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)

Overproduction of collagen (I) by activated hepatic stellate cells is a critical step in the development of liver fibrosis. It has been established that these cells express interleukin (IL)-6 and respond to this cytokine with an increase in alpha(I) collagen. Pentoxifylline, a methylxanthine derivate, has been reported to have antifibrotic properties, but the mechanism responsible for this effect is unknown. The aim of this study was to determine the effect of pentoxifylline on acetaldehyde-induced collagen production in a rat hepatic stellate cell line (CFSC-2G cells). Cells were treated with 100 microM acetaldehyde and 200 microM pentoxifyline for 3 h. IL-6 and alpha(I) collagen messenger RNA (mRNA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) assay. NFkappaB activation was determined by electrophoretic mobility shift assay. To corroborate NFkappaB participation in pentoxifylline effect, cells were pretreated with 10 microM TPCK, a NFkappaB inhibitor. IkappaBalpha was determined by Western blot. IL-6 expression decreased significantly in acetaldehyde-pentoxifylline-treated cells. Acetaldehyde-treated cells pretreated with an anti-IL-6 monoclonal antibody did not show any increase in alpha (I) collagen expression. Acetaldehyde-treated cells increased 1.48 times NFkappaB activation, whereas acetaldehyde-pentoxifylline-treated cells decreased NFkappaB activation to control values. TPCK pretreated acetaldehyde cells did not present NFkappaB activation. To corroborate NFkappaB participation in pentoxifylline effect, IkappaBalpha was determined. IkappaBalpha protein level decreased 50% in acetaldehyde-treated cells, while acetaldehyde-pentoxifylline-treated cells showed IkappaBalpha control cells value. The data suggest that acetaldehyde induced alpha(I) collagen and IL-6 expression via NFkappaB activation. Pentoxifylline prevents acetaldehyde-induced alpha(I) collagen and IL-6 expression by a mechanism dependent on IkappaBalpha degradation, which in turn blocks NFkappaB activation.
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PMID:Pentoxifylline downregulates alpha (I) collagen expression by the inhibition of Ikappabalpha degradation in liver stellate cells. 1795 19

Highly active antiretroviral therapy (HAART) is often associated with endothelial dysfunction and cardiovascular complications. In this study, we determined whether HIV non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) could increase endothelial permeability. Human coronary artery endothelial cells (HCAECs) were treated with EFV (1, 5 and 10 microg/ml) and endothelial permeability was determined by a transwell system with a fluorescence-labeled dextran tracer. HCAECs treated with EFV showed a significant increase of endothelial permeability in a concentration-dependent manner. With real time PCR analysis, EFV significantly reduced the mRNA levels of tight junction proteins claudin-1, occludin, zonula occluden-1 and junctional adhesion molecule-1 compared with controls (P<0.05). Protein levels of these tight junction molecules were also reduced substantially in the EFV-treated cells by western blot and flow cytometry analyses. In addition, EFV also increased superoxide anion production with dihydroethidium and cellular glutathione assays, while it decreased mitochondrial membrane potential with JC-staining. Antioxidants (ginkgolide B and MnTBAP) effectively blocked EFV-induced endothelial permeability and mitochondrial dysfunction. Furthermore, EFV increased the phosphorylation of MAPK JNK and IkappaBalpha, thereby increasing NFkappaB translocation to the nucleus. Chemical JNK inhibitor and dominant negative mutant JNK and IkappaBalpha adenoviruses effectively blocked the effects of EFV on HCAECs. Thus, EFV increases endothelial permeability which may be due to the decrease of tight junction proteins and the increase of superoxide anion. JNK and NFkappaB activation may be directly involved in the signal transduction pathway of EFV action in HCAECs.
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PMID:Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells. 1967 47

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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