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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metalloproteinases (MMPs) are proteolytic enzymes that function in the extracellular matrix to degrade connective tissues. While it is clear that exercise-induced injury in skeletal muscle promotes increased expression of MMPs, the relationship between exercise intensity and expression of MMPs in muscles is unknown. These experiments tested the hypothesis that exercise-induced expression of matrix metalloproteinases (MMP-2 and MMP-9) is dose-dependent such that high-intensity endurance exercise increases MMP expression whereas low-intensity endurance exercise will not promote MMP expression in skeletal muscles. Female rats (4 months old) completed 2 weeks of treadmill running at either low (18 m min(-1); approximately 50% maximum oxygen consumption rate ) or high intensity (32 m min(-1); approximately 70% ; up to 50 min day(-1)). Non-running, sedentary animals served as controls. Muscle mRNA and protein levels of MMP-2 and MMP-9 were assessed in gastrocnemius, quadriceps and soleus muscles by reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Results indicate that exercise did not alter MMP-9 in any of these skeletal muscles. Further, our data reveal that low-intensity exercise did not alter the expression of MMP-2 in any of the muscles investigated. In contrast, high-intensity exercise increased both mRNA and protein levels of MMP-2 in skeletal muscles containing a high percentage of fast type II fibres (i.e. gastronemius and superficial quadriceps). These results support the hypothesis that high-intensity exercise is required to promote the expression of MMP-2 in skeletal muscles and that the influence of exercise on MMP-2 expression is dominant in muscles containing a high percentage of fast fibres.
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PMID:High intensity exercise increases expression of matrix metalloproteinases in fast skeletal muscle fibres. 1583 56

The combination of cyclosporine (CSA) and rapamycin (RAPA) is a potent and commonly used approach to immunosuppression following solid-organ transplantation. By applying varying doses of CSA and RAPA to the rat salt-depleted model, we aimed to find a dose combination that favored antiproliferation/antifibrosis rather than toxicity. Male Sprague-Dawley rats (350 to 500 g) were salt-depleted for 7 days prior to commencing CSA and RAPA treatment. Serum creatinine and urinary protein/creatinine ratios were measured. Fibrosis was estimated with Sirius red staining of extracellular collagen. mRNA expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was assessed with reverse transcriptase PCR. A rise in serum creatinine at 7 and 28 days was observed for CSA 15 mg/kg/d (P = .002) but not CSA 7.5 mg (P = .06) or RAPA 1 mg (P = .69) compared to controls. Twenty-four-hour urinary protein excretion was unchanged compared to controls for all drug doses and combinations. Of the dose combinations, CSA 7.5 mg/d + RAPA 0.5 mg/d produced the lowest serum creatinine for all time points, and inhibited profibrotic TIMP-1 (P = .017), while increasing antifibrotic MMP-2 (P = .009) mRNA expression, compared to CSA treatment alone. Expression of TGF-beta and collagen III was unaltered between groups. CSA treatment produced molecular and biochemical changes indicating renal damage. Addition of RAPA can attenuate this damage, but only with a dose reduction of both agents. The most favorable results were for the dose combination CSA 7.5 mg/kg/d plus RAPA 0.5 mg/kg/d.
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PMID:Cyclosporine and rapamycin act in a synergistic and dose-dependent manner in a model of immunosuppressant-induced kidney damage. 1584 49

Although ischemia remains the leading cause of acute renal failure in humans, there is little information on the expression and activities of gelatinases of kidney glomeruli during ischemia-reperfusion injury. In this study, we used a unilateral ischemia-reperfusion model to investigate the activity and expression of gelatinases in glomeruli during acute ischemia. Unilateral ischemia was induced in rats by vascular clamping (30 min) followed by reperfusion (60 min) and isolation of glomeruli. The activity and expression of gelatinase proteins were determined by gelatin zymography and Western blotting. Gelatinase mRNA levels were evaluated by reverse transcriptase-PCR. Ischemia and reperfusion increased serum creatinine levels, hallmark of acute renal failure. Ischemia induced mRNA and protein MMP-2 expression. There was strong stimulation of MMP-9 mRNA, both forms of dimeric MMP-9, and active monomeric MMP-9. In contrast to TIMP-1 decreasing, TIMP-2 protein and mRNA increased during ischemia. During reperfusion, there was a gradual reversal of the MMP-2 and MMP-9 levels and a strong inhibition of TIMP-1 and TIMP-2 at the protein and mRNA levels. Endocytic receptor LRP was increased during ischemia and returned to normal during reperfusion. Expression of MMP-9 docking receptor CD-44 was increased during reperfusion. Finally, ZO-1, an in vivo MMP-9 substrate, was degraded during ischemia, revealing that MMP-9 upregulated during ischemia was functional. Our data suggest that stimulation of gelatinase activity during ischemia could contribute to glomeruli injury, providing new therapeutic targets for acute renal failure in humans. In contrast, elevated monomeric MMP-9 activity due to TIMP-1 decrease during reperfusion may participate to glomerular recovery.
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PMID:Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli. 1587 Aug 43

An immortalized human prostate stromal cell line (PS30) was previously established using recombinant retrovirus encoding human papillomavirus 16 gene products. In this study, we further characterize this stromal cell line for its potential use in a stromal-epithelial coculture model for prostate cancer prevention. Using reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunocytochemistry, we examined expression of androgen receptor (AR), vitamin D receptor (VDR), prostate-specific antigen (PSA), transforming growth factor-beta (TGF-beta), and insulin-like growth factors (IGF) families and their receptors, metalloproteinases (MMP) MMP-2 and MMP-9, as well as the cells' ability to respond to the synthetic androgen R1881. The PS30 stromal cells do not express PSA, confirming their stromal origin. They are positive for both AR messenger ribonucleic acid (mRNA) and protein; however, they do not respond to growth stimulation by the synthetic androgen R1881. The PS30 cells express mRNA for VDR, TGF-betas, IGFs and their receptors, as well as the MMPs. Moreover, they produce significant amounts of TGF-beta1, TGF-beta2, IGFBP-3, and MMP-2 proteins. Our observations confirm the use of PS30 for the study of stromal-epithelial interactions in the modulation of prostate carcinogenesis.
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PMID:Characteristics of a human prostate stromal cell line related to its use in a stromal-epithelial coculture model for the study of cancer chemoprevention. 1615 46

Caffeic acid phenethyl ester (CAPE) derived from honeybee propolis has been used as a folk medicine. Recent study also revealed that CAPE has several biological activities including antioxidation, anti-inflammation and inhibition of tumor growth. The present study investigated the effect of CAPE on tumor invasion and metastasis by determining the regulation of matrix metalloproteinases (MMPs). Matrix metalloproteinases, which are zinc-dependent proteolytic enzymes, play a pivotal role in tumor metastasis by cleavage of extracellular matrix (ECM) as well as nonmatrix substrates. On this line, we examined the influence of CAPE on the gene expression of MMPs (MMP-2, MMP-9, MT1-MMP), tissue inhibitor of metalloproteinase-2 (TIMP-2) and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent decreases in MMP and TIMP-2 mRNA levels were observed in CAPE-treated HT1080 human fibrosarcoma cells as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Gelatin zymography analysis also exhibited a significant down-regulation of MMP-2 and MMP-9 expression in HT1080 cells treated with CAPE compared to controls. In addition, CAPE inhibited the activated MMP-2 activity as well as invasion, motility, cell migration and colony formation of tumor cells. These data therefore provide direct evidence for the role of CAPE as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant cells.
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PMID:Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. 1621 27

Matrix metalloproteinases (MMPs), zinc-dependent proteolytic enzymes, play a pivotal role in tumor metastasis by cleavage of extracellular matrix as well as non-matrix substrates. In this study, we examined the influence of DA-125, a new anthracyclin analog, on the gene expression of MMPs (MMP-2, MMP-9 and MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent decreases of MMPs and TIMPs mRNA levels were observed in DA-125-treated HT1080 human fibrosarcoma cells detected by reverse transcriptase-polymerase chain reaction. Gelatin zymography analysis also showed a significant down-regulation of MMP-2 and MMP-9 expression in HT1080 cells treated with DA-125 compared to controls. In addition, DA-125 inhibited the invasion, motility and cell migration, and colony formation of tumor cells. These data, therefore, provide direct evidence for the role of DA-125 as a potential cancer chemotherapeutic agent, which can markedly inhibit the invasive capacity of malignant cells. Further, to clarify the transcriptional regulatory pathway, we primarily investigated the role of nuclear factor-kappaB (NF-kappaB) in the expression of MMPs by DA-125 in HT1080 cells. Electrophoretic mobility shift assay demonstrated that DA-125 modulates the binding activity of NF-kappaB. Using the luciferase reporter gene assay, a dose-dependent down-regulation of NF-kappaB-mediated luciferase expression was also observed. These results suggest that DA-125 down-regulates MMPs expression in HT1080 cells through the NF-kappaB-mediated pathway.
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PMID:Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix metalloproteinases. 1627 Dec 63

In our previous study, a synthetic benz[f]indole-4,9-dione analog, 2-amino-3-ethoxycarbonyl-N-methylbenz[f]indole-4,9-dione (SME-6), exhibited a potential anti-tumor activity. We, in this study, further explored the anti-metastatic and anti-invasive effect of SME-6 by determining the regulation of matrix metalloproteinases (MMPs). MMPs, zinc-dependent proteolytic enzymes, play a pivotal role in tumor metastasis by cleavage of extracellular matrix as well as non-matrix substrates. On this line, we examined the influence of SME-6 on the expressions of MMP-2, -9, membrane type 1-MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-1, -2), and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent suppressions of MMPs and TIMP-2 mRNA levels were observed in SME-6-treated HT1080 human fibrosarcoma cells detected by reverse transcriptase-polymerase chain reaction. TIMP-1 mRNA level, however, was induced in a dose-dependent manner. Gelatin zymographic analysis also exhibited a significant down-regulation of MMP-2 and -9 expression in HT1080 cells treated with SME-6 compared to controls. Furthermore, SME-6 inhibited the invasion, motility, and migration of tumor cells. Taken together, these data provide a possible role of SME-6 as a potential antitumor agent with the markedly inhibition of the metastatic and invasive capacity of malignant cells.
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PMID:Inhibitory effects of a benz[f]indole-4,9-dione analog on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. 1630 69

Matrix metalloproteinases (MMPs), a class of enzymes responsible for the degradation of extracellular matrix proteins, play important roles in inflammatory and immune responses. In skin, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are normally inactive but can be expressed during tissue injury. Both degrade collagen IV and other critical components of the basement membrane zone that separates the epidermis from the dermis. The expression of MMP-2 and -9 was studied in sulfur mustard (SM)-exposed ear skin from mice to determine their role in tissue vesicant injury. Punch biopsies of mouse ears were collected between 6 and 168 h after exposure to 97.5 mM (0.08 mg) SM diluted in CH(2)Cl(2). They were examined histologically and assayed for MMP-2 and -9 expression by gelatinase activity assays, real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. A time-related increase in overall gelatinase activity was observed in SM-treated ears. At 168 h after SM exposure, the relative levels of MMP-9 mRNA were increased 27-fold and MMP-9 protein 9-fold when compared with the control (CH(2)Cl(2) treated) ears. In contrast, there were no observable increases in the MMP-2 mRNA or protein levels between treated and control ears. These observations suggest the differential expression of MMP-2 and -9 during the cutaneous response to SM injury and suggest a role for MMP-9 in SM-induced injury.
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PMID:Preferential expression of matrix metalloproteinase-9 in mouse skin after sulfur mustard exposure. 1648 79

Metalloproteinases (MMPs) are proteolytic enzymes that function in the extracellular matrix to degrade connective tissues. While it is clear that certain induced skeletal muscle pathologies promote increased expression of MMP-2 and heat shock protein- 72 (HSP-72), the relationship between muscle disuse and expression of MMP-2 and HSP-72 in muscles is unknown. These experiments tested the hypothesis that knee immobilization induced expression of MMP-2 and HSP-72 is disuse-dependent in a way that short-term joint immobilization increases HSP-72 expression, whereas long-term joint immobilization increases MMP-2 expression in skeletal muscles. Male rats (8 months old) completed 1, 2, 3, and 4 weeks of knee joint immobilization. Muscle mRNA and protein levels of MMP-2 and HSP-72 were assessed in Gastrocnemius (Gast), Superficial and Deep Quadriceps, and Soleus (Sol) muscles by reverse transcriptase-polymerase chain reaction and western blotting, respectively. Results reveal that during the first two weeks of immobilization there is increased protein levels of HSP-72 and expression of mRNA of HSP-72 mainly in slow twitch muscle fibers. However, 3 and 4 weeks of joint immobilization increased both mRNA and protein levels of MMP-2 in skeletal muscles containing a high percentage of fast type II fibers (i.e., Gast and superficial quadriceps). These results support the hypothesis that different periods of muscle disuse induced different proteins expression, and that the influence of joint immobilization on the expression of HSP-72 in the short-term, and MMP-2 in the long ran is associated to fiber types.
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PMID:Expression of matrix metalloproteinase 2 and heat shock protein-72 in immobilized muscle in rats. 1667 93

Immune response is critically involved in determining the course of viral myocarditis and immunomodulation. Different cytokines may have either deleterious or protective effects. Following acute Coxsackievirus B3 infection, intramyocardial inflammation is associated with altered myocardial matrix metalloproteinase (MMP) expression and left ventricular dysfunction. In this study, we evaluated the effect of exogenous interleukin-4 treatment on myocardial inflammation, MMPs and left ventricular function in Coxsackievirus B3-induced acute murine myocarditis. Eight-week-old inbred male BALB/c (H-2d) mice (The Jackson Laboratory, Bar Harbor, Maine, USA) were used. Myocardial inflammation was measured by immunohistochemical detection of CD3(+)-, CD8a(+)-T-lymphocytes, and CD11b+ macrophages. In situ hybridization was used to detect enteroviral genome in the myocardium. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was employed to detect cytokine and MMP mRNA. MMP activity was quantified by zymography analysis. Detection of myocytolysis was performed by Luxol fast blue staining. In the early acute phase, in comparison to infected mice without treatment, interleukin-4 administration (200 ng daily) reduced intramyocardial inflammation (CD3+ lymphocytes: 55.3+/-7.0 vs. 72.1+/-13.7 cells/mm2, P < 0.05; CD8a+ lymphocytes: 31.7+/-3.6 vs. 64.2+/-7.7 cells/mm2, P < 0.05; CD11b+ macrophages: 5.1+/-2.3 vs. 13.2+/-2.5 cells/mm2, P < 0.05). It also down-regulated interleukin-2 (IL) (1.7-fold, P < 0.001) but increased transforming growth factor-beta1 (TGF) (1.5-fold, P < 0.001) and IL-4 (1.4-fold, P < 0.001). IL-4 suppressed MMP-2/-3/-9 transcription and activity. These biochemical alterations were accompanied by a significant improvement of left ventricular function as assessed by Milar tip catheter (left ventricular endsystolic pressure, 1.3-fold, P < 0.01; dP/dt max, 1.5-fold, P < 0.01). Immunomodulation by exogenous IL-4 treatment may lead to an anti-inflammatory effect with the inhibition of Th1 cell phenotypic response, which may further mediate the down-regulation of MMPs. A significant suppression of MMPs may mainly contribute to an improvement of left ventricular dysfunction in acute murine CVB3-induced myocarditis.
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PMID:Immunomodulation by interleukin-4 suppresses matrix metalloproteinases and improves cardiac function in murine myocarditis. 1711 76


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