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)

Diarylheptanoids are known to have anti-inflammatory and anti-atherosclerotic activities in various cell types, including macrophages. 5- O-Methylhirsutanonol (5-MH) isolated from the leaves of Alnus japonica Steud exhibited the antioxidant activities on Cu (2+)- and AAPH-mediated low-density lipoprotein (LDL) oxidation in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. In the main study, we examined anti-inflammatory activities of 5- O-methylhirsutanonol (5-MH) on nuclear factor kappaB (NF-kappaB)-dependent nitric oxide (NO) production and expression of inducible nitric oxide synthease (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. 5-MH inhibited NO production with an IC 50 value of 14.5 microM and expression of both iNOS protein and iNOS mRNA in a parallel dose-response manner. Then, expression of inflammation-associated genes, such as TNF-alpha, COX-2, and IL-1beta, was suppressed by 5-MH, as determined by reverse transcriptase polymerase chain reaction analysis. Moreover, 5-MH attenuated NF-kappaB activation by inhibition of hyperphosphorylation of IkappaB-alpha and its subsequent proteolytic degradation and p65 nuclear translocation, as well as preventing DNA-binding ability. In addition, 5-MH suppressed the mRNA expression of the gene reactive oxygen species (ROS) concerned in the regulation of NF-kappaB signaling.
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PMID:Effect of 5-O-Methylhirsutanonol on nuclear factor-kappaB-dependent production of NO and expression of iNOS in lipopolysaccharide-induced RAW264.7 cells. 1806 95

To identify positive or negative factors for HIV-1 infectivity, clones from the U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but differ in HIV-1 susceptibility, were compared. In contrast to HIV-1 permissive clone 10 (plus), nonpermissive clone 17 (minus) was adherent to coverslips coated with chemokines, was phagocytic, killed bacteria, and expressed human leukocyte elastase (HLE) in a granule-like compartment (HLEG) that was never detected at the cell surface (HLECS). In contrast to the minus clone, the plus clone expressed HLE on the cell surface and was adherent to coverslips coated with the HLECS ligands alpha1proteinase inhibitor (alpha1PI, alpha1antitrypsin) and the HIV-1 fusion peptide. The phosphorylation status of several important signaling proteins was studied at the single cell level. Tumor suppressor p53, NF-kappaB p65, and Akt were constitutively phosphorylated in the plus clone, but not in the minus clone. Surprisingly, both alpha1PI and LPS induced phosphorylation of NF-kappaB p65 Ser-536 in both clones, but induced dephosphorylation of Ser-529 in the plus clone only. HIV-1 permissivity was conferred to the minus clone in a manner that required stimulation by both alpha1PI and LPS and was coincident to NF-kappaB p65 phosphorylation/dephosphorylation events as well as translocation of HLE to the cell surface. Even when stimulated, the minus clone exhibited greater reverse transcriptase activity, but less p24, than the plus clone. Results presented suggest that HIV-1 uptake and production efficiency are influenced by signaling profiles, receptor distribution, and the phagocytic capacity specific to the stage of differentiation of the CD4+ target cell.
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PMID:NF-kappaB signaling, elastase localization, and phagocytosis differ in HIV-1 permissive and nonpermissive U937 clones. 1809 51

Oral squamous cell carcinoma (SCC) has a striking tendency to invade to bone. The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively secreted by osteoblasts and plays a key role in homing of hematopoietic cells to the bone marrow. Interleukin (IL)-6 plays an important role in osteoclastogenesis. Herein, we found that SDF-1 alpha increased the secretion of IL-6 in cultured human SCC cells, as shown by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. SDF-1 alpha also increased the surface expression of chemokine receptor 4 (CXCR4) in SCC cells. CXCR4-neutralizing antibody, CXCR4-specific inhibitor (AMD3100) or small interfering RNA against CXCR4 inhibited SDF-1 alpha-induced increase IL-6 production. The transcriptional regulation of IL-6 by SDF-1 alpha was mediated by phosphorylation of extracellular signal-regulated kinases (ERKs) and activation of the nuclear factor-kappa B (NF-kappaB) components p65 and p50. The binding of p65 and p50 to the NF-kappaB element on the IL-6 promoter was enhanced by SDF-1 alpha. In addition, IL-6 antibody antagonized the SCC-conditioned medium-increased osteoclastogenesis. These results suggested that SDF-1 alpha from osteoblasts could induce release of IL-6 in human SCC cells via activation of CXCR4, ERK and NF-kappaB pathway and thereby promote osteoclastogenesis.
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PMID:Bone-derived SDF-1 stimulates IL-6 release via CXCR4, ERK and NF-kappaB pathways and promotes osteoclastogenesis in human oral cancer cells. 1831 89

Diabetic patients have increased susceptibility to infection, which may be related to impaired inflammatory response observed in experimental models of diabetes, and restored by insulin treatment. The goal of this study was to investigate whether insulin regulates transcription of cytokines and intercellular adhesion molecule 1 (ICAM-1) via nuclear factor-kappaB (NF-kappaB) signaling pathway in Escherichia coli LPS-induced lung inflammation. Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and controls were instilled intratracheally with saline containing LPS (750 microg/0.4 mL) or saline only. Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU, s.c.) 2 h before LPS. Analyses performed 6 h after LPS included: (a) lung and mesenteric lymph node IL-1 beta, TNF-alpha, IL-10, and ICAM-1 messenger RNA (mRNA) were quantified by real-time reverse transcriptase-polymerase chain reaction; (b) number of neutrophils in the bronchoalveolar lavage (BAL) fluid, and concentrations of IL-1 beta, TNF-alpha, and IL-10 in the BAL were determined by the enzyme-linked immunosorbent assay; and (c) activation of NF-kappaB p65 subunit and phosphorylation of I-kappaB alpha were quantified by Western blot analysis. Relative to controls, diabetic rats exhibited a reduction in lung and mesenteric lymph node IL-1 beta (40%), TNF-alpha (approximately 30%), and IL-10 (approximately 40%) mRNA levels and reduced concentrations of IL-1 beta (52%), TNF-alpha (62%), IL-10 (43%), and neutrophil counts (72%) in the BAL. Activation of NF-kappaB p65 subunit and phosphorylation of I-kappaB alpha were almost suppressed in diabetic rats. Treatment of diabetic rats with insulin completely restored mRNA and protein levels of these cytokines and potentiated lung ICAM-1 mRNA levels (30%) and number of neutrophils (72%) in the BAL. Activation of NF-kappaB p65 subunit and phosphorylation of I-kappaB alpha were partially restored by insulin treatment. In conclusion, data presented suggest that insulin regulates transcription of proinflammatory (IL-1 beta, TNF-alpha) and anti-inflammatory (IL-10) cytokines, and expression of ICAM-1 via the NF-kappaB signaling pathway.
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PMID:Insulin regulates cytokines and intercellular adhesion molecule-1 gene expression through nuclear factor-kappaB activation in LPS-induced acute lung injury in rats. 1879 99

The cytokine tumor necrosis factor alpha (TNFalpha) is a key factor in several inflammatory diseases and its levels increase in response to a variety of internal or external stimuli. The regulation of the TNFalpha promoter is mediated by several transcription factors including the nuclear factor kappa B protein (NF-kappaB). This study examines the role of NF-kappaB in the regulation of TNFalpha production by morphine in microglia. Using reverse transcriptase polymerase chain reaction, we demonstrated the presence of morphine receptors in these cells. We next demonstrated the ability of morphine to promote TNFalpha production and secretion by these cells using a cytokine array assay. Transient transfection experiments led to the identification of the region located between nucleotides -751 and -615 within the TNFalpha promoter as being responsive to morphine treatment. The DNA sequence of this region contains a motif indicative of a potential NF-kappaB binding site. The use of a small interfering RNA directed against p65, a subunit of NF-kappaB, demonstrated that TNFalpha induction by morphine is NF-kappaB-dependent. All of the effects of morphine were reversed by the morphine inhibitor, naloxone. These data provide important insights into the effects of morphine on microglia.
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PMID:TNF alpha production in morphine-treated human neural cells is NF-kappaB-dependent. 1902 60

Intimal hyperplasia is one of the major pathological processes in vein graft failure with diabetes mellitus. In this study, we tested the hypothesis that the suppressive effect of aminoguanidine on intimal hyperplasia is mediated by downregulated expression of advanced glycation end products (AGE) and its receptor (RAGE) in streptozotocin-induced diabetes. To induce intimal hyperplasia, autologous external jugular vein was grafted into the infrarenal abdominal aorta in 52 male Sprague-Dawley rats. In diabetic rats, distilled water with or without aminoguanidine was administrated, whereas nondiabetic rats were given distilled water alone. Vein grafts were harvested at 1 and 4 weeks after surgery for morphological analysis and semiquantitative reverse transcriptase polymerase chain reaction analysis for RAGE and nuclear factor kappaB (NF-kappaB) p65. Serum AGE level was determined by fluorospectrophotometry. Compared to nondiabetic rats, serum levels of AGE in diabetic rats administrated distilled water were significantly increased. The expression of RAGE and NF-kappaB p65, the ratio of intima to media area, and the percentage of proliferating cell nuclear antigen (PCNA)-positive cells were significantly increased in the vein graft. In diabetic rats treated with aminoguanidine, serum AGE level NF-kappaB p65 expression, the ratio of intima to media area, and the percentage of PCNA-positive cells in the vein graft were all significantly decreased. However, no difference in the expression of RAGE was found compared to the diabetic group given distilled water. Our data suggest that AGE-RAGE may play a key role in venous intimal hyperplasia in diabetes mellitus and aminoguanidine suppressed intimal hyperplasia by inhibiting this pathway.
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PMID:The role of RAGE in aminoguanidine-induced suppression of venous intimal hyperplasia in diabetic rats. 1911 Apr

Colostrum, a nutrient-rich fluid produced by female mammals immediately after giving birth, is loaded with several immune, growth, and tissue repair factors. However, it remains unknown whether bovine colostrum has anti-inflammatory effects on intestinal epithelial cells (IEC). In this study, we aimed to investigate the anti-inflammatory effects of colostrum on IEC and to elucidate its molecular mechanisms. Human colon cancer HT-29 cells were stimulated with interleukin (IL)-1beta with or without bovine colostrum. The effects of colostrum on nuclear factor kappaB (NF-kappaB) signaling in HT-29 cells were examined using real-time reverse transcriptase-polymerase chain reaction detect IL-8 and intracellar adhesion molecule-1 mRNA expression using a NF-kappaB-dependent reporter gene assay and an electrophoretic mobility shift assay. Furthermore, we assessed the expression levels of inhibitor protein of NF-kappaB-alpha, cyclooxygenase-2, and p65 proteins by Western blotting. Bovine colostrum significantly inhibited IL-1beta-induced IL-8 and intracellar adhesion molecule-1 mRNA expression. Moreover, it suppressed IL-1beta-induced NF-kappaB activation, including NF-kappaB dependent reporter gene expression in a dose-dependent manner. Finally, Western blotting revealed that colostrum decreased the cyclooxygenase-2 protein expression level, inhibited inhibitor protein of NF-kappaB-alpha degradation, and blocked translocation of p65 into the nucleus. These data demonstrated that bovine colostrum might protect against IEC inflammation by inhibiting the NF-kappaB pathway, suggesting colostrum has a therapeutic potential for intestinal inflammation.
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PMID:Bovine colostrum inhibits nuclear factor kappaB-mediated proinflammatory cytokine expression in intestinal epithelial cells. 1941 Sep 80

The up-regulation of ferritin heavy chain (FHC) is reported in six papillary and in four invasive urothelial tumours of the urinary bladder of cattle grazing on mountain pastures rich in bracken fern. All tumours contained sequence of bovine papillomavirus type-2 (BPV-2) as determined by polymerase chain reaction (PCR) analyses and validated by direct sequencing of the amplified products. The oncoprotein E5 was also detected in these tumours by immunoprecipitation and by immunofluorescence and laser scanning confocal microscopy. Expression of FHC was evaluated by western blot analysis, reverse transcriptase (RT) PCR, real-time RT-PCR and immunohistochemistry. The oligonucleotide sequence of the bovine ferritin amplicons was identical to that of human ferritin. Nuclear overexpression of p65, an important component of nuclear factor kappaB (NF-kappaB) transcription factors, was also observed. These findings suggest that FHC up-regulation may be mediated by activation of NF-kappaB and that in turn this may be related to the resistance of bovine papillomavirus type-2 (BPV-2) infected urothelial cells to apoptosis.
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PMID:Ferritin heavy chain (FHC) is up-regulated in papillomavirus-associated urothelial tumours of the urinary bladder in cattle. 1959 55

We sought to evaluate the molecular markers involved in breast tumorigenesis in a rat model that mimics many essential elements of human breast cancer. Female Sprague-Dawley rats were divided into two groups. Animals in group 1 were given a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) (20 mg/rat) dissolved in 1 ml of sesame oil by intragastric intubation. Group 2 animals received basal diet and served as control. We analyzed DMBA-induced changes in the expression of CYP isoforms (CYP1A1 and 1B1) involved in DMBA metabolism, markers of oxidative stress (4HNE, HEL, and 8-OHdG), cell survival and proliferation (PCNA, NF-kappaB-p50, NF-kappaB-p65, GST-P, and p53), apoptosis (Bcl-2, Bax, caspases, Apaf-1, cytochrome C, and Fas), invasion (uPA, MMP-2, MMP-9, TIMP-2, and RECK), and angiogenesis (VEGF, VEGF-R1, HIF-1alpha, and PLGF) by immunohistochemical localization, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The present study demonstrates increased carcinogen metabolism, oxidative stress, cell proliferation, together with apoptosis evasion, invasion, metastasis, and neovascularization that may confer a selective growth advantage to DMBA-induced mammary tumors. Aberrant expression of multiple molecules in key signaling pathways in Sprague-Dawley rat mammary tumors renders this model as an important tool for monitoring carcinogenic progression and chemointervention.
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PMID:Evaluation of molecular markers in a rat model of mammary carcinogenesis. 1972 28

We have previously identified a neuroprotective effect associated with empty (E1(-), E3(-), E4(-)) adenovirus vector delivery in a model of light-induced, photoreceptor cell death. In this study, we further characterize this protective effect in light-injured retina and investigate its molecular basis. Dark-adapted BALB/c mice, aged 6-8 weeks, were exposed to standardized, intense fluorescent light for 96 or 144 h. Prior to dark adaptation, all mice received intravitreous injection of 1 x 10(9) particles of an empty (E1(-), E3(-), E4(-)) adenovirus vector in one eye and vehicle in the other. Following light challenge of 96 or 144 h, histopathological analysis and quantitative photoreceptor cell counts were conducted. Semiquantitative assessment of messenger ribonucleic acid (mRNA) for the apoptosis related genes: p50, p65, IkBa, caspase-1, caspase-3, Bad, c-Jun, Bax, Bak, Bcl-2, c-Fos, and p53 using quantitative reverse transcriptase polymerase chain reaction was performed on eyes following 12 h of light exposure. Following 96 h of light exposure, the photoreceptor cell density for E1(-), E3(-), E4(-) adenovirus vector and vehicle-injected eyes were 87.5 +/- 9.5 and 79.3 +/- 10.1, respectively, (p = 0.79). After 144 h of light exposure, the photoreceptor cell density was preserved in vector-injected eyes as compared to vehicle treated eyes, 68.9 +/- 10.0 and 49.2 +/- 4.6, respectively (p = 0.016). Relative mRNA levels of c-Fos and c-Jun at 12-h light exposure after injection differed significantly between vector- and vehicle-injected eyes (p = 0.036, 0.016, respectively). The expression of the other apoptosis-related genes evaluated was not significantly affected. This study investigates the molecular basis of photoreceptor neuroprotective pathway induction associated with E1(-), E3(-), E4(-) adenovirus vectors. The results indicate that empty adenovirus vectors protect photoreceptors from light-induced degeneration by the modulation of apoptotic pathways. Gene expression changes suggest that the suppression of c-Fos and c-Jun upregulation contributes significantly to the neuroprotective effect. Understanding the molecular basis of the neuroprotective pathway induction in photoreceptors is critical to the development of novel therapies for retinal degenerations.
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PMID:An empty E1, E3, E4 adenovirus vector protects photoreceptors from light-induced degeneration. 2007 33


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