMP-1 genes were upregulated in many cell lines by phorbol-12-myristate-13-acetate (PMA) and in some cell lines by epidermal growth factor, tumor necrosis factor-alpha, or interleukin-1 beta. Transforming growth factor-beta 1 (TGF beta 1) upregulated gelatinase A and matrilysin genes in some cell lines, and there were no clear responses from any MMP and TIMP genes to interleukin-6. Thus, the transcriptional modulation of MMP genes by these growth factors and cytokines seemed insufficient to explain the difference in gelatinase B and stromelysin gene expressions in vivo and in vitro and was suggestive of the genetic alteration of glioma cells in vitro, the heterogeneous cell population in glioma tissues, or both. Furthermore, the in vitro invasion of glioma cells through Matrigel in response to PMA, TGF beta 1, or TIMP-1 was assessed by chemoinvasion assay. In most cell lines, invasion was significantly stimulated by PMA or TGF beta 1 but suppressed by TIMP-1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. 761 76

The risk of rupture of an abdominal aortic aneurysm increases with aortic diameter. To obtain insight into the pathological processes associated with the vascular remodeling that accompanies aortic dilatation, we compared the histological features and the activity of matrix metalloproteinases (MMPs) in biopsies from 21 small (4.0 to 5.5 cm in diameter) and 45 larger abdominal aortic aneurysms. The histological feature most clearly associated with enlarging aneurysm diameter was a higher density of inflammatory cells in the adventitia, P = .018. This inflammation was nonspecific, principally macrophages and B lymphocytes. Fibrosis of the adventitia provided compensatory thickening of the aortic wall as the aneurysm diameter increased. A combination of zymography and immunoblotting identified gelatinase A (MMP-2) as the principal metallogelatinase in small aneurysms, whereas zymography indicated an increasing activity of gelatinase B (MMP-9) in large aneurysms. Homogenates prepared from both small and large aneurysms had similar total activity against gelatin or type IV collagen. However, the concentration of gelatinase A, determined by immunoassay, was highest for small aneurysms: median concentrations, 385, 244, and 166 ng/mg protein for small aneurysms, large aneurysms, and atherosclerotic aorta, respectively. Immunolocalization studies indicated that gelatinase A was concentrated along fibrous tissue of both the acellular media and the atherosclerotic plaque. The recruitment of inflammatory cells into the adventitia, with subsequent elaboration of metalloproteinases, including gelatinase B, may contribute to the rapid growth and rupture of larger aneurysms.
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PMID:Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. 762 8

Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3, class-I major histocompatibility antigen). Further molecular analysis indicated that the anti-tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation-inducers with potential use in cancer intervention.
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PMID:Cinnamic acid: a natural product with potential use in cancer intervention. 762 77

The adult mammalian temporomandibular joint (TM) disc is a fibrocartilaginous tissue that undergoes normal developmental remodeling, requiring removal of the existing extracellular matrix and its replacement by new matrix macromolecules. This remodeling is probably mediated by matrix-degrading enzymes, but to date none has been demonstrated in association with the TMJ disc. We characterized, identified, and determined the regulation of proteinases and proteinase inhibitor (PIs) synthesized by TMJ disc cells in organ and cell cultures. TMJ discs were retrieved from 14-week-old male NZW rabbits and both tissue- and disc-derived cells were cultured in serum-free medium. The conditioned media were retrieved at 12-hour intervals and assayed for proteinases and PIs in gelatin- and casein-impregnated polyacrylamide gels. Three proteinases with gelatinolytic activities at 92 kDa, 72 kDa, and 42/57 kDa and one caseinolytic activity at 51/54 kDa were detected. All were inhibited by 1,10-1 phenanthroline, thus characterizing these enzymes as matrix metalloproteinases (MMPs), most likely 92-kDa gelatinase (proMMP-9), 72-kDa gelatinase (proMMP-2), procollagenase (proMMP-1), and prostromelysin (proMMP-3). The identity of the latter two MMPs was confirmed by Western blots. Two PIs and 30 kDa and 20 kDa, probably tissue inhibitors of metalloproteinase (TIMP) and TIMP-2, were observed on reverse zymograms. TPA, a protein kinase-C agonist, increased the expression of 92-kDa gelatinase and 30-kDa PI by both explanted discs and isolated disc cells. The profile of MMPs constitutively expressed by disc cells is similar to that of synovial fibroblasts but different from that of chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization and identification of proteinases and proteinase inhibitors synthesized by temporomandibular joint disc cells. 762 41

The literature has revealed variations in the protocols for myoblast cultures, and little information is available on myoblast and fibroblast proliferation. Therefore, the purposes of this study were to establish a prudent protocol for myoblast cultures by comparing a variety of culturing procedures used in previous research and to quantitate myoblast proliferation and fusion under different culture conditions. In addition, the growth status of myoblasts and fibroblasts was investigated. Results indicate that the requirements for an ideal myoblast culture should include a combined enzyme of 0.25% trypsin and 0.2% collagenase type IV (1:1), a preplating time of approximately 15-20 minutes, and a seeding density at 1 x 10(5) cells/ml. Furthermore, the mouse sample should be those of newborns. A better proliferative capacity of myoblasts was noted in an incubator of 10% CO2, coupled with Dulbecco's MEM plus 15% fetal calf serum. The doubling times of myoblasts were shorter than those of fibroblasts, and myoblast number reached its highest at 4 and 5 days. The findings of this study are valuable in understanding the growth status of myoblasts and fibroblasts in primary cultures. Moreover, the establishment of requirements for a good growth of myoblast cultures will facilitate myoblast transfer therapy.
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PMID:Primary culture of mouse myoblasts. 762 15

Malignant glioma is a local invasive tumor in the central nervous system. The mRNA expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was examined in surgical specimens of three brain tissues, two astrocytomas, four anaplastic astrocytomas and eleven glioblastomas, including recurrent one anaplastic astrocytoma and two glioblastomas. In the control brain tissues, mRNA expression was high for TIMP-2, low for gelatinase A and TIMP-1, and undetectable for gelatinase B, interstitial collagenase, stromelysin and matrilysin. Gelatinase B and TIMP-1 were concomitantly overexpressed in primary glioblastomas. In addition, the average expression level of gelatinase A increased 3.0 fold in astrocytomas and anaplastic astrocytomas and 6.0 fold in glioblastomas, compared to the brain tissues. Matrilysin was induced variably in more than half of the primary glioblastomas, and interstitial collagenase was slightly induced in some primary and recurrent glioblastomas. Stromelysin was characteristically not expressed in any gliomas, and the expression level of TIMP-2 did not significantly change in the gliomas. These results suggest that the concomitant increased expression of gelatinase A, gelatinase B and occasional matrilysin genes is associated with the malignancy of gliomas and accompanied by the increased expression of TIMP-1 gene.
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PMID:[Increased expression of gelatinases A and B, matrilysin and TIMP-1 genes in human malignant gliomas ]. 763 25


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