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)

Reactive oxygen species (ROS) are known mediators of intracellular signaling cascades. Excessive production of ROS may, however, lead to oxidative stress, loss of cell function, and ultimately apoptosis or necrosis. A balance between oxidant and antioxidant intracellular systems is hence vital for cell function, regulation, and adaptation to diverse growth conditions. Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous oxidoreductase system with antioxidant and redox regulatory roles. In mammals, extracellular forms of Trx also have cytokine-like effects. Mammalian TrxR has a highly reactive active site selenocysteine residue resulting in a profound reductive capacity, reducing several substrates in addition to Trx. Due to the reactivity of TrxR, the enzyme is inhibited by many clinically used electrophilic compounds including nitrosoureas, aurothioglucose, platinum compounds, and retinoic acid derivatives. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In this review, we focus on the reactions of the Trx system with ROS molecules and different cellular antioxidant enzymes. We summarize the TrxR-catalyzed regeneration of several antioxidant compounds, including ascorbic acid (vitamin C), selenium-containing substances, lipoic acid, and ubiquinone (Q10). We also discuss the general cellular effects of TrxR inhibition. Dinitrohalobenzenes constitute a unique class of immunostimulatory TrxR inhibitors and we consider the immunomodulatory effects of dinitrohalobenzene compounds in view of their reactions with the Trx system.
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PMID:Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. 1172 1

Exercise increases oxygen consumption and causes a disturbance of intracellular pro-oxidant-antioxidant homeostasis. Few data are available as to the cumulative effects of exercise on the antioxidant defenses of the neutrophil. We studied the effects of 90 days' supplementation with placebo or an antioxidant cocktail of vitamin E (500 mg/day) and beta-carotene (30 mg/day) and the last 15 days also with vitamin C (1 g/day) on sportsmen's basal neutrophil antioxidant defenses. We analyzed the activities of catalase, glutathione peroxidase, glutathione reductase and the activities and levels of superoxide dismutase, glutathione and glutathione disulfide in neutrophils purified from antecubital vein blood of sportsmen before and after diet supplementation. Plasma vitamin E, beta-carotene and vitamin C concentrations in the antioxidant-supplemented group were approximately 1.6, 10, and 1.2 times higher respectively than those of the placebo group. The antioxidant-supplemented group presented a significantly higher glutathione versus glutathione disulfide ratio in neutrophils (about 20%) than the placebo one. Antioxidant supplementation enhances the antioxidant enzyme activity of superoxide dismutase and catalase in neutrophils.
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PMID:Diet supplementation with vitamin E, vitamin C and beta-carotene cocktail enhances basal neutrophil antioxidant enzymes in athletes. 1188 77

Melatonin was found to be a potent free radical scavenger in 1993. Since then over 800 publications have directly or indirectly confirmed this observation. Melatonin scavenges a variety of reactive oxygen and nitrogen species including hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide and peroxynitrite anion. Based on the analyses of structure-activity relationships, the indole moiety of the melatonin molecule is the reactive center of interaction with oxidants due to its high resonance stability and very low activation energy barrier towards the free radical reactions. However, the methoxy and amide side chains also contribute significantly to melatonin's antioxidant capacity. The N-C=O structure in the C3 amide side chain is the functional group. The carbonyl group in the structure of N-C=O is key for melatonin to scavenge the second reactive species and the nitrogen in the N-C=O structure is necessary for melatonin to form the new five membered ring after melatonin's interaction with a reactive species. The methoxy group in C5 appears to keep melatonin from exhibiting prooxidative activity. If the methoxy group is replaced by a hydroxyl group, under some in vitro conditions, the antioxidant capacity of this molecule may be enhanced. However, the cost of this change are decreased lipophility and increased prooxidative potential. Therefore, in in vivo studies the antioxidant efficacy of melatonin appears to be superior to its hydroxylated counterpart. The mechanisms of melatonin's interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through an radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4 and C7 and nitrosation. Melatonin also has the ability to repair damaged biomolecules as shown by the fact that it converts the guanosine radical to guanosine by electron transfer. Unlike the classical antioxidants, melatonin is devoid of prooxidative activity and all known intermediates generated by the interaction of melatonin with reactive species are also free radical scavengers. This phenomenon is defined as the free radical scavenging cascade reaction of the melatonin family. Due to this cascade, one melatonin molecule has the potential to scavenge up to 4 or more reactive species. This makes melatonin very effective as an antioxidant. Under in vivo conditions, melatonin is often several times more potent than vitamin C and E in protecting tissues from oxidative injury when compared at an equivalent dosage (micromol/kg). Future research in the field of melatonin as a free radical scavenger might be focused on: 1), signal transduction and antioxidant enzyme gene expression induced by melatonin and its metabolites, 2), melatonin levels in tissues and in cells, 3), melatonin structure modifications, 4), melatonin and its metabolites in plants and, 5), clinical trials using melatonin to treat free radical related diseases such as Alzheimer's, Parkinson's, stroke and heart disease.
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PMID:Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. 1189

The contribution of oxidative stress, different types of DNA damage and expression of DNA repair enzymes in colon and liver mutagenesis induced by 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) was investigated in four groups of six Big Blue rats fed diets with 0, 20, 70, and 200 mg IQ/kg for 3 weeks. There were dose-response relationships of DNA adducts ((32)P-postlabeling) and DNA strand breaks (comet assay) in colon and liver tissues, with the highest levels of DNA adducts and strand breaks in the colon. There was dose-dependent induction of mutations in both the colon and the liver, and the same IQ dose produced two-fold more cII mutations in the liver compared with the colon. The IQ-induced mutation spectrum in the colon was not significantly different to that of control rats. The expression of ERCC1 and OGG1 was higher in the colon than liver, and was unaffected by the IQ diet. Investigations of oxidative stress biomarkers produced inconclusive results. Oxidative DNA damage detected by the endonuclease III enzyme and 7-hydro-8-oxo-2'-deoxyguanosine in colon, liver and/or urine was unaltered by IQ. However, there was increased level of gamma-glutamyl semialdehyde in liver proteins, indicating a higher rate of protein oxidation in the liver following IQ administration. In plasma and erythrocytes there were unaltered levels of oxidized protein, malondialdehyde, and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase) indicating no systemic oxidative stress. However, the level of total vitamin C was increased in plasma, with the largest fraction being in the reduced form. In conclusion, our results indicate that DNA adducts rather than oxidative stress are responsible for the initiation of IQ-induced carcinogenesis of the liver and colon. A lower frequency of mutations in the colon than in the liver could be related to higher expression of DNA repair enzymes in the former.
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PMID:Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in colon and liver of Big Blue rats: role of DNA adducts, strand breaks, DNA repair and oxidative stress. 1215 58

1-Cys peroxiredoxin (1-cysPrx) is a novel antioxidant enzyme able to reduce phospholipid hydroperoxides in vitro by using glutathione as a reductant. This enzyme is widely expressed and is enriched in lungs. A fusion protein of green fluorescent protein with 1-cysPrx was stably expressed in a lung-derived cell line (NCI-H441) lacking endogenous enzyme. Overexpressing cells (C17 or C48) degraded H(2)O(2) and t-butylhydroperoxide more rapidly and showed decreased sensitivity to oxidant stress as measured by (51)Cr release. On exposure to (*)OH generated by Cu(2+)-ascorbate (Asc), overexpressing cells compared with H441 showed less increase in thiobarbituric acid-reactive substance and phosphatidylcholine hydroperoxide content. This effect was reversed by depletion of cellular glutathione. Diphenyl-1-pyrenoylphosphonium fluorescence, used as a real-time probe of membrane phospholipid peroxidation, increased immediately on exposure to Cu(2+)-Asc and was abolished by preincubation of cells with Trolox (a soluble vitamin E) or Tempol (a radical scavenger). The rate of diphenyl-1-pyrenoylphosphonium fluorescence increase with Cu(2+)-Asc exposure was markedly attenuated in C17 and C48 cells as compared with H441. Annexin V-Cy3 was used to detect phosphatidylserine translocation from the inner to outer leaflet of the plasma membrane. Cu(2+)-Asc treatment induced phosphatidylserine translocation within 2 h in H441 cells but none was observed in C48 cells up to 24 h. These results indicate that 1-cysPrx can scavenge peroxides but in addition can reduce peroxidized membrane phospholipids. Thus, the enzyme can protect cells against oxidant-induced plasma membrane damage, thereby playing an important role in cellular defense against oxidant stress.
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PMID:1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage. 1219 53

Photosynthetic and antioxidant responses following exposure to either ultraviolet-A or ultraviolet-B were contrasted in two species of the unicellular green alga, DUNALIELLA: Species selection was based on the ability of Dunaliella bardawil (UTEX 2538) to accumulate inter-thylakoid beta-carotene when subjected to environmental stress while Dunaliella salina (UTEX 200) lacks this ability. Cells were cultured in high and low levels of visible light (150 and 35 micro mol photons m(-2 )s(-1), respectively) and then either ultraviolet-A (320-400 nm) or ultraviolet-B (290-320 nm) was added to visible light for 24-h exposure. A potassium chromate solution was found to be an ideal screen for removal of ultraviolet-A and ultraviolet-C from ultraviolet-B radiation. There were no significant changes in photosynthetic or antioxidant parameters following exposure to ultraviolet-B. Ultraviolet-A exposure significantly decreased photosynthetic parameters (>70% decrease in Fv/Fm and the ratio of light-limited to light-saturated photosynthesis in low beta-carotene cells) and resulted in 50% increases in ascorbate peroxidase activity and ascorbate concentrations. The results suggest exposure to ultraviolet-A (but not ultraviolet-B) directly affects photosynthesis, observed as a loss of photosystem II electron transport efficiency and increased radical formation. This research indicates that the accumulated beta-carotene in D. bardawil prevents UV-related photosynthetic damage through blue-light/ultraviolet-A absorption (supported by trends observed for antioxidant enzyme responses).
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PMID:Contrasting effects of UV-A and UV-B on photosynthesis and photoprotection of beta-carotene in two Dunaliella spp. 1219 90

Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women. The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects. Pycnogenol is a standardized extract of the bark of the French maritime pine (Pinus pinaster), a well-known, potent antioxidant. Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition, it recycles vitamin C, regenerates vitamin E and increases the endogenous antioxidant enzyme system. Pycnogenol protects against ultraviolet (UV) radiation. Therefore its efficacy in the treatment of melasma was investigated. Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily, i.e. 75 mg Pycnogenol per day. These patients were evaluated clinically by parameters such as the melasma area index, pigmentary intensity index and by routine blood and urine tests. After a 30-day treatment, the average melasma area of the patients decreased by 25.86 +/- 20.39 mm(2) (p < 0.001) and the average pigmentary intensity decreased by 0.47 +/- 0.51 unit (p < 0.001). The general effective rate was 80%. No side effect was observed. The results of the blood and urine test parameters at baseline and at day 30 were within the normal range. Moreover, several other associated symptoms such as fatigue, constipation, pains in the body and anxiety were also improved. To conclude, Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma.
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PMID:Treatment of melasma with Pycnogenol. 1223 16

We demonstrated that exposure of cells to 50 nM okadaic acid for 2 h induced a reduction in cellular glutathione transferase, glutathione reductase and catalase activity. Likewise, this acid prompted an increase in lipid peroxidation. Treatment of cells with 10(-5) M melatonin or 0.5 microg/ml vitamin C prevented the effects of okadaic acid. These results indicate that okadaic acid induces an oxidative stress imbalance, while melatonin and vitamin C prevent the oxidative stress induced by okadaic acid. Likewise, these data indicate the great importance of oxidative stress in both this experimental model and in the development and course of neurodegenerative disease, especially Alzheimer's disease. They show that melatonin is much more efficient than vitamin C in reducing the extent of oxidative stress. This phenomenon was demonstrated by the smaller dose of melatonin needed to obtain effects similar to those obtained with vitamin C on lipid peroxidation and by the protective effect of melatonin on antioxidant enzyme activity.
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PMID:Comparison of melatonin versus vitamin C on oxidative stress and antioxidant enzyme activity in Alzheimer's disease induced by okadaic acid in neuroblastoma cells. 1224 84

Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zinc's antioxidant role in protecting against free radical-induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health. Abundant evidence demonstrates the antioxidant role of zinc. Topical zinc, in the form of divalent zinc ions, has been reported to provide antioxidant photoprotection for skin. Two antioxidant mechanisms have been proposed for zinc: zinc ions may replace redox active molecules, such as iron and copper, at critical sites in cell membranes and proteins; alternatively, zinc ions may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. No matter how they work, topical zinc ions may provide an important and helpful antioxidant defense for skin.
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PMID:Evidence supporting zinc as an important antioxidant for skin. 1235 35

The cellular antioxidant system appears to protect cochlear hair cells from oxidative stress due to noise and aging. The role of individual metabolic variables remains poorly understood, however. We examined the role of a number of metabolic factors on human cochlear function in noise-exposed individuals. In 58 factory workers we measured audiometry and distortion product otoacoustic emissions prior to a workshift. Simultaneously we measured levels of vitamin E, vitamin C, and polymorphism status for two metabolic genes related to glutathione S-transferase function (GSTM1 and GSTT1). Age and total noise exposure were predictive of hearing status. Vitamin E levels were negatively correlated with hearing function, and this effect was partly explained by an increase in vitamin E levels with age. No effect was found for vitamin C. Individuals possessing the GSTM1 gene had significantly better high frequency otoacoustic emissions compared to GSTM1 null individuals. The protective effect of GSTM1 was present even after adjusting for age, race, sex, and years of noise exposure. GSTT1 did not exhibit a similarly protective effect. While the cross-sectional nature of the study precludes drawing conclusions about causation, these data suggest that GSTM1, an antioxidant enzyme which is found in the mammalian cochlea, may play a protective role in humans against hair cell damage due to noise or aging.
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PMID:Antioxidant status and hearing function in noise-exposed workers. 1237 44


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