Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is considered a pathogenic factor in many disorders. The capacity of dietary vitamin E to increase global antioxidant capacity and to decrease lipid peroxidation was studied in the guinea pig, an animal that cannot synthesize ascorbate. Male guinea pigs were subjected for 5 weeks to three diets differing in vitamin E content in the presence of optimum levels of vitamin C: group 15 (15 mg vitamin E/kg diet), group 150 (150 mg/kg), and group 1500 (1500 mg/kg). Hepatic vitamin E increased in the three groups in relation to the level of vitamin E in the diet. The increase in vitamin E between groups 15 and 150 was accompanied by a reduction in sensitivity to enzymatic lipid peroxidation. This did not occur between groups 150 and 1500. The different liver vitamin E concentrations did not affect the antioxidant enzymes superoxide dismutase, catalase, GSH-peroxidase and GSH-reductase, nor the non-enzymatic antioxidants vitamin C, GSH and ascorbate. It is concluded that dietary supplementation with vitamin E, at a level 6 times higher than the minimum daily requirement for guinea pigs, increases protection against hepatic lipid peroxidation without depressing endogenous antioxidant defences. Further increases in vitamin E to megadose levels did not provide additional protection from oxidative stress. The results also suggest that optimum levels of both vitamin C and vitamin E, simultaneously needed for protection against oxidative stress, are much higher than the minimum daily requirements.
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PMID:Vitamin E protects guinea pig liver from lipid peroxidation without depressing levels of antioxidants. 758 3

A metallothionein-I-transgenic mouse strain (MT-TG) was characterized to determine whether they would be suitable to study the functions of this protein. MT-TG mice were visually indistinguishable from nontransgenic littermate controls, but had 10- to 20-fold higher basal levels of MT protein in pancreas, liver, and stomach, as well as 2- to 6-fold higher MT protein levels in other organs (kidney, intestine, uterus, testes, spleen, heart, and lung) than control mice, as determined by the Cd/hemoglobin assay. The MT-TG mice had 50% more Zn in liver and 300% more Zn in pancreas than control mice. Interestingly, female MT-TG mice have 4- to 5-fold higher MT levels in liver than those of males. To determine whether MT can be further increased by well-known MT inducers, control and MT-TG mice were given Zn (200 mumol/kg), Cd (20 mumol/kg), or diethyl maleate (DEM, 5 mmol/kg), and tissue MT concentrations were measured 24 hr later. MT-TG mice responded to MT inducers in a manner similar to control mice. The hepatic antioxidant components (glutathione (GSH), GSH-peroxidase, GSH-reductase, GSH S-transferase, superoxide dismutase, DT-diaphorase, and catalase) of MT-TG mice were not different from those of controls. The cytochrome P450 enzymes (total P450, b5, NADPH cytochrome c reductase) were normal in these MT-TG mice. The activities of CYP1A, CYP2B, and CYP2E enzymes in MT-TG mice were also similar to those of controls, as determined by ethoxy- and pentoxyresorufin O-dealkylation and chlorzoxazone 6-hydroxylation. Thus, MT-TG mice appear to be a good model for studying functions of MT.
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PMID:Characterization of metallothionein-I-transgenic mice. 764 27

The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG), the glutathione reductase catalysed reaction (GSSG-->2GSH), or both. Neonatal rat heart cell cultures were subjected to a standardized protocol of oxidative stress using 80 mumol.l-1 cumene hydroperoxide (CHPO) for 0-90 min. The consequences of this protocol were described in terms of cellular concentrations of GSH, GSSG, NADPH and ATP, formation of malondialdehyde (MDA), release of GSSG and of ATP catabolites, depression of contraction frequency, cellular calcium overload, and enzyme release. Trolox-C, an analogue of vitamin E, accelerated the glutathione peroxidase reaction leading to lowering of GSH concentration and the GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, delayed calcium overload, and less enzyme release. Glucose was used to accelerate the glutathione reductase reaction by supplying NADPH, leading to higher GSH concentration and a higher GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, unchanged development of calcium overload, and less enzyme release. As a full turn of the glutathione redox cycle involves both the peroxidase and the reductase reactions, the combination of Trolox-C and glucose was superior to either of the two alone: 90 min following addition of CHPO together with Trolox-C and glucose, the GSH concentration and the GSH/GSSG ratio were almost normal, MDA formation was extremely low, calcium overload was markedly delayed, and enzyme release hardly occurred at all. Cells remained beating in the observation period of 30 min. We conclude that the capacity of the glutathione redox cycle to withstand oxidative stress can be increased by stimulation of either the peroxidase reaction or the reductase reaction, and that optimal redox cycling is achieved by stimulation of both reactions.
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PMID:Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle. 767 3

Activity of the antioxidation enzymatic system, involving evaluation of glutathione-reductase, -peroxidase and -S-transferase as well as glucose-6-phosphate dehydrogenase activities, was studied in blood plasma, leukocytes, lymphocytes and erythrocytes of patients with benign symmetric lipomatosis. Elevation in the rate of lipid peroxidation induced the antioxidation enzymatic system and caused a imbalance of its individual units. Intensive antioxidation therapy using "Aevit" allowed correction of the imbalance observed in the enzymatic activity.
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PMID:[Status of the antioxidant enzyme system in benign symmetrical lipomatosis and changes in it from the use of antioxidant therapy]. 777 Oct 93

Using ESR, a weak signal identified as the ascorbate free radical was observed in fresh cow's milk. The signal was unchanged after storage at 5 degrees C for 24 h but disappeared after storage at 25 degrees C. A marked increase in the steady-state ascorbate radical concentration was observed with the addition of H2O2 or xanthine; the increase was abolished in the presence of azide. Based on the xanthine-oxygen reductase activity and 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulfonic acid) peroxidase activity, cow's milk contains 0.45 microM xanthine oxidase and 0.32 microM lactoperoxidase. The results suggest that H2O2- and xanthine-induced ascorbate radical formation was due to the ascorbate peroxidase activity of lactoperoxidase in cow's milk.
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PMID:Ascorbate radicals in fresh cow's milk. 785 81

The sensitivity of the microaerophilic protozoan Trichomonas vaginalis to oxygen and products of its reduction, and the antioxidant defences employed by this organism, were investigated. Studies revealed that this amitochondrial flagellate is sensitive to oxygen tensions above those experienced in situ in the vagina (i.e. > 60 microM) and that metronidazole-resistant strains (CDC 85 and IR78) were more sensitive to elevated oxygen levels than a metronidazole-sensitive isolate (1910). In the presence of radical scavengers, inactivation of organisms at 60 microM oxygen was significantly lessened. Investigation of the antioxidant enzymes present in this organism revealed that activities of peroxide-reducing enzymes (e.g. catalase and general peroxidase) were not detectable, but that a cyanide-insensitive, azide-sensitive superoxide dismutase was present in cell extracts. Measurement of thiol-cycling enzymes indicated that NADPH could drive the reduction of oxidized glutathione (thiol reductase); however, the corresponding peroxidase activity was not detected. Analysis of thiols in whole cells of T. vaginalis indicated that glutathione was absent, but high levels of other thiols, propanethiol, methanethiol and H2S, were present. No significant differences were detected in thiol levels or antioxidant enzyme activities on comparison of metronidazole-sensitive and resistant strains. These results indicate that the sensitivity of T. vaginalis to oxygen above physiological levels is due to the lack of adequate peroxide-reducing enzymes and radical-scavenging mechanisms.
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PMID:Antioxidant defences in the microaerophilic protozoan Trichomonas vaginalis: comparison of metronidazole-resistant and sensitive strains. 795 98

A comprehensive study was performed on the brains of various vertebrate species showing different life energy potentials in order to find out if free radicals are important determinants of species-specific maximum life span. Brain superoxide dismutase, catalase, Se-dependent and independent GSH-peroxidases, GSH-reductase, and ascorbic acid showed significant inverse correlations with maximum longevity, whereas GSH, uric acid, GSSG/GSH, in vitro peroxidation (thiobarbituric acid test), and malondialdehyde (measured by HPLC), did not correlate with maximum life span. Superoxide dismutase, catalase, GSH-peroxidase, GSH and ascorbate results agree with those previously reported in various independent works using different animal species. GSSG/GSH, and true malondialdehyde (HPLC) results are reported for the first time in relation to maximum longevity. The results suggest that longevous species simultaneously show low antioxidant concentrations and low levels of in vivo free radical production (a low free radical turnover) in their tissues. The "free radical production hypothesis of aging" is proposed: a decrease in oxygen radical production per unit of O2 consumption near critical DNA targets (mitochondria or nucleus) increases the maximum life span of extraordinarily long-lived species like birds, primates, and man. Free radical production near these DNA sites would be a main factor responsible for aging in all the species, in those following Pearl's (Rubner's) metabolic rule as well as in those not following it.
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PMID:A decrease of free radical production near critical targets as a cause of maximum longevity in animals. 795 69

Escherichia coli strains were previously found to be susceptible to the antituberculosis drug isonicotinic acid hydrazide (isoniazid [INH]) when they carried certain mutations that also sensitize them to peroxides: a deletion in oxyR, a redox-sensitive regulator of hydrogen peroxide-inducible genes, or mutations in both katG and ahpCF, OxyR-regulated genes encoding hydroperoxidase I, and an alkyl hydroperoxide reductase. To test whether INH, like peroxides, activates OxyR, the effect of INH on OxyR regulation was examined. Primer extension assays showed that transcription of the OxyR-regulated oxyS gene was not significantly induced by INH in wild-type cells, indicating that INH does not activate OxyR. However, the INH-susceptible katG ahpCF mutant strain was found to have constitutively high levels of oxyS transcription. This suggested that the lack of peroxidase expression in these strains allows endogenous oxidants to accumulate, and this leads not only to constitutive OxyR activation but also to INH susceptibility. Consistent with this concept, hydrogen peroxide or cumene hydroperoxide potentiated the INH susceptibilities of wild-type cells, while the antioxidant ascorbic acid protected the susceptible katG ahpCF mutant strain from INH. Superoxide radicals, generated by paraquat, did not enhance the INH susceptibilities of wild-type cells. Hydrogen peroxide also potentiated the INH susceptibilities of susceptible and resistant (katG mutant) Mycobacterium smegmatis strains. Our results suggest that INH is converted to a more active drug by reaction with peroxides and that the INH susceptibilities of enterobacteria and mycobacteria are mechanistically related.
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PMID:Effects of peroxides on susceptibilities of Escherichia coli and Mycobacterium smegmatis to isoniazid. 798 15

It is well known that reperfusion damage of ischemic myocardium may be attributed to alterations in the antioxidant defense system against free radical aggression. In addition, the degree of myocardial damage may depend on the duration and severity of ischemia that precedes reperfusion. We carried out serial ischemic experiments (10, 30, 60 and 120 min) in ex-vivo rat hearts followed by 30 min reperfusion and we assayed the glutathione-dependent enzymatic activities (selenium-dependent glutathione-peroxidase: GSH-Px; selenium-independent glutathione peroxidase: GST-Px; glutathione-transferase: GST and glutathione-reductase: GS-SG-Red), Catalase activity (CAT) and non-proteic thiol compounds (NP-SH) at the end of reperfusion. We found a significant reduction of NP-SH, GSH-Px and CAT in ischemic/reperfused hearts from 30 min on, while GST activity was increased. In addition, we observed the appearance of a selenium-independent glutathione peroxidase activity (GST-Px) belonging to the GST system. In conclusion, we found the longer the duration of ischemia the greater the inbalance between the myocardial antioxidant system especially the GST activation, suggesting in particular for GST-Px, a role in the control of the damage against oxygen toxicity during ischemia/reperfusion.
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PMID:Myocardial antioxidant defense mechanisms: time related changes after reperfusion of the ischemic rat heart. 801 40

Several biochemical and functional modifications demonstrated in goitrous tissues could reflect the effect of goitrogenic factors. Growth-enhancing agents, including TSH itself, have been involved in goitrogenesis. To study comparatively the variation patterns of some TSH-dependent enzymes within single goitrous tissues, we measured the activities of peroxidase (TPO), NADPH-cytochrome-c (cyt-c) reductase, and monoamine oxidase (MAO) in tissues from cold follicular adenoma and multinodular goiter. Iodide transport and organification were also evaluated. Perinodular and necropsy tissues were used as controls. The mean TPO activity measured by guaiacol as well as triiodide assays was significantly increased in multinodular goiter, whereas a nonsignificant increment was observed in cold adenoma. NADPH-cyt-c reductase and MAO were markedly increased in the two types of pathological tissues. The individual activities of the three enzymes showed dissimilar modifications within single samples and among different tissues. There was no correlation in the activities of the enzymes within single specimens from cold adenoma and multinodular goiter, except for MAO and NADPH-cyt-c reductase in multinodular goiter, for which a significant correlation was obtained. In this tissue, MAO and TPO measured by guaiacol assay were weakly correlated. TPO activity evaluated by guaiacol oxidation was correlated with that measured by triiodide formation in cold adenoma, but not in multinodular goiter. The mean iodide organification values assayed by iodotyrosine formation in the absence of exogenous H2O2 in particulate fractions from cold adenoma and multinodular goiter were within the normal range. A reduced iodide transport, evaluated as the thyroid/medium ratio, was observed in slices from these tissues. The dissociation of the three enzyme activities in single specimens from cold adenoma and multinodular goiter along with the reduced iodide transport in these tissues support the hypothesis that factors other than TSH or with TSH-like effects could be involved in the abnormal thyroid growth.
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PMID:Dissociation of thyrotropin-dependent enzyme activities, reduced iodide transport, and preserved iodide organification in nonfunctioning thyroid adenoma and multinodular goiter. 802 49


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