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)

Extracellular superoxide dismutase (SOD(EX)), an antioxidant enzyme, was found to be present in the testis at a relatively high concentration versus other organs. In a more detailed survey of several rat tissues and cells by reverse transcriptase-polymerase chain reaction, it was shown that germ cells expressed approximately one-third that of Sertoli cells, suggesting both cell types are equipped with the machinery needed to defend themselves from radical-induced damage. When we used an in vitro model in which germ cells were co-cultured with Sertoli cells at a Sertoli:germ cell ratio of 1:1, we failed to detect any changes in the mRNA level of SOD(EX). However, the addition of increasing concentrations of germ cell secretory proteins into Sertoli cell cultures resulted in a decrease in Sertoli cell SOD(EX) expression, illustrating that germ cells can indeed regulate Sertoli cell SOD(EX). On the other hand, Sertoli cell SOD(EX) expression was stimulated when human recombinant interleukin-1alpha (IL-1alpha), a germ cell product, was included into Sertoli cells in vitro. These results, taken collectively, suggest SOD(EX) is an important antioxidant molecule in the testis that is under germ cell regulation.
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PMID:Antioxidant superoxide dismutase - a review: its function, regulation in the testis, and role in male fertility. 1202 Jul 84

Injury to motor neurons associated with mutant Cu,Zn-superoxide dismutase (SOD1)-related familial amyotrophic lateral sclerosis (FALS) results from a toxic gain-of-function of the enzyme. The mechanisms by which alterations to SOD1 elicit neuronal death remain uncertain despite intensive research effort. Analysis of the cellular proteins that are differentially expressed in the presence of mutant SOD1 represents a novel approach to investigate further this toxic gain-of-function. By using the motor neuron-like cell line NSC34 stably transfected with wild-type, G93A, or G37R mutant human SOD1, we investigated the effects of mutant human SOD1 on protein expression using proteomic approaches. Seven up-regulated proteins were identified as argininosuccinate synthase, argininosuccinate lyase, neuronal nitric-oxide synthase, RNA-binding motif protein 3, peroxiredoxin I, proteasome subunit beta 5 (X), and glutathione S-transferase (GST) Alpha 2. Seven down-regulated proteins were identified as GST Mu 1, GST Mu 2, GST Mu 5, a hypothetical GST Mu, GST Pi B, leukotriene B(4) 12-hydroxydehydrogenase, and proteasome subunit beta5i (LMP7). GST assays demonstrated a significant reduction in the total GST activity of cells expressing mutant human SOD1. Proteasome assays demonstrated significant reductions in chymotrypsin-like, trypsin-like, and post-glutamylhydrolase proteasome activities. Laser capture microdissection of spinal cord motor neurons from human FALS cases, in conjunction with reverse transcriptase-PCR, demonstrated decreased levels of mRNA encoding GST Mu 1, leukotriene B(4) 12-hydroxydehydrogenase, and LMP7. These combined approaches provide further evidence for involvement of alterations in antioxidant defenses, proteasome function, and nitric oxide metabolism in the pathophysiology of FALS.
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PMID:Analysis of the cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, and nitric oxide synthetic pathways. 1247 80

The present study determined whether gene transfer of human copper/zinc superoxide dismutase-1 (Cu/Zn SOD-1) prevented the autoregulatory impairment of CBF induced by subarachnoid hemorrhage (SAH). After application of recombinant adenovirus (100 microL of 1 x 10(10) pfu/mL, intracisternally) encoding human Cu/Zn SOD-1 3 days before experiments, Cu/Zn SOD-1 activity significantly increased in association with increase in Cu/Zn SOD-1 mRNA and protein expression in the cerebral vasculature of both sham-operated and SAH rats as determined by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry, and SAH-induced increase in superoxide anion was markedly reduced in accordance with increased nitric oxide production. In line with these findings, rats that received human Cu/Zn SOD-1 therapy showed the prominent restoration of blunted vasodilation of the pial artery in response to calcitonin gene-related peptide and levcromakalim, and the recovery of impaired autoregulatory vasodilation in response to acute hypotension, thereby leading to significant restoration of CBF autoregulation. These results provide a rational basis for application of Cu/Zn SOD-1 gene therapy for protection of the impairment of autoregulatory CBF during the acute stage of SAH.
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PMID:Prevention of impairment of cerebral blood flow autoregulation during acute stage of subarachnoid hemorrhage by gene transfer of Cu/Zn SOD-1 to cerebral vessels. 1250 96

To study the protective effects of the antioxidant superoxide dismutase (SOD) against platelet-activating factor (PAF)-induced endothelial permeability. Endothelial cells (ECs) were isolated from human umbilical veins from normal pregnancies. The first passage (P1) ECs were grown in polycarbonate transwell filters. Confluent ECs were incubated with PAF at concentrations of 2, 5, and 10 microgram/mL for 2 hours or pretreated with superoxide dismutase. Endothelial monolayer permeability was then measured by EC electrical resistance or by the leakage of horseradish peroxide (HRP) passing through filters. Endothelial junctional protein distribution and expression of VE-cadherin and occludin were determined by fluorescent staining of endothelial monolayer and by Western blot analysis. mRNA expressions for VE-cadherin and occludin were determined by reverse transcriptase-polymerase chain reaction. Data are expressed as Omega. cm(2) for electrical resistance and DeltaOD 470 nm for HRP assay and presented as mean +/- standard error of the mean. Analysis of variance was used for statistical analysis. A P value less than.05 was considered statistically significant. Endothelial cell electrical resistance was decreased and HRP leakage was increased in ECs treated with PAF. Intercellular gaps were formed at cell contact regions in ECs treated with PAF, as evaluated by staining of junctional protein VE-cadherin and occludin. The functional changes of the EC barrier and the formation of intercellular gaps induced by PAF were concentration dependent, which could be partially attenuated by pretreatment of ECs with SOD. Total cellular junctional protein expression and mRNA expression of VE-cadherin and occludin were not affected by PAF. Increased EC monolayer permeability induced by platelet-activating factor is associated with disorganization of EC junctional protein distribution of VE-cadherin and occludin. Superoxide dismutase partially attenuated the PAF-induced increased endothelial monolayer permeability, which suggests that oxidative stress might be involved in the process of PAF-induced disturbances of endothelial barrier function.
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PMID:Antioxidant superoxide dismutase attenuates increased endothelial permeability induced by platelet-activating factor. 1251 87

Lung cells import iron across the plasma membrane as ferrous (Fe2+) ion by incompletely understood mechanisms. We tested the hypothesis that human bronchial epithelial (HBE) cells import non-transferrin-bound iron (NTBI) using superoxide-dependent ferri-reductase activity involving anion exchange protein 2 (AE2) and extracellular bicarbonate (HCO3-). HBE cells that constitutively express AE2 mRNA by reverse transcriptase-polymerase chain reaction and AE2 protein by Western analysis avidly transported NTBI after exposure to either Fe2+ or Fe3+, but reduction of Fe3+ to Fe2+ was first required. The ability of HBE cells to reduce Fe3+ and transport Fe2+ was inhibited by active extracellular superoxide dismutase (SOD). Similarly, HBE cells that overexpress Cu,Zn SOD after adenoviral infection with AdSOD1 showed diminished iron uptake. The role of AE2 in iron uptake was indicated by three lines of evidence: (i) lack of both iron reduction and iron transport in bicarbonate-free buffer at controlled pH, (ii) failure of HBE cells treated with stilbene AE inhibitors to reduce Fe3+ or transport iron, and (iii) inhibition of iron uptake in HBE cells by inhibition of AE2 protein expression with antisense oligonucleotides. We thus disclose a novel ferri-reductase mechanism of NTBI uptake by human lung cells that employs superoxide exchange for HCO3- by AE2 protein in the plasma membrane.
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PMID:Superoxide-dependent iron uptake: a new role for anion exchange protein 2. 1279 78

The aim of this work was to study the induction and secretion of interleukin 8 (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and secretion were determined in the presence of the toxics, and the effect of antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide dismutase and glutathione peroxidase activities were determined. Lipid peroxidation increased significantly only in Ac-treated cells. All toxics failed to decrease significantly the intracellular levels of reduced GSH. Catalase activity was diminished in all treatments, while other enzyme activities did not present changes. No change in peroxide production was found with any treatment. IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)-treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase chain reaction results correlated with secretion values. Our results show that Ac and LPS treatment produced an increased IL-8 induction and secretion. Oxidative stress and TNF-alpha are mediators in IL-8 response. This observation suggests that in the in vivo liver, the mechanism of ethanol-induced IL-8 production requires ethanol metabolism, and hepatocytes do not require the interaction among different populations of liver cells to respond.
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PMID:Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide. 1280 41

Our previous study demonstrated that polycationic liposomes are highly stable in the bloodstream and represent an effective agent for liver gene delivery. We report here that liposome-mediated extracellular superoxide dismutase (EC-SOD) gene delivery successfully prevented acute liver injury in mice. The therapeutic efficacy of EC-SOD gene delivery by polycationic liposomes was determined against the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in a mouse model of acute liver injury caused by D-galactosamine and lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD plasmid led to a striking increase in superoxide dismutase activity in the medium. The transfected cells had much less cell death after reactive oxygen species exposure compared with untransfected or control plasmid-transfected cells. In a model of acute liver injury, serum alanine aminotransferase levels in mice receiving portal vein injections of EC-SOD lipoplexes were much lower than in those receiving normal saline, liposomes alone, or control lipoplexes. Liver histology confirmed that there was less cell death in the EC-SOD lipoplex-treated group. Quantitative reverse transcriptase polymerase chain reaction showed a 55-fold increase in human EC-SOD gene expression in the liver of mice injected with EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated mice was higher than in the control groups; this was associated with higher liver glutathione levels and reduced lipid peroxidation. In conclusion, polycationic liposome-mediated EC-SOD gene delivery protects against reactive oxygen species toxicity in vitro and against lipopolysaccharide-induced acute liver injury in D-galactosamine-sensitized mice.
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PMID:Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice. 1523 3

Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cell neurons (CGCs) against apoptosis induced by K+ and serum deprivation. However, the precise mechanism of this protection remains unknown. We recently reported that the transcription factor nuclear factor kappa B (NF-kappaB) is activated in PEDF-treated CGCs. Although it is well known that NF-kappaB blocks apoptotic cell death through the induction of pro-survival factors, the effects of PEDF on the expression of these factors are not fully understood. In this study, we employed the use of reverse transcriptase-polymerase chain reaction to analyze the gene expression of certain pro-survival genes and found that genes such as c-IAP1, c-IAP2, FLIPs, A1/Bfl-1 and Mn-SOD were induced in PEDF-treated neurons. On the other hand, no induction was observed of the pro-apoptotic Bcl-2 family members Bax and Bid at any time from 3 to 24 h following PEDF addition. Furthermore, phosphorylation of cyclic AMP-responsive element binding protein (CREB) and increment of nuclear cyclic AMP-response element (CRE)-like DNA binding were observed in PEDF-treated CGCs. The anti-apoptotic effect of PEDF was blocked by overexpression of dominant negative CREB or a mutated form of IkappaBalpha. These results suggested that induction of both CRE- and NF-kappaB-dependent genes is required for the observed neuroprotective effects of PEDF on CGCs.
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PMID:Pigment epithelium-derived factor induces pro-survival genes through cyclic AMP-responsive element binding protein and nuclear factor kappa B activation in rat cultured cerebellar granule cells: Implication for its neuroprotective effect. 1589 82

Our previous study reported that oxysterol cholestane-3beta,5 alpha, 6 beta-triol (Triol) induced vascular smooth muscle cells (VSMCs) apoptosis, which was inhibited by selenium pretreatment. To further investigate the mechanisms of the inhibition, the glutathione peroxidase (GPx) activity, the total antioxidant capacity (T-AOC), the total superoxide dismutase (SOD) activity, and the level of lipid peroxidation (the content of malondialdehyde, MDA) of VSMCs were measured, and fluidity of cell membrane, reactive oxygen species (ROS) level, the reduction of mitochondrial membrane potential (Delta psi(m)), and the intracellular Ca(2+) in single cell were detected using several fluorescence indicators. Meanwhile, the mRNA levels of c-myc, bcl-2, GPx, and thioredoxin reductase (TR) were measured by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results showed that the decrease of GPx activity, T-AOC, SOD activity, the fluidity of cell membrane, the Delta psi(m), and the mRNA expression of c-myc, bcl-2, GPx, and TR of VSMCs and the increase of MDA, ROS generation, and intracellular Ca(2+), significantly induced by Triol (10 microM, 24h) were inhibited to a different extent, respectively, when cells were pretreated with sodium selenite (50 nM, 12 or 24h) before exposure to Triol. These effects were time dependent and enhanced with prolongation of the time of pretreatment. In conclusion, the results in the present work showed that the mechanism of selenium inhibition of cell apoptosis induced by oxysterols in rat VSMCs was related with the antioxidation of selenoproteins.
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PMID:Mechanisms of selenium inhibition of cell apoptosis induced by oxysterols in rat vascular smooth muscle cells. 1603 82

Erythropoietin (Epo) expression, which regulates erythropoiesis, has been shown in rat and mouse brain after hypoxia. A previous study from our laboratory showed that astrocytes from manganese-superoxide dismutase (SOD2) homozygous knockout (SOD2(-/-)) mice can survive under 5% O(2), but not under normal aerobic conditions. However, the mechanism involved is not clear. Our preliminary study using reverse transcriptase-polymerase chain reaction showed increased Epo mRNA expression in astrocytes cultured with 5% hypoxia compared with astrocytes under normal conditions. After administration of anti-sense Epo, protection decreased with time. Dose-dependent administration of Epo to SOD2(-/-) mouse astrocytes improved their survivability under normal conditions. Survivability of heterozygous SOD2(-/+) mutant and wild-type mouse astrocyte cultures was the same under normal conditions but, after administration of 2 mM of paraquat, a reactive oxygen species generator, survivability of the SOD2(-/+) astrocytes decreased remarkably compared with the wild-type cells. Epo administration 24 h before exposure to paraquat significantly improved the survivability of the SOD2(-/+) astrocytes. Western blot studies suggest that Jak-Stat signal transduction pathways are involved in this process. Our study demonstrates an important role for Epo in the protection of astrocytes from reactive oxygen species. We suggest that Epo can compensate in part for the antioxidant properties of mitochondrial SOD2 deficiency.
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PMID:Epo protects SOD2-deficient mouse astrocytes from damage by oxidative stress. 1628 65


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