Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that mutations in mitochondrial DNA (mtDNA) can produce an increase in reactive oxygen species (ROS) and that this can play a major role in the pathogenic mechanisms of mitochondrial encephalomyopathies. Many studies exist using electron transport chain (ETC) inhibitors, however there are only a few studies that examine ROS production associated with mutations in the mtDNA. To investigate this issue, we have studied ROS production, antioxidant defences and oxidative damage to lipids and proteins in transmitochondrial cybrids carrying different mtDNA mutations. Here, we report that two different mutant cell lines carrying mutations in their mitochondrial tRNA genes (A3243G in tRNA LeuUUR and A8344G in tRNA Lys) showed an increased ROS production with a parallel increase in the antioxidant enzyme activities, which may protect cells from oxidative damage in our experimental conditions (no overt oxidative damage to lipids and proteins has been observed). In contrast, cytochrome c oxidase (COX) mutant cybrids (carrying the stop-codon mutation G6930A in the COXI gene) showed neither an increase in ROS production nor elevation of antioxidant enzyme activities or oxidative damage. These results suggest that the specific location of mutations in mtDNA has a strong influence on the phenotype of the antioxidant response. Therefore, this issue should be carefully considered when antioxidant therapies are investigated in patients with mitochondrial disorders.
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PMID:Enhanced ROS production and antioxidant defenses in cybrids harbouring mutations in mtDNA. 1616 71

Constant generation of Reactive oxygen species (ROS) during normal cellular metabolism of an organism is generally balanced by similar rate of consumption by antioxidants. Imbalance between ROS production and antioxidant defense results in increased level of ROS causing oxidative stress which leads to promotion of malignancy. Queuine is a hyper modified base analogue of guanine, found at first anti-codon position of Q- family of tRNAs. These tRNAs are completely modified with respect to queuosine in terminally differentiated somatic cells, however hypomodification of Q-tRNAs is close association with cell proliferation. Q-tRNA modification is essential for normal development, differentiation and cellular functions. Queuine is a nutrient factor to eukaryotes. It is found to promote cellular antioxidant defense system and inhibit tumorigenesis. The activities of antioxidant enzymes like catalase, SOD, glutathione peroxidase and glutathione reductase are found to be low in Dalton's lymphoma ascites transplanted (DLAT) mouse liver compared to normal. However, exogenous administration of queuine to DLAT mouse improves the activities of antioxidant enzymes. The results suggest that queuine promotes antioxidant defense system by increasing antioxidant enzyme activities and in turn inhibits oxidative stress and tumorigenesis.
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PMID:Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer. 1829 Jul 65

Oxidation-reduction (redox) reactions comprise a subset of fundamental biochemical reactions found throughout biological systems. While redox reactions are involved in many normal cellular functions, excess oxidative potential, or oxidative stress, can lead to cellular dysfunction and injury. Multiple protective antioxidant systems have evolved to guard against the adverse consequences of oxidant stress and injury. These systems include low-molecular-weight antioxidants, such as the glutathione-glutathione disulfide redox couple; the thiol proteome, whose various oxidation states can serve as a global redox buffer; and antioxidant enzymes, such as the superoxide dismutases, catalase, peroxidredoxins, and the glutathione peroxidases. One example of an essential antioxidant enzyme whose deficiency contributes to pathobiology in the vasculature is glutathione peroxidase-3 (GPx-3), the principal antioxidant enzyme in the extracellular compartment. This enzyme catalyzes the reduction of hydrogen and lipid peroxides to water and lipid alcohols, respectively, and does so using reducing equivalents provided by glutathione. As a selenoprotein, it requires unique translational machinery for its expression, as well as adequate selenium stores; its primary site of synthesis is the renal tubule, although all nucleated cells can express low levels of the enzyme. We have previously demonstrated that a deficiency of GPx-3 leads to enhanced platelet activation, and is an independent risk factor for acute ischemic stroke in the young. We recently developed a GPx-3-deficient mouse model, and demonstrated endothelial dysfunction as well as increased platelet-dependent thrombosis in an acute ischemic stroke model. Importantly, platelet inhibitors or small-molecule superoxide and hydrogen peroxide scavengers greatly attenuated the size of the ischemic stroke and its functional consequences in this model. These data support the importance of GPx-3as a key antioxidant enzyme that functions to limit arterial thrombosis in the setting of increased oxidant stress and endothelial dysfunction. A second example of an essential antioxidant enzyme whose deficiency contributes to pathobiology in the vasculature is glutathione peroxidase-1 (GPx-1), a central intracellular antioxidant. In our efforts to uncover a mechanism for the oxidative stress of hyperhomocysteinemia, we found that elevated levels of this amino acid is associated with a decrease in the expression and activity of GPx-1 in endothelial cells. This change in expression was found to be post-translational, and we recently demonstrated that it is a consequence of hypomethylation of selenocysteine (Sec)-charged tRNA. This modification is essential for appropriate incorporation of Sec into the selenoprotein GPx-1's active site during translation. Changes in Sec-tRNA methylation are brought about by increased S-adenosylhomocysteine, which inhibits the methyltransferase required to methylate Sec-tRNA to the Um34 form. These data suggest a unique mechanism for impaired GPx-1 expression in hyperhomocysteinemic states that directly relates to impaired cellular methylation potential caused by increased S-adenosylhomocysteine accumulation.
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PMID:Redox Dysregulation in Vascular Pathobiology. 2646 4

DNMT2 is a DNA/tRNA cytosine methyltransferase that is highly conserved in structure and function in eukaryotes. In plants however, limited information is available on the function of this methyltransferase. We have previously reported that in the moss Physcomitrella patens, DNMT2 plays a crucial role in stress recovery and tRNAAsp transcription/stability under salt stress. To further investigate the role of PpDNMT2 at genome level, in this study we have performed RNA sequencing of ppdnmt2. Transcriptome analysis reveals a number of genes and pathways to function differentially and suggests a close link between PpDNMT2 function and osmotic and ionic stress tolerance. We propose PpDNMT2 to play a pivotal role in regulating salt tolerance by affecting molecular networks involved in stress perception and signal transduction that underlie maintenance of ion homeostasis in cells. We also examined interactome of PpDNMT2 using affinity purification (AP) coupled to mass spectrometry (AP-MS). Quantitative proteomic analysis reveals several chloroplast proteins involved in light reactions and carbon assimilation and proteins involved in stress response and some not implicated in stress to co-immunoprecipitate with PpDNMT2. Comparison between transcriptome and interactome datasets has revealed novel association between PpDNMT2 activity and the antioxidant enzyme Superoxide dismutase (SOD), protein turnover mediated by the Ubiquitin-proteasome system and epigenetic gene regulation. PpDNMT2 possibly exists in complex with CuZn-SODs in vivo and the two proteins also directly interact in the yeast nucleus as observed by yeast two-hybrid assay. Taken together, the work presented in this study sheds light on diverse roles of PpDNMT2 in maintaining molecular and physiological homeostasis in P. patens. This is a first report describing transcriptome and interactome of DNMT2 in any land plant.
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PMID:Transcriptome Analysis of ppdnmt2 and Identification of Superoxide Dismutase as a Novel Interactor of DNMT2 in the Moss Physcomitrella patens. 3284 34

The use of irrigation water containing arsenic (As) had led to large areas of As-contaminated farmland, and as a result, plants and food have become severely poisoned. Humic acid (HA) can be complexed with metals, which in turn affects the metals' behavior. Herein, we explored the accumulation of arsenate in lettuce treated with different concentrations of arsenate and studied the effects of HA on the accumulation and toxicity of arsenate. The addition of HA did not cause significant changes in the arsenate content in lettuce but had a significant effect on the activity of antioxidant enzymes, which improved the antioxidant capability of the lettuce plants. Furthermore, HA promoted the accumulation of nutrients, such as magnesium (Mg), calcium (Ca), molybdenum (Mo) and manganese (Mn), in the leaves. Arsenate disrupted metabolic pathways, such as amino acid metabolism, carbohydrate metabolism, and aminoacyl-tRNA biosynthesis. The addition of HA increased the contents of amino acids and sugars, thereby improving lettuce growth. The present study explored the effects of HA on As accumulation and related physiological changes (antioxidant enzyme activities, absorption of nutrients and metabolic mechanisms) and provided insights into the regulation of As contamination by HA, which is relatively inexpensive.
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PMID:Arsenate phytotoxicity regulation by humic acid and related metabolic mechanisms. 3301 91