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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our objective was to examine the role of an exogenous nitric oxide (NO) donor, DETA-NONOate (DETA), on matrix metalloproteinase (MMP)-9, MMP-2, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 expression and activity in interleukin (IL)-1beta-induced rat aortic smooth muscle cells (RA-SMCs) and rat aortic explants (RAEs). RA-SMCs were incubated with IL-1beta (2 ng/ml), an inflammatory cytokine known to induce MMP-9 expression, and increasing concentrations of DETA (0, 1.0, 10, 100 microM; n = 3/group) for 48 hr. RAEs were incubated with IL-1beta (2 ng/mL) and increasing concentrations of DETA (0, 5.0, 50, 100, and 500 microM; n = 3/group) for 48 hr. Media were collected and assayed for NO(x) by the Griess reaction and MMP-9 activity by zymography. Messenger RNA (mRNA) was extracted from cells and analyzed for MMP-9, MMP-2, and TIMP-1 expression levels by quantitative real-time reverse-transcriptase polymerase chain reaction. All statistical analyses were performed by analysis of variance. In RA-SMCs and RAEs, DETA administration resulted in a dose-dependent increase in media NOx concentration (RA-SCM p < 0.01, RAE p < 0.01) and a concurrent decrease in both MMP-9 expression (RASMC p = 0.01, RAE p = 0.01) and activity (RASMC p = 0.04, RAE p = 0.006). There were no significant differences seen in MMP-2 and TIMP-1 expression or activity in response to DETA exposure. DETA decreased IL-1beta-induced MMP-9 expression and activity in both RA-SMCs and RAEs in a dose-dependent fashion. In addition, DETA administration had no effect on MMP-2 or TIMP-1 expression or activity in vitro. These data suggest that NO donors may be beneficial in decreasing MMP-9 levels and might serve to inhibit MMP-9-dependent vessel wall remodeling seen during abdominal aortic aneurysm formation.
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PMID:The nitric oxide donor DETA-NONOate decreases matrix metalloproteinase-9 expression and activity in rat aortic smooth muscle and abdominal aortic explants. 1637 39

Cruciferous vegetables contain a series of relatively unique secondary metabolites of amino acids, called glucosinolates. Sinigrin, the predominant aliphatic glucosinolate in cruciferous vegetables, is hydrolyzed to yield allyl isothiocyanate (AITC), which, after absorption and metabolism in humans, is excreted in the urine as an N-acetylcysteine (NAC) conjugate. We have determined the inhibitory effects of AITC and its NAC conjugate on cell proliferation, the expression of matrix metalloproteinases (MMPs), adhesion, invasion, and migration in SK-Hep 1 human hepatoma cells. Our results demonstrate that AITC and NAC-AITC suppress SK-Hep 1 cell proliferation in a dose-dependent manner; by 25% and 30% for 10 microM AITC and 10 microM NAC-AITC, respectively. We examined the influence of AITC and NAC-AITC on the gene expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). Gelatin zymography also revealed a significant downregulation of MMP-2/-9 expression in SK-Hep1 cells treated with 0.1-5 microM AITC and NAC-AITC compared with controls. Reverse transcriptase polymerase chain reaction revealed dose-dependent decreases in MMP-2/-9 messenger RNA levels in both AITC-treated and NAC-AITC-treated cells. TIMP-1/-2 activities were unaffected by treatment with AITC or NAC-AITC in our experiments. NAC-AITC inhibited cancer cell adhesion and invasion much more potently than its parent compound. NAC-AITC at 5 microM caused excellent inhibition of cell migration for 48 hrs. These results demonstrate the potential of AITC and NAC-AITC as chemopreventive agents.
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PMID:Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in SK-Hep 1 human hepatoma cells. 1656 38

Dental pulp destruction is believed to be regulated, in part, by the matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Cytokines are believed to be important in the pathogenesis of pulpitis. This study examined the effects that TNF-alpha, IL-1beta, IL-6, and TGF-beta1 have on the collagen degradation mediated by pulp fibroblasts utilizing a cell-mediated collagen degradation assay. Reverse transcriptase-polymerase chain reaction, Western blot analyses, and zymography were utilized to examine multiple MMPs and TIMPs. The collagen degradation mediated by these cells was stimulated by these cytokines. TNF-alpha, IL-1beta, and IL-6 increased the mRNA and/or protein expression of MMP-1, MMP-2, and MMP-3. TGF-beta1 decreased MMP-1 mRNA expression, while only slightly affecting the MMP-2 and MMP-3 mRNA and/or protein. These cytokines did not affect the expression of TIMP-1 or TIMP-2. These results suggest that these cytokines affect pulp destruction, in part, by differentially regulating the MMPs and TIMPs.
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PMID:The effects of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and transforming growth factor-beta1 on pulp fibroblast mediated collagen degradation. 1693 28

The goal of articular cartilage tissue engineering is to provide cartilaginous constructs to replace abnormal cartilage. We have evaluated the chondroprogenitor clonal cell line RCJ3.1C5.18 (C5.18) as a model to guide the development of appropriate scaffolds for tissue engineering. Rapid degradation of fibrin hydrogels was observed after encapsulation of C5.18 cells. The enzymes responsible for this fibrin gel breakdown were characterized to control their activity and regulate gel stability. Western blotting, confirming zymography, revealed bands due to matrix metalloproteinases (MMP-2, MMP-3) that are secreted concomitantly with fibrin hydrogels breakdown. High plasmin activity was detected in conditioned media during hydrogel breakdown but not in the confluent cells before encapsulation. Reverse transcriptase polymerase chain reaction indicated the expression of MMP-2, -3, and -9 and plasminogen in the cells. MMP-9 was 100 times higher at day 1, whereas MMP-2 started to increase and reached its maximum level by day 7. Aprotinin, a known serine protease inhibitor, and galardin (GM6001), a potent MMP inhibitor, in combination or separately, prevented the breakdown of fibrin-C5.18 hydrogels, whereas only the combination of both promoted the accumulation of extracellular matrix. These findings suggest that plasmin and MMPs contribute independently to fibrin hydrogel breakdown, but that either enzyme can achieve extracellular matrix breakdown.
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PMID:Characterization and inhibition of fibrin hydrogel-degrading enzymes during development of tissue engineering scaffolds. 1751 6

Tumor invasion and immortality are the most unfavorable drawbacks after cancer treatment. In this study, we focus on determining the photodynamic modulation of the proteolytic enzymes, matrix metalloproteinases (MMP); and a core catalytic subunit of telomerase, the human telomerase reverse transcriptase (hTERT) in medulloblastoma (MED) cell line (TE-671). Hexvix (ALA-H) mediated photodynamic therapy (PDT) demonstrated greater efficacy than 5-aminolevulinic acid (5-ALA) in terms of drug uptake and anti-proliferative effect. Both MMP-2 and hTERT expression are down-regulated quantitatively using ELISA and reverse-transcriptase-PCR (RT-PCR) respectively at post-treatment for this cell line. The MMP-9 expression remains unchanged after treatment. Further, there is a statistically significant inhibition of cell migration at 24 h post-ALA-H-PDT at LD(50) (0.01 mM, 2 J cm(-2); p < 0.001) in MED TE-671 cells. Evidently, MMP-2 and hTERT mRNA expressions can be the targets for the photodynamic intervention on tumor cell migration and immortality. Hence, PDT may be an alternate cancer regime for medulloblastoma.
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PMID:Photodynamic effect in medulloblastoma: downregulation of matrix metalloproteinases and human telomerase reverse transcriptase expressions. 1816

We previously demonstrated that a high dose of tacrolimus (1 mumol/L) induced expression of matrix metalloproteinase (MMP) proteins in human cultured gingival fibroblasts, suggesting a molecular mechanism maintaining gingival collagen homeostasis in tacrolimus-treated patients. Herein we have analyzed whether the effect on collagen turnover might be influenced by a therapeutic tacrolimus dose. Human gingival fibroblasts were incubated for 72 hours with 10 nmol/L, 100 nmol/L, and 1 mumol/L tacrolimus, or left untreated (CT). Collagen type I and III (COL-I, COL-III), lysyl hydroxylase 2b (LH2b), MMP-1 and -2, tissue inhibitor of MMP-1 and transforming growth factor-beta1 (TGF-beta1) mRNA levels were assayed by reverse-transcriptase polymerase chain reaction, collagen protein levels by dot blot, and MMP activity by sodium dodecyl sulfate zymography. Tacrolimus did not affect COL-I, COL-III, or MMP gene expression, while LH2b and TGF-beta1 tended to be down-regulated after 1 mumol/L FK506. Conversely, protein levels of MMP-1 (P = NS) and MMP-2 (P < .05 vs CT, 10 nmol/L, 100 nmol/L) were up-regulated after 1 mumol/L tacrolimus. Our findings confirmed that a high dose of tacrolimus does not induce interstitial collagen overexpression by gingival fibroblasts and induces up-regulation of MMPs protein levels. Interestingly, at doses corresponding to whole blood trough levels, tacrolimus did not exert any evident effect on collagen turnover pathways, suggesting that tacrolimus is likely to not affect collagen homeostasis in the gingival connective tissue compartment of FK506-immunosuppressed subjects. This effect did not seem to be dose-dependent.
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PMID:A therapeutic dose of FK506 does not affect collagen turnover pathways in healthy human gingival fibroblasts. 1858 21

Morin--a bioflavonoid is a naturally available dietary agent believed to impede cancer promotion and progression. The present study was conducted to decipher, in vivo, the role of morin on the expression of matrix metalloproteinases, cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-kappaB)-p65 during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in Wistar albino rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that administration of DEN (200 mg/kg bodyweight in drinking water) to experimental animals caused inflammation of the liver due to up-regulation of NF-kappaB-p65 and COX-2. RT-PCR and immunoblot analysis also revealed that the oral supplementation of morin (500 ppm in diet) to DEN-induced hepatocellular carcinoma rats down-regulated the expression of COX-2 and NF-kappaB-p65, thereby preventing inflammation and angiogenesis mediated hepatocellular carcinogenesis. Further, immunohistological analysis for NF-kappaB-p65 nuclear localization confirms the above observations. Gelatin zymography was performed for matrix metalloproteinase MMP-2 and MMP-9 expression to confirm their role in angiogenesis in DEN induced hepatocellular carcinoma and its modulation by morin. Both MMP-2 and MMP-9 levels were found to be increased in DEN-induced animals when compared to control. MMP-2 and MMP-9 levels were down-regulated in morin post-treated animals when compared to DEN-induced animals favouring prevention of angiogenesis. In conclusion, our findings indicate that morin possessed anti-inflammatory and anti-cancer properties favouring suppression of DEN-induced hepatocellular carcinoma.
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PMID:Morin regulates the expression of NF-kappaB-p65, COX-2 and matrix metalloproteinases in diethylnitrosamine induced rat hepatocellular carcinoma. 1953 2

This study assessed the effects of microcystin-LR (MC-LR) exposure on matrix metalloproteinases (MMPs) expression and cancer cell migration. After male mice were orally administered with different concentrations of MC-LR for 270 d, histopathologic observation revealed an obvious hepatic lymphocyte infiltration or fatty degeneration. Immunohistochemical staining and enzyme-linked immunosorbent assay demonstrated that MC-LR treatment (even at 1 nM) caused up-regulated expressions of hepatic MMP-2/-9. Quantitative reverse-transcriptase PCR showed that the exposure to 80 nM MC-LR induced an increase of MMP-2/-9 mRNA levels by 1.0 and 1.9 fold. Breast cancer cells (MDA-MB-435s) were also cultured with MC-LR solutions and a wound healing assay demonstrated that MC-LR posed a time/dose-dependent stimulation effect on migration of the cancer cells. Gelatin electrophoresis and quantitative PCR showed significant increases in cellular MMP-2/-9 expressions after MC-LR exposure. This study indicated that chronic exposure to MC-LR could alter MMP-2/-9 expressions and stimulate cancer cell migration.
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PMID:Effects of microcystin-LR exposure on matrix metalloproteinase-2/-9 expression and cancer cell migration. 2208 28


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