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)

Recently there has been growing interest in magnesium deficiency and its correlation with coronary artery disease, chronic complications of diabetes mellitus and antioxidant enzyme activity. Hypomagnesemia is a common association of diabetes mellitus, and the blood glutathione (GSH) level is significantly lower in both conditions. Metformin (Met), 'an oral antihyperglycemic drug' frequently used in the management of diabetes mellitus outside the USA, has been shown to have an insulin-like action. The purpose of this study was to investigate the effect of oral administration of Met (60 mg kg(-1)) for 14 days on GSH and magnesium levels in blood, liver and heart of normal and streptozotocin-induced diabetic Wistar rats. Diabetes was induced by an i.p. injection of streptozotocin (60 mg kg(-1)). Our results showed that Met did not affect fasting serum glucose concentration in non-diabetic animals but reduced it significantly in diabetic animals. Serum and liver magnesium levels were significantly decreased in the untreated diabetic group compared with the normal group. Treatment with Met improved liver magnesium concentration in the diabetic group only. It has no effect on serum magnesium in diabetic or non-diabetic rats. Heart magnesium levels showed non-significant changes in all groups. In diabetic animals a significant decrease of GSH in both blood and liver was observed. Treatment with Met increased these levels significantly, with a similar effect on GSH levels in non-diabetic rats. There were no significant changes in heart GSH levels in any of the groups. This study demonstrates that oral Met therapy improves the altered levels of magnesium and GSH in diabetic rats.
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PMID:Effect of metformin on glutathione and magnesium in normal and streptozotocin-induced diabetic rats. 866 22

The influences of food deprivation and refeeding on glutathione (GSH) status, antioxidant enzyme activity and lipid peroxidation in response to an acute bout of exercise were investigated in the liver and skeletal muscles of male Sprague-Dawley rats randomly divided into three groups: starved for 48 h without refeeding; starved for 48 h and refed for 24 or 48 h. Half of each group of rats was exercised on a treadmill until exhaustion and killed immediately, whereas the other half group was killed at rest. Food-deprived rats had significantly lower liver GSH concentration and GSH:glutathione disulfide (GSSG) ratio. Malondialdehyde concentrations in the liver and skeletal muscle were both higher in the starved than in the refed rats (P < 0.05). Refed rats had significantly greater liver GSH level, gamma-glutamylcysteine synthetase and glucose 6-phosphate dehydrogenase activities and plasma insulin concentration than unfed rats. Exercised 24- and 48-h refed rats had 27% and 31 % lower liver GSH (P < 0.05), respectively, and a 21 % lower GSH:GSSG ratio (P < 0.05) than their rested counterparts. Plasma insulin concentrations were significantly lower, whereas glucagon concentrations were greater in the exercised than in the rested rats. Muscle GSH concentration was significantly lower in the food-deprived than in the refed rats (P < 0.05) but was unaffected by exercise. Exercised 24-h refed rats had significantly elevated muscle GSSG concentration compared with rested rats, along with a higher GSH peroxidase and a lower gamma-glutamyltranspeptidase activity (P < 0.05). These data indicate that both food deprivation-refeeding and exhaustive exercise influence liver and skeletal muscle glutathione status and that these changes may be controlled by hepatic glutathione synthesis and release due to hormonal stimulation.
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PMID:Alteration of glutathione and antioxidant status with exercise in unfed and refed rats. 868 45

The authors studied the effect of alpha-tocopherol acetate and nicotinamide on lipid peroxidation and antioxidant enzyme defense (AED) in red cell membranes of 61 patients with new-onset insulin-dependent diabetes mellitus. Lipid peroxidation products were found in excessive quantities, whereas enzymes of the cell antioxidant defense were on the decrease. Combination of tocopherol with nicotinamide as adjuvants to conventional insulin therapy promoted normalization of lipid peroxidation and AED, improving beta-cell function. It is believed justified to introduce antioxidant treatment early in the disease onset to prevent toxic damage to beta-cells and vascular endothelium induced by lipid peroxidation products.
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PMID:[Treatment with thymogen and myelopid of patients with bronchial asthma]. 869 81

This study examined the effects of glycocorticoids, insulin, thyroxine, and epinephrine upon the activities of CuZn- and Mn-superoxide dismutases (SOD), catalase, and glutathione peroxidase (GPX) and upon hydrogen peroxide production in rat macrophages obtained from the intraperitoneal cavity. The experiments were performed in vivo under conditions causing hormonal dysfunctions: adrenal demedullation, dexamethasone treatment, thyroidectomy, administration of L-tri-iodothyronine (T3) and L-thyroxine (T4), and diabetes. Macrophages were also cultured for 24 hr in the presence of dexamethasone, thyroid hormones, and insulin as to evaluate possible interferences caused in vivo by changes in other hormones. The results indicated that these hormones do control the activities of the antioxidant enzymes and hydrogen peroxide production both in vivo and in vitro. Insulin increased the activities of CuZn-SOD, catalase, and GPX and reduced that of Mn-SOD. Thyroid hormones raised the activities of CuZn- and Mn-SOD and decreased that of GPX, whereas glucocorticoids reduced both Mn-SOD and GPX. The removal of the adrenal medulla caused a decrease of Mn-SOD and GPX activities in the macrophages. Hydrogen peroxide production was increased by insulin and reduced by thyroid hormones and glucocorticoids. The changes in antioxidant enzyme activities caused by these hormones in macrophages may indicate important mechanisms for the establishment of impaired immune function in endocrine pathologies.
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PMID:Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages. 884 37

Human thioredoxin reductase was recently shown to contain a TGA encoded selenocysteine residue at the penultimate position of its amino acid chain. Depending on the availability of selenium during biosynthesis, an authentic selenocysteine-containing or a selenium-free enzyme truncated at the penultimate position is expected to be formed. Correspondingly, the enzymatic activity should be altered by selenium restriction, if the selenocysteine residue is functionally important. In order to check the catalytic role of the selenocysteine residue, four different human cell lines were grown in selenium deficient media or with adequate selenium supplementation (40 nM sodium selenite) and thioredoxin reductase activity was measured as NADPH-dependent DTNB reduction or thioredoxin-mediated insulin reduction. Thioredoxin reductase activities, like glutathione peroxidase activities, were consistently higher in selenium supplemented cells, whereas glutathione reductase activity was not affected by the selenium. The dose-response was similar for thioredoxin reductase and glutathione peroxidase, but the recovery of glutathione peroxidase activity upon selenium supplementation was faster than with thioredoxin reductase. Also the increase of glutathione peroxidase activities was substantially higher than that of thioredoxin reductase (400-1200% versus a maximum of 250%). These observations clearly indicate a catalytic role of the selenocysteine residue in the thioredoxin reductase, but suggest either the existence of a selenium-unresponsive isoenzyme or a residual disulfide reductase activity in the selenium-free truncated protein made under conditions of selenium deficiency.
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PMID:Evidence for a functional relevance of the selenocysteine residue in mammalian thioredoxin reductase. 928 5

Antioxidant enzyme expression was determined in rat pancreatic islets and RINm5F insulin-producing cells on the level of mRNA, protein, and enzyme activity in comparison with 11 other rat tissues. Although superoxide dismutase expression was in the range of 30% of the liver values, the expression of the hydrogen peroxide-inactivating enzymes catalase and glutathione peroxidase was extremely low, in the range of 5% of the liver. Pancreatic islets but not RINm5F cells expressed an additional phospholipid hydroperoxide glutathione peroxidase that exerted protective effects against lipid peroxidation of the plasma membrane. Regression analysis for mRNA and protein expression and enzyme activities from 12 rat tissues revealed that the mRNA levels determine the enzyme activities of the tissues. The induction of cellular stress by high glucose, high oxygen, and heat shock treatment did not affect antioxidant enzyme expression in rat pancreatic islets or in RINm5F cells. Thus insulin-producing cells cannot adapt the low antioxidant enzyme activity levels to typical situations of cellular stress by an upregulation of gene expression. Through stable transfection, however, we were able to increase catalase and glutathione peroxidase gene expression in RINm5F cells, resulting in enzyme activities more than 100-fold higher than in nontransfected controls. Catalase-transfected RINm5F cells showed a 10-fold greater resistance toward hydrogen peroxide toxicity, whereas glutathione peroxidase overexpression was much less effective. Thus inactivation of hydrogen peroxide through catalase seems to be a step of critical importance for the removal of reactive oxygen species in insulin-producing cells. Overexpression of catalase may therefore be an effective means of preventing the toxic action of reactive oxygen species.
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PMID:Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. 935 19

Impaired antioxidant defences may predispose to the increased resting and exercise-induced oxidative stress found in patients with insulin-dependent diabetes mellitus (IDDM). We investigated major erythrocyte antioxidant enzyme activities at rest and in response to sustained, moderate intensity physical exercise in young diabetic men (n = 9) previously reported to have markedly elevated plasma lipid peroxidation and blood glutathione levels compared with control men (n = 13) (Laaksonen et al. 1996). At rest, erythrocyte glutathione reductase activity was 15% higher in the diabetic group (P = 0.049). Se-glutathione peroxidase and glutathione-S-transferase activities were similar in both groups. Red cell Cu, Zn-superoxide dismutase and catalase activities were lower in the IDDM group (P = 0.033 and P = 0.023, respectively). After 40 min of exercise at 60% of the subjects' peak oxygen consumption, Se-glutathione peroxidase activity rose by about 14% in the control group (P = 0.003), but not in the IDDM group (P = 0.47). Exercise did not cause significant changes in other enzyme activities in either group. To conclude, lower erythrocyte Cu, Zn-superoxide dismutase and catalase activity in young men with IDDM at rest may contribute to increased oxidative stress. On the other hand, increased glutathione reductase activity may represent a compensatory upregulation of glutathione homeostasis in response to increased oxidative stress. Upregulation of Se-glutathione peroxidase activity in response to physical activity appeared to be impaired in men with IDDM.
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PMID:Altered antioxidant enzyme defences in insulin-dependent diabetic men with increased resting and exercise-induced oxidative stress. 936 62

Oxidative stress is involved in aging and age-related diseases. Several metabolic alterations similar to those encountered with aging and age-related diseases have been observed in response to hyperinsulinemia. Surprisingly, this metabolic derangement diminished hepatic peroxisomal beta-oxidation which is a major source of H2O2 production in the liver, suggesting a protective effect against oxidative stress. However, the impact of hyperinsulinemia on the balance between H2O2 production and elimination in the liver is not known. Consequently, this study was undertaken to evaluate the effect of sustained high serum insulin levels on the activity of hepatic catalase, a peroxisomal antioxidant enzyme involved in the decomposition of H2O2. Male Sprague-Dawley rats received intravenous infusion of either 30% glucose, 30% galactose or normal saline for seven days. Activity of hepatic peroxisomal beta-oxidation and catalase decreased 58% and 74%, respectively, in glucose-infused rats compared with galactose- or saline-infused animals. When infused simultaneously with glucose, diazoxide blocked glucose-enhanced insulin secretion and prevented the decrease in peroxisomal enzyme activities, without altering blood glucose concentration. Neither diazoxide alone nor galactose, which did not alter serum insulin levels, had any effect on enzyme activities. These results suggest that hyperinsulinemia is responsible for the decreased enzyme activities observed in glucose-infused rats. Indeed, a strong negative correlation between serum insulin levels and hepatic peroxisomal enzyme activities was found. To investigate the mechanism by which insulin modulates catalase activity, we studied rates of synthesis and degradation of catalase in saline- and glucose-infused rats. Data show that insulin diminishes rates of catalase synthesis, while exhibiting no effect on its degradation. Upsetting the balance between the cellular capacity to produce and eliminate H2O2 may be a contributing factor to the known deleterious effects of hyperinsulinemia.
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PMID:Enhanced potential for oxidative stress in hyperinsulinemic rats: imbalance between hepatic peroxisomal hydrogen peroxide production and decomposition due to hyperinsulinemia. 1033 85

Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.
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PMID:An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. 1033 13

Reactive oxygen species play an important role in the cytotoxic effect of inflammatory cytokines on pancreatic beta-cells in type 1 diabetes mellitus. The antioxidant enzyme manganese superoxide dismutase (MnSOD) is part of the cellular defenses against these deleterious radicals. MnSOD gene expression is induced by cytokines in insulin-producing cells, but the transcriptional regulation of MnSOD expression in these cells is not well understood. In this report, we investigated the transcriptional regulation by cytokines of the rat MnSOD gene in insulin-producing cells. By transient transfections with promoter-luciferase reporter constructs, we identified two interleukin (IL)-1beta-responsive elements, conferring each an additive 3-fold IL-1beta-induced transcriptional activity. The first is located in the promoter region, whereas the second is located in the second intron of the MnSOD gene. Interestingly, the intronic element is required for interferon-gamma-induced potentiation. Site-directed mutagenesis and band-shift assays showed that an NF-kappaB binding site in each region is necessary, but not sufficient, for transcriptional induction by IL-1beta. Our results suggest that NF-kappaB may cooperate with CCAAT/enhancer-binding protein factors in the promoter region and with octamer and Ets factors in the intronic region.
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PMID:NF-kappaB is required for cytokine-induced manganese superoxide dismutase expression in insulin-producing cells. 1061 34


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