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)

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

Catalase, Mn-superoxide dismutase (MnSOD) and Cu,Zn-superoxide dismutase (CuZnSOD) activities were studied in rat liver and kidney 6-48 h after CdCl(2) intraperitoneal administration or 10-30 days daily oral CdCl(2) intake in drinking water. This approach provided some indications as to the sensitivity of each enzyme to cadmium toxicity. These experiments showed that the formation of thiobarbituric acid reactive substance (TBARS) did not strictly depend on how well the antioxidant enzyme worked. From in vitro experiments it appeared that TBARS removal by vitamin E did not restore the three enzyme activities at all. As for cadmium's inhibitory mechanism on catalase activity, our data, obtained in the pH range 6.0-8.0, are a preliminary indication that the negative effect of this metal is probably due to imidazole residue binding of His-74 which is essential in the decomposition of hydrogen peroxide. Cadmium inhibition of liver mitochondrial MnSOD activity was completely removed by Mn(2+) ions, suggesting that the reducing effect on this enzyme is probably due to the substitution of cadmium for manganese. We also observed the antioxidant capacity of Mn(2+) ions, since they were able to normalize the increased TBARS levels occurring when liver mitochondria were exposed to cadmium. The reduced activity of CuZnSOD does not seem to be due to the replacement of Zn by Cd, nor to the peroxides formed. As this enzyme activity was almost completely recovered after 48 h, we hypothesize that the momentary inhibition is imputable to a cadmium/enzyme interaction. This causes some perturbation in the enzyme topography which is critical for its catalytic activity. The pathological implications linked to antioxidant enzyme disorders induced by cadmium toxicity are discussed.
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PMID:Molecular inhibitory mechanisms of antioxidant enzymes in rat liver and kidney by cadmium. 1220 41

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

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

1-cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin superfamily, reduces phospholipid hydroperoxides as well as organic peroxides and H(2)O(2). To determine the physiological function(s) of 1-cysPrx, we have used an antisense strategy to suppress endogenous 1-cysPrx in L2 cells, a rat lung epithelial cell line. A 25-base antisense morpholino oligonucleotide was designed to bind a complementary sequence overlapping the translational start site (-18 to +7) in the rat 1-cysPrx mRNA, blocking protein synthesis. Treatment with an antisense oligonucleotide for 48 h resulted in approximately 60% suppression of the 1-cysPrx protein content as measured by immunoblot analysis and an approximately 44% decrease of glutathione peroxidase activity as compared with random oligonucleotide treated and control (vehicle only) cells. Accumulation of phosphatidylcholine hydroperoxide in plasma membranes was demonstrated by high pressure liquid chromatography assay for conjugated dienes (260 pmol/10(6) cells for antisense versus 70 pmol/10(6) cells for random oligonucleotide and control cells) and by fluorescence of diphenyl-1-pyrenylphosphine, a probe for lipid peroxidation. The percentage of cells showing positive staining for annexin V and propidium iodide after antisense treatment was 40% at 28 h and 80% at 48 h. TdT-mediated dUTP nick end labeling assay at 48 h indicated DNA fragmentation in antisense-treated cells that was blocked by prior infection with adenovirus encoding 1-cysPrx or by pretreatment with a vitamin E analogue. The results indicate that 1-cysPrx can function in the intact cell as an antioxidant enzyme to reduce the accumulation of phospholipid hydroperoxides and prevent apoptotic cell death.
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PMID:An antisense oligonucleotide to 1-cys peroxiredoxin causes lipid peroxidation and apoptosis in lung epithelial cells. 1237 39

Determination of reliable bioindicators of diabetes-induced oxidative stress and the role of dietary vitamin E supplementation were investigated. Blood (plasma) chemistries, lipid peroxidation (LPO), and antioxidant enzyme activities were measured over 12 weeks in New Zealand White rabbits (control, diabetic, and diabetic + vitamin E). Cholesterol and triglyceride levels did not correlate with diabetic state. Plasma LPO was influenced by diabetes and positively correlated with glucose concentration only, not cholesterol or triglycerides. Liver glutathione peroxidase (GPX) activity negatively correlated with glucose and triglyceride levels. Plasma and erythrocyte GPX activities positively correlated with glucose, cholesterol, and triglyceride concentrations. Liver superoxide dismutase activity positively correlated with glucose and cholesterol concentration. Vitamin E reduced plasma LPO, but did not affect the diabetic state. Thus, plasma LPO was the most reliable indicator of diabetes-induced oxidative stress. Antioxidant enzyme activities and types of reactive oxygen species generated were tissue dependent. Diabetes-induced oxidative stress is diminished by vitamin E supplementation.
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PMID:Differential indicators of diabetes-induced oxidative stress in New Zealand White rabbits: role of dietary vitamin E supplementation. 1245 60

Lipid peroxidation has been implicated in a variety of pathophysiological processes, including inflammation, atherogenesis, neurodegeneration, and the ageing process. Phospholipid hydroperoxide glutathione peroxidase (GPX4) is the only major antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha tocopherol (vitamin E) to inhibit lipid peroxidation. Here we describe the generation and characterization of GPX4-deficient mice by targeted disruption of the murine Gpx4 locus through homologous recombination in embryonic stem cells. Gpx4(-/-) embryos die in utero by midgestation (E7.5) and are associated with a lack of normal structural compartmentalization. Gpx4(+/-) mice display reduced levels of Gpx4 mRNA and protein in various tissues. Interestingly, cell lines derived from Gpx4(+/-) mice are markedly sensitive to inducers of oxidative stress, including gamma-irradiation, paraquat, tert-butylhydroperoxide, and hydrogen peroxide, as compared to cell lines derived from wild-type control littermates. Gpx4(+/-) mice also display reduced survival in response to gamma-irradiation. Our observations establish GPX4 as an essential antioxidant enzyme in mice and suggest that it performs broad functions as a component of the mammalian antioxidant network.
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PMID:The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. 1256 75

Oxidative stress is implicated in the pathophysiology of a number of chronic diseases including atherosclerosis, diabetes, cataracts and accelerated aging. The aim of this study was to elucidate the protective role of vitamin E supplementation when oxidative stress is induced by CCl4 administration, using the rat as a model. Rats were fed diets for four weeks either with or without dl-alpha-tocopherol acetate supplementation. Half of the rats (n = 9) from each of the diet groups were then challenged with CCl4 at the completion of the four week diet period. Plasma levels of 8-iso-PGF(2alpha), antioxidant micronutrients and antioxidant enzyme activities were measured to examine changes in oxidative stress subsequent to the supplementation of dl-alpha-tocopherol in the diet. Plasma alpha-tocopherol (vitamin E) concentrations were higher for the groups supplemented with dl-alpha-tocopherol acetate, however the supplemented diet group that was subsequently challenged with CCl4 had significantly lower (p <0.001) plasma alpha-tocopherol concentration than the dl-alpha-tocopherol acetate diet group that was not challenged with CCl4. Total plasma 8-iso-PGF(2alpha) concentration was elevated in diet groups challenged with CCl4, however, the concentration was significantly lower (p <0.001) when the diet was supplemented with dl-alpha-tocopherol acetate. The antioxidant enzymes were not influenced by either dietary alpha-tocopherol manipulation or by the inducement of oxidative stress with CCl4. Plasma concentrations of trans-retinol (vitamin A) were reduced by CCl4 administration in both the dl-alpha-tocopherol acetate supplemented and unsupplemented diet groups. The results of this study indicate that dl-alpha-tocopherol acetate supplementation was protective of lipid peroxidation when oxidative stress is induced by a pro-oxidant challenge such as CCl4.
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PMID:Vitamin E supplementation in the mitigation of carbon tetrachloride induced oxidative stress in rats. 1277 Jun 45

Recent evidence suggests that impaired antioxidant status is involved in oxidative stress associated with diabetes. The main antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). The aim of the present investigation was to evaluate the activities and protein expression of these antioxidant enzymes in streptozotocin-induced diabetes. Furthermore, the effects of insulin and antioxidant therapy alone and in combination were studied. Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomly assigned to untreated, insulin-treated, antioxidant (vitamin E and C)-treated and insulin plus antioxidant-treated groups. Normal rats fed either a regular diet or the antioxidant (vitamin E and C)-rich diet served as controls. The animals were observed for 4 weeks. Diabetic animals showed marked weight loss, decreased activities of Cu Zn SOD and CAT and normal GPX activity. Additionally, the expression of all antioxidant enzyme proteins was decreased in the diabetic rats compared to the untreated controls. Insulin therapy prevented weight loss and normalized the activities and protein expression of all antioxidant enzymes. Antioxidant therapy in the diabetic rats normalized Cu Zn SOD and GPX protein expression. Combined therapy with insulin and antioxidants normalized all measured antioxidant enzyme protein expression and activities. Thus diabetes-associated reductions in antioxidant enzymes can be ameliorated by insulin and/or antioxidant therapy.
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PMID:Dysregulation of hepatic superoxide dismutase, catalase and glutathione peroxidase in diabetes: response to insulin and antioxidant therapies. 1500 Feb 96

Biological aging is associated with increased cellular levels of reactive oxygen species (ROS) as well as the formation and accumulation of oxidized biomolecules. During evolution, organisms developed a highly-efficient and adaptive antioxidant defense system. Antioxidants can generally be divided into two categories: enzymatic and non-enzymatic. During the aging process the activity of antioxidant enzymes, e.g. SOD, CAT, GSH-Px, and GSSG-R, depends on factors such as race, gender, tissue and subcellular localization of enzymes. The age-dependent decrease in antioxidant enzyme activity may be attributed to oxidative modifications of enzymes. During the aging process, ROS may also lead to the induction of some enzyme activity which is explained as an adaptive phenomenon. The decrease in GSH concentration with age can be explained by decreased GSH synthesis and/or increased GSH consumption in the removal of peroxides and xenobiotics. In plasma albumin, ferritin, transferrin, and caeruloplasmin exert protective action. Plasma proteins can inhibit ROS generation and lipid peroxidation by chelating free transition metals. Plasma protein concentrations changes with age. The major exogenous antioxidants, mostly derived from the diet, are vitamin E, C, A, and beta-carotene. During the aging process the level of vitamins may decrease or increase, depending on such factors as diet, and diseases.
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PMID:[Antioxidative abilities during aging]. 1507 54


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