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)

This hypothesis states that magnesium and copper (Cu) deficiency as well as high arterial oxygen pressure may contribute to the pathogenesis of retinopathy of prematurity (ROP), a major cause of blindness in very low birthweight preterm infants. Infants at highest risk have severe respiratory distress with hypoxia and require prolonged oxygen supplements. The retina is a multilayer sheet of neural tissue very rich in polyunsaturated fatty acids (PUFAs), oxygen, and mitochondria, with the highest oxygen consumption of all body tissues. Oxygen free radicals which are generated during metabolism cause lipid peroxidation of the PUFA-rich membranes, impairing retinal function. Magnesium and copper deficiencies provide less protection from oxidative injury which damages neurosensory tissue critical for photodetection. Protective antioxidant enzyme activity is reduced in magnesium and copper deficiency. There is some evidence for a raised level of vasoconstrictor thromboxane A2 (TXA2) in respect to vasodilator prostacyclin (PGI2), which would promote vasoconstriction. Deficiency of magnesium and of copper increase synthesis of TXA2 and decreases synthesis of PGI2. Sustained vasoconstriction leads to vascular occlusion, retinal ischaemia, reactive proliferation of retinal vasculature, and the final stages of ROP. Abundant magnesium and copper may protect the retina from developing ROP.
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PMID:Hypothesis: the possible role of magnesium and copper deficiency in retinopathy of prematurity. 884 91

To elucidate the role of oxygen-derived free radicals and superoxide dismutase in traumatic brain injury (TBI), blood-brain barrier (BBB) permeability, brain edema, behavioral function, and necrotic cavity volume (CV) were evaluated after TBI using nontransgenic (nTg) mice and heterozygous and homozygous transgenic (Tg) mice with a 1.5- (Tg 1.5x), 3.1-(Tg3.1x) and five- (Tg5x) fold increase in human copper, zinc-superoxide dismutase (CuZn-SOD) activity. Traumatic brain injury was produced by the weight-drop method. Evans blue dye leakage 4 hours after injury was attenuated in a CuZn-SOD dose-dependent manner with decreases of 18.6%, 40.9%, and 48.8%, in the Tg1.5x, Tg3.1x, and Tg5x groups, respectively. The water content 6 hours after injury in the Tg3.1x (79.64%) and Tg5x (79.45%) groups was significantly lower than in nTg mice (81.37%). There was an initial decrease in body weight and in motor performance, as measured by beam walk and beam balance tasks undertaken 1 day after TBI. However, the average reduction in beam balance and beam walk performance deficits and changes in body weight postinjury were significantly ameliorated in Tg mice. The CV was significantly smaller in Tg mice than in nTg mice (p < 0.01). These results indicate that superoxide radicals play a deleterious role following TBI. Furthermore, Tg mice provide a useful model for demonstrating the beneficial role of an antioxidant enzyme in TBI without the confounding effect of pharmacokinetics, toxicity, and BBB permeability associated with exogenous agents.
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PMID:Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice. 889 28

Oxidative stress has been postulated to contribute to the pathology associated with dietary copper deficiency. In vivo, erythrocytes are probable targets of oxidative damage because they are exposed to high concentrations of oxygen and contain heme iron that can autoxidize, which results in the formation of superoxide anions. Activity of the important antioxidant enzyme, copper, zinc superoxide dismutase, decreases markedly in erythrocytes during copper deficiency. The effect of dietary copper deficiency on indicators of oxidative stress was examined in erythrocyte membranes of rats maintained on a purified copper-deficient diet for 35 days after weaning. Erythrocytes were separated into young and old populations on a Percoll gradient prior to membrane isolation and quantification of lipid peroxides and protein carbonyls. Protein carbonyls, determined by Western blot immunoassay, were detected predominantly in both the alpha and beta chains of spectrin. Alpha and beta subunits of spectrin in erythrocyte membranes from copper-deficient rats contained higher amounts of carbonyls than controls, regardless of the population of erythrocytes studied. This study suggests that spectrin may be a specific target for oxidative damage when erythrocyte copper, zinc superoxide dismutase activity is reduced by copper deficiency.
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PMID:In vivo oxidative modification of erythrocyte membrane proteins in copper deficiency. 911 52

The major cause of death following transplantation is cardiovascular disease. Among the many processes involved in atherogenesis, oxidative stress and modification of low density lipoprotein has been assigned a major role. This in turn may be affected by the immunosuppressive regime used. We studied oxidative stress in 40 renal transplant patients receiving two different immunosuppressive regimens (20 on cyclosporin, 20 on azathioprine/prednisolone), and 19 normal controls. Changes in lipid peroxidation (assessed as thiobarbituric acid reacting substances, TBARS), antioxidant enzyme activities (glutathione reductase GSHPx, glutathione peroxidase GSHPx and superoxide dismutase SOD) vitamin E and antioxidant associated trace metals (selenium, copper, zinc) were studied. Alteration of erythrocyte membrane fluidity was examined using the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene (DPH). Both transplant groups showed no difference in TBARS, lipid standardised vitamin E, copper or selenium compared to controls. Zinc was significantly increased in both the cyclosporin and azathioprine groups compared to controls (P < 0.05). SOD was reduced in both transplant groups compared to controls (P < 0.001). GSHPx was elevated in both groups compared to controls but only reached significance in the azathioprine treated group (P < 0.005). GSHRx was slightly elevated in both transplant groups but did not reach significance. Erythrocyte membrane anisotropy was decreased in the cyclosporin treated group (P < 0.05). There was no difference in the azathioprine group compared to controls. The present results suggest an adaptive response to increased oxidative stress in both transplant groups sufficient to minimise markers of oxidative stress (TBARS and anisotropy). The results also suggest no significant difference between the two immunosuppressive regimes with regard to oxidative stress.
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PMID:Oxidative stress in cyclosporin and azathioprine treated renal transplant patients. 926 98

It has been suggested that high iron stores enhance colon carcinogenesis. The effect of high dietary iron (Fe) on indices of iron, copper (Cu) and manganese (Mn) status, lipid peroxidation using the thiobarbituric acid reactive substances assay, superoxide dismutase, glutathione peroxidase, glutathione transferase and ceruloplasmin activities, cell proliferation and development of preneoplastic lesions known as aberrant crypt foci (ACF) in rat colon was examined using a 3 x 2 factorial design. Male weanling Sprague-Dawley rats were fed adequate (AFe; 45 mg Fe/kg diet), moderately high (MHFe; 225 mg Fe/kg diet) and high (HFe; 450 mg Fe/kg diet) dietary Fe for 2.5 wk, then treated with azoxymethane (AOM; 2 injections, 1 wk apart; total dose 30 mg/kg body weight) or saline (n = 14-15 per group). Dietary treatment continued for another 6 wk after the second AOM dose. At the time of AOM injection, colon Fe concentrations were one- and threefold higher for MHFe and HFe rats, respectively, than for AFe rats. It was proposed that high dietary Fe would adversely affect Cu and Mn status, resulting in impaired antioxidant enzyme activity. However, neither indices of Cu and Mn status nor colonic mucosal antioxidant enzyme activities were affected by dietary Fe except for plasma ceruloplasmin activity, which was slightly lower in rats fed high iron diets than in rats fed adequate iron diets (P < 0.01). Dietary Fe had no significant effect on colonic mucosal lipid peroxidation, cell proliferation or ACF development. In conclusion, our findings suggest that dietary Fe concentrations that are approximately 5 and 10 times adequate do not enhance oxidative stress, cell proliferation and ACF development in the colon of rats.
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PMID:Iron supplementation does not affect cell proliferation or aberrant crypt foci development in the colon of sprague-dawley rats. 952 41

This study investigated whether differences in the prevalence and severity of coal workers' pneumoconiosis (CWP) between three coal mines could be related to differences in oxidative stress exposure as evaluated in vivo through red-blood-cell antioxidant enzyme activities. Blood samples were obtained from 229 miners selected according to their occupation and their pneumoconiotic status. The following biomarkers were evaluated: erythrocyte catalase, Cu2+/Zn2+ superoxide dismutase (Cu2+/Zn2+ SOD), and glutathione peroxidase activities. Antioxidant enzyme activities did not differ significantly between the group of surface workers in Lorraine and the group of underground miners without CWP in Lorraine and in the other coal mines. Erythrocyte Cu2+/Zn2+ SOD activity was slightly decreased in the group of active underground miners with simple pneumoconiosis as compared with the group of miners without CWP in Nord/Pas-de-Calais. No effect was seen between retired miners at different stages of CWP. Our findings indicate that differences in the prevalence and severity of CWP do not seem to be related to various oxidative activities of coal dust particles, at least as reflected by measurements of antioxidant enzyme activities in circulating erythrocytes in this study.
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PMID:Erythrocyte antioxidant enzyme activities in coal miners from three French regions. 963 82

The response of endogenous antioxidants to acute exposure of the mitochondrial inhibitor, 3-nitropropionic acid (3-NPA), was investigated in selected rat brain regions. Rats treated with 3-NPA (30 mg/kg, s.c.) were sacrificed at 30, 60, 90 and 120 min after injection to examine the alterations in reduced glutathione levels (GSH), and activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus (HIP), frontal cortex (FC), and caudate nucleus (CN). CAT activity increased in the HIP 90 min after 3-NPA treatment. While cytosolic copper/zinc SOD (CuZn-SOD) and mitochondrial manganese SOD (Mn-SOD) levels increased in the FC at 120 min, only the Mn-SOD increased in the CN 90 min after treatment. The activity of GPx decreased in the HIP 120 min after 3-NPA injection. When compared with the control, administration of 3-NPA led to GSH depletion in HIP within 120 min. The depletion of GSH and induction of antioxidant enzyme activities after the 3-NPA exposure suggest conditions favorable for oxidative stress.
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PMID:Effect of acute exposure to 3-nitropropionic acid on activities of endogenous antioxidants in the rat brain. 972 71

CuZn superoxide dismutase (CuZn SOD) is one of several antioxidant enzymes that defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding CuZn SOD are found in patients with familial amyotrophic lateral sclerosis (FALS), a progressive and fatal paralytic disease that is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease can be reproduced in transgenic mice by expression of mutant human CuZn SOD. Recent studies both in vitro and in vivo suggest that the effect of mutation is to enhance the generation of oxygen radicals by the mutant enzyme. Thus, mutation converts a protective, antioxidant enzyme into a destructive, prooxidant form that catalyses free radical damage to which motor neurons are selectively vulnerable. Recent studies of neuroprotective agents in the FALS model show that inhibition of oxidative mechanisms (copper chelation therapy, dietary antioxidants, and coexpression of bcl-2) delays disease onset but does not extend disease duration. In contrast, inhibition of glutamatergic or apoptotic mechanisms (riluzole, gabapentin, and coexpression of glutamatergic or apoptotic mechanisms (riluzole, gabapentin, and coexpression of an inhibitor of caspase-1) has no effect on disease onset but extends survival by increasing the duration of symptomatic disease. Thus, neuroprotective agents differentially target the processes underlying disease initiation and propagation.
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PMID:Mutant CuZn superoxide dismutase in motor neuron disease. 972 38

Copper-zinc superoxide dismutase (Cu,ZnSOD) is the antioxidant enzyme that catalyzes the dismutation of superoxide (O2*-) to O2 and H2O2. In addition, Cu,ZnSOD also exhibits peroxidase activity in the presence of H2O2, leading to self-inactivation and formation of a potent enzyme-bound oxidant. We report in this study that lipid peroxidation of L-alpha-lecithin liposomes was enhanced greatly during the SOD/H2O2 reaction in the presence of nitrite anion (NO2-) with or without the metal ion chelator, diethylenetriaminepentacetic acid. The presence of NO2- also greatly enhanced alpha-tocopherol (alpha-TH) oxidation by SOD/H2O2 in saturated 1, 2-dilauroyl-sn-glycero-3-phosphatidylcholine liposomes. The major product identified by HPLC and UV-studies was alpha-tocopheryl quinone. When 1,2-diauroyl-sn-glycero-3-phosphatidylcholine liposomes containing gamma-tocopherol (gamma-TH) were incubated with SOD/H2O2/NO2-, the major product identified was 5-NO2-gamma-TH. Nitrone spin traps significantly inhibited the formation of alpha-tocopheryl quinone and 5-NO2-gamma-TH. NO2- inhibited H2O2-dependent inactivation of SOD. A proposed mechanism of this protection involves the oxidation of NO2- by an SOD-bound oxidant to the nitrogen dioxide radical (*NO2). In this study, we have shown a new mechanism of nitration catalyzed by the peroxidase activity of SOD. We conclude that NO2- is a suitable probe for investigating the peroxidase activity of familial Amyotrophic Lateral Sclerosis-linked SOD mutants.
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PMID:Nitration of gamma-tocopherol and oxidation of alpha-tocopherol by copper-zinc superoxide dismutase/H2O2/NO2-: role of nitrogen dioxide free radical. 978 14

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Previous studies by this laboratory have shown that exposure to workplace ETS results in increased oxidative stress and damage, as measured by increased levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. 8-Hydroxy-2-deoxyguanosine, a marker of oxidative DNA damage, was also 63% greater in the exposed group compared with controls. Subjects in the previous study who reported workplace exposure to ETS were given a 60-day supply of an over-the-counter antioxidant formulation consisting of 3000 microg of beta-carotene, 60 mg of vitamin C, 30 I.U. of alpha-tocopherol, 40 mg of zinc, 40 microg of selenium, and 2 mg of copper. After the 60-day supplementation period, blood samples were again drawn, and the results were compared with the presupplementation values. A 62% decrease in 8-hydroxy-2-deoxyguanosine was observed after supplementation. Lipid peroxidation levels were also decreased, as were the antioxidant enzyme activities. The biochemical evidence suggests that exposure to ETS in the workplace increases oxidative stress and that antioxidant supplementation may provide some protection.
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PMID:Oxidative stress induced by environmental tobacco smoke in the workplace is mitigated by antioxidant supplementation. 982 5


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