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)

The combined effect of creatine (Cr) or estrogen (E(2)) with exercise training on cardiac reserve function and antioxidant reservation against oxidative stress were investigated in ovariectomized female Golden Syrian hamsters. One hundred animals were divided into nonexercise and exercise-trained groups, in which each group was separated into the control and 4 treatments of Cr depletion (Cr-), Cr supplementation (Cr+), E(2) replacement (E(2)), and Cr supplementation combined with E(2) replacement (Cr+E (2)). In the exercise-trained group, wheel-running exercise (10 minutes a day, 5 days a week) was imposed for 9 weeks. After the animals were sacrificed, several indicators of cardiac function, specifically the corrected QT interval, left ventricular developed pressure (LVDP), and maximum rate of rise (dP/dt(max)) against a hydrogen peroxide (H(2)O(2)) stress test were measured in isolated hearts using the Langendorff apparatus. Markers of oxidative stress, in other words, reduced glutathione (GSH), oxidized glutathione (GSSG), and an antioxidant enzyme, glutathione peroxidase (GPx) were determined. Exercise-trained animals could restore cardiac reserve function and antioxidant levels against oxidative damage (P<0.05). Cr+, E(2) , and Cr+E(2) combined with exercise training showed highly protected cardiac reserve function against oxidative stress compared to Cr+, E(2) , and Cr+E(2) without exercise (P<0.05). The myocardial antioxidant levels were improved greatly in E(2) and Cr+E(2) combined with exercise training (P<0.05). In conclusion, estrogen replacement and creatine supplementation plus estrogen replacement when combined with exercise training show significant protective effects for cardiac reserve function and antioxidant reservation against oxidative stress in estrogen-deficient hamsters.
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PMID:Protective effect of creatine supplementation and estrogen replacement on cardiac reserve function and antioxidant reservation against oxidative stress in exercise-trained ovariectomized hamsters. 1861 91

As an initial subdeficient status of zinc, considered as an essential antioxidant trace element, is frequent in burned patients, we aim to assess the effects of low zinc dietary intakes on burn-induced oxidative stress, in an animal model. After 8 weeks of conditioning diets containing 80 ppm (control group) or 10 ppm of zinc (depleted group), Wistar rats were 20% TBSA burned and sampled 1-10 days after injury. Kinetic evolutions of zinc status, plasma oxidative stress parameters, and antioxidant enzymes were also studied in blood and organs. The zinc-depleted diet induced, before injury, a significant decrease in zinc bone level and the increase of oxidative stress markers without stimulation of antioxidant enzyme activity. After burn, more markedly in zinc depleted animals than in controls, zinc levels decreased in plasma and bone, while increasing in liver. The decrease of thiol groups and GSH/GSSG ratio and the depression of GPx activity in liver are also moderately emphasized. Nevertheless, depleted zinc status could not be considered as determining for oxidative damages after burn injury. Further investigations must also be done to enlighten the mechanism of beneficial effects of zinc supplementation reported in burned patients.
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PMID:Burn-induced oxidative stress is altered by a low zinc status: kinetic study in burned rats fed a low zinc diet. 1877 51

Flavonoids are considered therapeutic agents in neurodegenerative disease because of their neuroprotective activity. This study investigated the neuroprotective effects of hesperetin in the brains of mice administered hesperetin at 10 or 50 mg/kg body weight (BW) for five weeks. Hesperetin inhibited biomarkers of oxidative stress, such as the level of thiobarbituric acid-reactive substance (TBARS) and carbonyl content, although there was a significant reduction at the higher dose of hesperetin. Moreover, at the higher dose, hesperetin significantly activated the catalase and total superoxide dismutase (SOD) activities. The same patterns were observed in the protein expression, and the expression of CuZn-SOD was more pronounced than that of Mn-SOD. The reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio was increased significantly in a dose-dependent manner, as well as the glutathione peroxidase (GSH-px) and glutathione reductase (GR) activities. Moreover, hesperetin did not induce apoptosis, even at the higher dose, as evidenced by caspase-3 expression and its activity. Based on these results, hesperetin may have a neuroprotective effect via the inhibition of oxidative damage, together with activation of the antioxidant enzyme system.
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PMID:Neuroprotective effects of chronic hesperetin administration in mice. 1902 42

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the ataxin-3 protein that confers a toxic gain of function. Because of the late onset of the disease, we hypothesize that the accumulated oxidative stress or/and defective antioxidant enzyme ability may be contributory factors in the pathogenesis of MJD. In this study, we utilized SK-N-SH and COS7 cells stably transfected with full-length MJD with 78 polyglutamine repeats to examine any alterations in the antioxidant activity. We demonstrated a significant reduction in the ratio of GSH/GSSG and total glutathione content (GSH + 2x GSSG) in mutant MJD cells compared with the wild-type cells under normal or stressful conditions. We also showed that both SK-N-SH-MJD78 and COS7-MJD78-GFP cell lines have lower activities of catalase, glutathione reductase, and superoxide dismutase compared with the wild-type cell lines. In addition, it is known that, when cells are under oxidative stress, the mitochondrial DNA is prone to damage. Our results demonstrated that mitochondrial DNA copy numbers are decreased in mutant cells and SCA3 patients' samples compared with the normal controls. Furthermore, the amount of common mitochondrial DNA 4,977-bp deletion is higher in SCA3 patients compared with that in normal individuals. Overall, mutant ataxin-3 may influence the activity of enzymatic components to remove O(2)(-) and H(2)O(2) efficiently and promote mitochondrial DNA damage or depletion, which leads to dysfunction of mitochondria. Therefore, we suggest that the cell damage caused by greater oxidative stress in SCA3 mutant cells plays an important role, at least in part, in the disease progression.
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PMID:Decreased antioxidant enzyme activity and increased mitochondrial DNA damage in cellular models of Machado-Joseph disease. 1918 26

Oxidative stress plays an important role in obesity-related metabolic diseases. Glutathione peroxidase (GPX) is an antioxidant enzyme downregulated in adipose tissue of obese mice. However, the role of GPX in adipocytes remains elusive. The objective of this study was to clarify the pathophysiological changes in GPX activity and glutathione metabolism and their roles in the pathogenesis of insulin resistance in adipocytes. To achieve this goal, we measured cellular GPX activity, glutathione (GSH) contents, GSH/GSSG ratio, and mRNA expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for de novo GSH synthesis, in adipose tissue of control and ob/ob mice and in 3T3-L1 adipocytes treated with insulin, H(2)O(2), free fatty acid (FFA), or TNFalpha. Furthermore, we investigated the effects of GPX inhibition with a specific GPX inhibitor or RNA interference against GPX, H(2)O(2), and reduced GSH on insulin signaling in 3T3-L1 adipocytes. ob/ob Mice showed not only a decrease in cellular activity of GPXs (GPX1, -4, and -7) but also an increase in gamma-GCS expression, resulting in increased GSH contents in adipose tissue. These alterations in glutathione metabolism were also observed during differentiation of 3T3-L1 cells and their exposure to insulin, FFA, or H(2)O(2). Inhibition of GPX activity, addition of GSH, and H(2)O(2) resulted in impaired insulin signaling in 3T3-L1 adipocytes. These results suggest that decreased GPX activity and increased gamma-GCS expression lead to overaccumulation of GSH, which might be involved in the pathogenesis of insulin resistance in obesity.
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PMID:Dysregulated glutathione metabolism links to impaired insulin action in adipocytes. 1936 77

Removal of reproductive 'sink' i.e. spikelets from wheat at anthesis delays the rate of flag leaf senescence. In this work, the antioxidant defense was studied in the flag leaf of Triticum aestivum cv. Kalyansona plants showing normal (S + plants) and delayed senescence via removal of spikelets (S- plants). This was done by measurement of metabolites and activities of enzymes such as superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase and glutathione reductase. S- plants had higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and antioxidant enzyme activities than the control plants and the differences were apparent from 21 days after anthesis (DAA). The removal of the reproductive sink led to an increased antioxidant defense which may be contributing towards the delayed flag leaf senescence in wheat. Chloroplasts and mitochondria, important sources of ROS, were isolated at two stages representing early (7 DAA) and late (21 DAA) senescence. Oxidative damage to proteins was studied in these organelles in relation to SOD and APX. Mitochondria had higher levels of damaged proteins than chloroplasts at 7 DAA in both S+ and S- plants. Higher damage was related to the lower antioxidant enzyme levels of SOD and APX in mitochondria as compared to chloroplasts.
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PMID:Delayed wheat flag leaf senescence due to removal of spikelets is associated with increased activities of leaf antioxidant enzymes, reduced glutathione/oxidized glutathione ratio and oxidative damage to mitochondrial proteins. 1939 42

Previous studies showed that salicylic acid (SA)-deficient transgenic Arabidopsis expressing the salicylate hydroxylase gene NahG had a higher tolerance to moderate salt stress. SA may potentiate the stress response of germination and growth of Arabidopsis seedlings by inducing reactive oxygen species (ROS). However, the detailed mechanism for a better adaption of NahG plants to moderate salt stress is largely unknown. In the present study we found that a higher GSH/GSSG (glutathione/oxidized glutathione) ratio and ASA/DHA (ascorbic acid/dehydroascorbate) ratio in NahG plants during the stress may be the key reason for their stress-tolerance advantage. NahG plants actually could not produce more active antioxidant enzymes than the wild-type ones under natural conditions, but maintain higher activities of glutathione reductase (GR) and dehydroascorbate reductase (DHAR) during the stress. Hereby, the reduced glutathione and reduced ascorbic acid contents are higher in NahG plants under salt stress. However, NahG plants do not adapt better under severe salt stress. All antioxidant enzyme activities, GSH/GSSG ratio and ASA/DHA ratio declined substantively at 400 mM NaCl stress in both NahG and wild-type seedlings.
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PMID:Lack of salicylic acid in Arabidopsis protects plants against moderate salt stress. 1952 18

Antenatal steroids have improved the survival of preterm infants; however, the mechanism of action is not fully understood. We aimed to establish an association between antenatal steroids and antioxidant activity and postnatal oxidative stress. In a prospective cohort study, extremely preterm neonates receiving antenatal steroids (CORT) or not (NOCORT) were enrolled. An association between antenatal steroids and activities of antioxidant enzymes and glutathione cycle enzymes in cord blood was found. In addition, reduced oxidative stress (GSH/GSSG ratio, CORT vs. NOCORT, 35.68 + or - 12.20 vs. 28.38 + or - 9.92; p < 0.01) and, decreased oxidation of proteins (ortho-tyrosine/phenylalanine ratio, CORT vs. NOCORT, 8.66 + or - 2.45 vs. 12.55 + or - 4.41; p < 0.01) and DNA (8oxodG/2dG ratio, CORT vs. NOCORT, 6.73 + or - 2.18 vs. 9.53 + or - 3.83; p < 0.01) also was found. Antenatal steroids were associated with reduced oxygen supplementation, mechanical ventilation, and conditions such as bronchopulmonary dysplasia, intra-periventricular hemorrhage, or retinopathy of prematurity. The maximal effectiveness was when steroids were administered 2-4 days before delivery. Female preterm infants had less oxidative stress and increased antioxidant activity and better clinical outcomes than did male infants, independent of receiving or not antenatal steroids. Antenatal steroids are accompanied by a reduction in postnatal oxidative-stress-derived conditions and increased antioxidant enzyme activity. Both these effects seem to be influenced by specific timing and female gender.
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PMID:Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing. 1964 72

Acylfulvenes (AFs) are a class of antitumor agents with favorable cytotoxic selectivity profiles compared to their natural product precursor, illudin S. Like many alkylating agents, illudin S and AFs readily react with thiol-containing small molecules such as cysteine, glutathione and cysteine-containing peptides; reduced cellular glutathione levels can affect illudin S toxicity. Glutathione reductase (GR) is a critical cellular antioxidant enzyme that regulates the intracellular ratio of reduced-oxidized glutathione. In this study, we found that acylfulvene analogues are GR inhibitors, and evaluated aspects of the drug-enzyme interactions as compared with the structurally related natural product illudin S and the known irreversible GR inhibitor, carmustine. Acylfulvene analogues exhibited concentration-dependent GR inhibitory activity with micromolar IC(50)s; however, up to 2 mM illudin S did not inhibit GR activity. The absence of NADPH attenuates GR inhibition by AFs and the presence of glutathione disulfide (GSSG), the natural GR substrate, which binds to the enzyme active site, has a minimal effect in protecting GR from AFs. Furthermore, each compound can induce GR conformation changes independent of the presence of NADPH or GSSG. These results, together with gel-filtration analysis results and mass spectrometry data, indicate AF is a reversible inhibitor and HMAF an irreversible inhibitor that can form a bis-adduct with GR by reacting with active site cysteines. Finally in a cell-based assay, illudin S and HMAF were found to inhibit GR activity, but this inhibition was not associated with the reduction of GR levels in the cell. A model accounting for differences in mechanisms of GR inhibition by the series of compounds is discussed.
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PMID:Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues. 1966 67

Manganese superoxide dismutase (SOD2) is a nuclear encoded and mitochondria localized antioxidant enzyme that converts mitochondria derived superoxide to hydrogen peroxide. This study investigates the hypothesis that mitochondria derived reactive oxygen species (ROS) regulate ionizing radiation (IR) induced transformation in normal cells. Mouse embryonic fibroblasts (MEFs) with wild type SOD2 (+/+), heterozygous SOD2 (+/-), and homozygous SOD2 (-/-) genotypes were irradiated with equitoxic doses of IR, and assayed for transformation frequency, cellular redox environment, DNA damage, and cell cycle checkpoint activation. Transformation frequency increased ( approximately 5-fold) in SOD2 (-/-) compared to SOD2 (+/+) MEFs. Cellular redox environment (GSH, GSSG, DHE and DCFH-oxidation) did not show any significant change within 24 h post-IR. However, a significant increase in cellular ROS levels was observed at 72 h post-IR in SOD2 (-/-) compared to SOD2 (+/+) MEFs, which was consistent with an increase in GSSG in SOD2 (-/-) MEFs. Late ROS accumulation was associated with an increase in micronuclei frequency in SOD2 (-/-) MEFs. Exit from G(2) was accelerated in irradiated SOD2 (+/-) and SOD2 (-/-) compared to SOD2 (+/+) MEFs. These results support the hypothesis that SOD2 activity and mitochondria generated ROS regulate IR induced transformation in mouse embryonic fibroblasts.
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PMID:Mitochondrial ROS and radiation induced transformation in mouse embryonic fibroblasts. 1982 29


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