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)

Associated with amiodarone (AM) therapy is pneumonitis, which may progress to life-threatening pulmonary fibrosis. Although the etiology of amiodarone-induced pulmonary toxicity (AIPT) is unknown, a role for direct toxicity by oxidative stress has been proposed. We have used a single intratracheal administration of AM (1.8 mg (2.64 mumol)) to male golden Syrian hamsters to investigate the role of oxidative stress in AIPT. The antioxidant capacity of the lung was assessed following AM administration by evaluating glutathione status and antioxidant enzyme activities. The efficacy of treatment with the antioxidant agents butylated hydroxyanisole, diallyl sulfide, and N-acetylcysteine, in attenuation of AM-induced pulmonary fibrosis was also investigated. AM significantly (p < 0.05) increased the ratio of oxidized to total lung glutathione both 30 min (control, 0.93 +/- 0.23%; AM, 2.06 +/- 0.26%) and 120 min (control, 0.90 +/- 0.21%; AM, 3.58 +/- 1.34%) post administration. AM also increased activities of glutathione reductase (by 89%) 3 days post administration, and glutathione peroxidase (by 110 and 45%, respectively) and total superoxide dismutase (by 58 and 35%, respectively) both 3 and 7 days post administration. However, treatment of hamsters with butylated hydroxyanisole (150 mg.kg-1.day-1 s.c.) or diallyl sulfide (200 mg.kg-1.day-1, p.o.) for 3 days prior to AM, or treatment with N-acetylcysteine (10 mg intratracheally) 10 min prior to AM had no effect on pulmonary fibrosis 21 days post treatment, as determined by lung wet weight and hydroxyproline content, and had inconsistent effects on histologically determined disease index.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Investigation of the role of oxidative stress in amiodarone-induced pulmonary toxicity in the hamster. 795 92

Glutathione (GSH) content and antioxidant enzyme activities were investigated in skeletal muscle of young, adult, and old male Fischer 344 rats. Furthermore, the effect of 10 wk of exercise training on these antioxidant systems was evaluated at all ages. In the soleus muscle, GSH concentration increased markedly with age, with no significant change in glutathione disulfide (GSSG) content. Training caused a 30% decrease of GSH (P < 0.05) in the soleus of young rats and a reduction of the GSH-to-GSSG ratio at all ages. Activity of gamma-glutamyl transpeptidase (GGT), a key enzyme for GSH uptake by muscle, was also significantly decreased with training. GSH, GSSG, and the GSH-to-GSSG ratio were not altered with aging or training in the deep portion of vastus lateralis muscle (DVL). Activities of GSH peroxidase (GPX), GSSG reductase (GR), superoxide dismutase (SOD), catalase (CAT), and GSH sulfur-transferase were increased significantly with aging in both soleus and DVL. In DVL, training increased GPX and SOD activities in the young rats, whereas in soleus, training decreased GR and CAT activities in the adult rats and GGT and CAT activities in the old rats. Muscle lipid peroxidation was significantly increased with aging in both DVL and soleus but was not affected by training. These data indicate that aging may cause not only an overall elevation of antioxidant enzyme activities but also a fiber-specific adaptation of GSH system in skeletal muscle. Exercise training, although increasing selective antioxidant enzymes in the young rats, does not offer additional protection against oxidative stress in the senescent muscle.
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PMID:Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems. 806 52

The effect of mercury as Hg2Cl2 and HgCl2 on the antioxidant enzyme levels and its toxicity was investigated in an insect model comprised of adult females of the common housefly, Musca domestica, and fourth-instar larvae of the cabbage looper moth, Trichoplusia ni. HgCl2 was found to be more toxic than Hg2Cl2 to both M. domestica and T. ni. The LC50s for M. domestica were 1.17% and 0.38% w/v concentration for Hg2Cl2 and HgCl2, respectively. For the more tolerant T. ni, the LC50S were 5.15% for Hg2Cl2 and 0.96% w/w concentration for HgCl2. The minimally acute LC5 dose of both oxidation states of Hg was approximately 0.005% for both insects (w/v for M. domestica and w/w for T. ni). At the LC5, both forms of Hg significantly induced the activity of superoxide dismutase in both insect species. Catalase was induced by both Hg2Cl2 and HgCl2 in M. domestica but was only induced by HgCl2 in T. ni. Glutathione-S-transferase, its peroxidase activity, and glutathione reductase activities were also significantly altered in most cases by Hg in both insects although the pattern of alternation was different between the two insects. It is evident that mercury induces oxidative stress in insects as it does in vertebrates. Our findings suggest that insects may serve as a valuable, non-mammalian model species to assess Hg-induced oxidative stress as a component of environmental toxicity.
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PMID:An insect model for assessing mercury toxicity: effect of mercury on antioxidant enzyme activities of the housefly (Musca domestica) and the cabbage looper moth (Trichoplusia ni). 811 20

The crystal structures of three forms of Escherichia coli thioredoxin reductase have been refined: the oxidized form of the wild-type enzyme at 2.1 A resolution, a variant containing a cysteine to serine mutation at the active site (Cys138Ser) at 2.0 A resolution, and a complex of this variant with nicotinamide adenine dinucleotide phosphate (NADP+) at 2.3 A resolution. The enzyme mechanism involves the transfer of reducing equivalents from reduced nicotinamide adenine dinucleotide phosphate (NADPH) to a disulfide bond in the enzyme, via a flavin adenine dinucleotide (FAD). Thioredoxin reductase contains FAD and NADPH binding domains that are structurally similar to the corresponding domains of the related enzyme glutathione reductase. The relative orientation of these domains is, however, very different in the two enzymes: when the FAD domains of thioredoxin and glutathione reductases are superimposed, the NADPH domain of one is rotated by 66 degrees with respect to the other. The observed binding mode of NADP+ in thioredoxin reductase is non-productive in that the nicotinamide ring is more than 17 A from the flavin ring system. While in glutathione reductase the redox active disulfide is located in the FAD domain, in thioredoxin reductase it is in the NADPH domain and is part of a four-residue sequence (Cys-Ala-Thr-Cys) that is close in structure to the corresponding region of thioredoxin (Cys-Gly-Pro-Cys), with a root-mean-square deviation of 0.22 A for atoms in the disulfide bonded ring. There are no significant conformational differences between the structure of the wild-type enzyme and that of the Cys138Ser mutant, except that a disulfide bond is not present in the latter. The disulfide bond is positioned productively in this conformation of the enzyme, i.e. it stacks against the flavin ring system in a position that would facilitate its reduction by the flavin. However, the cysteine residues are relatively inaccessible for interaction with the substrate, thioredoxin. These results suggest that thioredoxin reductase must undergo conformational changes during enzyme catalysis. All three structures reported here are for the same conformation of the enzyme and no direct evidence is available as yet for such conformational changes. The simplest possibility is that the NADPH domain rotates between the conformation observed here and an orientation similar to that seen in glutathione reductase. This would alternately place the nicotinamide ring and the disulfide bond near the flavin ring, and expose the cysteine residues for reaction with thioredoxin in the hypothetical conformation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Crystal structure of Escherichia coli thioredoxin reductase refined at 2 A resolution. Implications for a large conformational change during catalysis. 811 95

It has been suggested that oxidative processes are involved in a variety of pathological conditions, notably ischemia-reperfusion injury. Moreover, anesthetics appear to exert differential effects on the severity of such injury, these being unlikely wholly attributable to their differential effects on cardiovascular or microcirculatory status. It is possible that these variable effects of anesthetics on this type of injury may be due, at least in part, to changes in the production of free radicals and/or in their detoxification by endogenous antioxidant enzymes. We have attempted to explore the latter possibility by measuring activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase in normal heart tissue and red cells obtained from rats anesthetized using a variety of agents (CO2, halothane, pentobarbital or ether). For comparison, analyses were also performed on tissues from unanesthetized animals rendered unconscious by stunning prior to sacrifice. Results indicated that myocardial SOD activity was significantly greater in halothane-anesthetized as compared with CO2-anesthetized animals. Red cell SOD activities did not show such differences. However, red cell GPX activity was found to be greater in halothane-anesthetized than in pentobarbital-anesthetized rats. In general, however, antioxidant enzyme activities measured ex vivo were minimally affected by the use of anesthetics prior to euthanasia. Our findings, therefore, do not support the proposal that the influence of anesthetics on the course of ischemia-reperfusion injury involves effects at the level of enzymatic antioxidant components.
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PMID:Effects of various anesthetic regimens on tissue antioxidant enzyme activities. 816 73

The toxicity of the antineoplastic agent doxorubicin (DOX) has been shown to be moderated by the antioxidant enzyme glutathione peroxidase. It has been reported that acute doses of DOX can cause an inhibition of glutathione peroxidase in cardiac tissue, that may render this tissue especially susceptible to further prooxidant damage. In this study, multiple DOX treatments at a therapeutic dose were assessed for their effect on the antioxidant enzyme status of cardiac and kidney tissue. DOX was administered i.p. (5 mg/kg) once a week for two weeks to male balb/c mice. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPOX) and glutathione reductase (GR) were measured 1, 2 and 7 days following the second DOX treatment in both heart and kidney. Levels of reduced glutathione (GSH) were also measured in cardiac tissue at these same times. Cardiac levels of GPOX and GR showed a time-dependent decrease in activity, with 10% and 12% inhibition for GPOX and GR, respectively, at 7 days post second treatment. Cardiac levels of GSH also showed a significant decrease, approximately 15%, at 7 days post second treatment. Cardiac levels of SOD and CAT as well as kidney levels of all four antioxidant enzymes were not affected by DOX treatment. These data suggest that DOX given in a therapeutic regimen, at a therapeutic dose, can cause decreases in cardiac levels of GPOX, GR and GSH that could render the heart especially susceptible to further oxidative challenge.
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PMID:Modulation of glutathione and glutathione dependent antioxidant enzymes in mouse heart following doxorubicin therapy. 822 37

Feeding diets depleted of vitamin E and Se to cattle can induce a disease known as nutritional degenerative myopathy. It is believed that an increased peroxidative challenge in muscle is involved in the pathogenesis of this disease. A number of species can up-regulate the activity of some antioxidant enzymes, including glutathione reductase (EC 1.6.4.2), glutathione transferase (EC 2.5.1.18), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), catalase (EC 1.11.1.6), and superoxide dismutase (EC 1.15.1.1), in an attempt to mitigate the effects of a peroxidative challenge. A 2 x 2 factorial study was set up to examine possible changes in the activities of these antioxidant enzymes in muscles of ruminant calves fed on diets low in either vitamin E or Se. Four groups of four calves each were fed on a basal diet of NaOH-treated barley which was supplemented with alpha-tocopherol or Se or both for a total of 50 weeks. Calves fed on diets depleted of vitamin E, but not those fed on diets low in Se, developed subclinical myopathy, as judged by increases in the activity of plasma creatinine kinase (EC 2.7.3.2), and had increased muscle concentrations of two indices of lipid peroxidation, namely thiobarbituric acid-reactive substances, with and without ascorbate activation. Feeding diets depleted of vitamin E and diets low in Se both increased muscle activities of glucose-6-phosphate dehydrogenase in heart, biceps and supraspinatus. This change may have occurred in an attempt to maintain intracellular pools of reduced glutathione. No other changes in antioxidant enzyme activity were observed.
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PMID:Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or selenium or both. 826 Apr 86

Normal embryonal mouse liver cells in culture were shown to undergo spontaneous transformation during prolonged subculture. The spontaneously transformed cells lost their anchorage dependence, as measured by a soft agar assay, and gave rise to tumors in nude mice. Accompanying this transformation, the antioxidant enzymes, copper- and zinc-containing superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione reductase, decreased significantly in activity; the decline in enzymatic activity of CuZnSOD, MnSOD and CAT was due to a decline in the levels of immunoreactive protein. These spontaneously transformed high passage in vitro liver cells appeared similar in morphology, antioxidant enzyme activity and tumorigenicity to their counterparts transformed by N-methyl-N-nitro-N-nitrosoguanidine and Simian virus 40. These data provide experimental evidence that changes in antioxidant enzymes are associated with spontaneous in vitro cellular transformation of mouse embryonal liver cells.
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PMID:Lowered antioxidant enzymes in spontaneously transformed embryonic mouse liver cells in culture. 833 Mar 64

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we investigated the change of antioxidant enzyme activities in a typical slow red muscle, the soleus. Atrophied soleus muscles were collected from male Wistar rats (16 weeks old), one ankle joint of which had been immobilized in the fully extended position for 7 days. Also, soleus muscles were collected from intact age-matched rats as control. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase (GST), catalase, and glutathione reductase (GSSGRx) were measured. The activities of Cu,Zn-SOD, GST, and GSSGRx were significantly higher in atrophied muscles, while the others were unchanged. Increased Cu,Zn-SOD and unchanged Mn-SOD levels might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. Owing to the enhancement of Cu,Zn-SOD and the unaltered Se-GSHPx and catalase activities, hydrogen peroxide is thought to be increased in the cytoplasm. Because there is also an increase of iron in the microsomes of atrophied muscles, the production of hydroxyl radicals, the most aggressive of radicals, might consequently be elevated.
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PMID:Antioxidant enzyme systems in skeletal muscle atrophied by immobilization. 843 91


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