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)

The excess of genetic information in patients with Down's syndrome (DS) produces an increase in the catalytic activity of superoxide dismutase (SOD1), an antioxidant enzyme coded on chromosome 21. It has been suggested that an increase in oxidative stress in DS patients may cause adverse effects in the cell membranes through the oxidation of polyunsaturated fatty acids (PUFAs). The aim of this study was to evaluate the cellular antioxidant system by determining the catalytic activity of the SOD1, glutathione peroxidase (GPx), catalase (CAT), and glutathione reductase (GR) enzymes and the concentrations of alpha-tocopherol in red blood cells (RBCs) in a group of 72 DS patients. The profile of fatty acids in the phospholipids of RBC membranes was also evaluated. The activity of the erythrocyte antioxidant enzymes is significantly higher in the DS group than in the control group (SOD1, 635 +/- 70 U/g Hb vs 476 +/- 67 U/g Hb; CAT, 1843 +/- 250 U/g Hb vs 1482 +/- 250 U/g Hb; GPx, 23.2 +/- 5.3 U/g Hb vs 21.5 +/- 3.6 U/g Hb; and GR, 9.32 +/- 1.4 U/g Hb vs 6.9 +/- 1.3 U/g Hb, respectively). No differences were observed in RBC alpha-tocopherol concentrations between the two groups studied. Long-chain n6 PUFA (C20:3n6, C20:4n6) concentrations were increased in DS patients, suggesting enhanced delta-6-desaturase activity. The long-chain n3 PUFA (docosahexenoic acid) does not appear to be affected by increased oxidative stress, probably because of the existence of compensatory antioxidant mechanisms.
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PMID:Antioxidant enzymes and fatty acid status in erythrocytes of Down's syndrome patients. 959 Mar 63

The cytoplasmic copper-zinc superoxide dismutase (Cu, Zn SOD; SOD-1) is an abundant and well-conserved intracellular antioxidant enzyme which has been implicated in a number of oxidative stress mediated phenomena, especially Down Syndrome, in which SOD-1 activity is increased due to triplication of chromosome 21 containing the gene and, in hereditary amyotrophic lateral sclerosis, in which the gene is mutated. Overexpression of SOD-1 could theoretically, therefore, lead to increased vulnerability to oxidative stress in two distinct manners: increasing steady-state hydrogen peroxide levels or increasing toxic side reactions. We used two mouse neuronal culture systems--one in which the murine chromosome containing SOD-1 is triplicated and one in which human SOD-1 is a transgene--to test the effect of overexpression of this enzyme on antioxidant status in general and specifically on glutamate mediated oxidative stress. We found that SOD-1 overexpression increases antioxidant status at the same time it decreases vulnerability to glutamate.
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PMID:Effects of overexpression of the cytoplasmic copper-zinc superoxide dismutase on the survival of neurons in vitro. 963 90

The syncytiotrophoblast is the major component of the human placenta, involved in feto-maternal exchanges and secretion of pregnancy-specific hormones. Multinucleated syncytiotrophoblast arises from fusion of mononuclear cytotrophoblast cells. In trisomy 21-affected placentas, we recently have shown that there is a defect in syncytiotrophoblast formation and a decrease in the production of pregnancy-specific hormones. Due to the role of oxygen free radicals in trophoblast cell differentiation, we investigated the role of the key antioxidant enzyme, copper/zinc superoxide dismutase, encoded by chromosome 21 in in vitro trophoblast differentiation. We first observed that overexpression of superoxide dismutase in normal cytotrophoblasts impaired syncytiotrophoblast formation. This was associated with a significant decrease in mRNA transcript levels and secretion of hCG and other hormonal markers of syncytiotrophoblast. We confirmed abnormal cell fusion by overexpression of green fluorescence protein-tagged superoxide dismutase in cytotrophoblasts. In addition, a significant decrease in syncytin transcript levels was observed in superoxide dismutase-transfected cells. We then examined superoxide dismutase expression and activity in isolated trophoblast cells from trisomy 21-affected placentas. Superoxide dismutase mRNA expression (P < 0.05), protein levels (P < 0.01), and activity (P < 0.05) were significantly higher in trophoblast cells isolated from trisomy 21-affected placentas than in those from normal placentas. These results suggest that superoxide dismutase overexpression may directly impair trophoblast cell differentiation and fusion, and superoxide dismutase overexpression in Down's syndrome may be responsible at least in part for the failure of syncytiotrophoblast formation observed in trisomy 21-affected placentas.
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PMID:Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation. 1145 13

One of the most important antioxidant enzymes is superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals to peroxide. The gene for CuZnSOD lies in humans on chromosome 21, and its activity is increased in patients with Down syndrome. However, instead of being beneficial, increased lipid peroxidation is associated with this increased expression, and also studies on bacteria and transgenic animals show that high levels of SOD actually lead to increased lipid peroxidation and hypersensitivity to oxidative stress. Using mathematical models, we investigated the question of how overexpression of SOD can lead to increased oxidative stress, although it is an antioxidant enzyme. We considered several possibilities that have been proposed in the literature, such as CuZnSOD-catalyzed hydroxyl radical formation, superoxide-mediated inhibition of membrane peroxidation, and short-circuiting of the Cu(I)ZnSOD/Cu(II)ZnSOD redox cycle. We found that one of the proposed mechanisms under certain circumstances is able to explain the increased oxidative stress caused by SOD. Furthermore, we identified an additional mechanism that agrees well with experimental observations. We call it the "alternative pathway" mechanism, because it depends on superoxide radicals having alternative pathways besides their reaction with SOD. The alternative pathway mechanism is a very general explanation for SOD-associated oxidative stress, because it does not depend on the specific type of SOD, nor on the redox status of the cell. We therefore think that it might be the common mechanism for the detrimental effects seen in cells and organisms with increased levels of the different forms of superoxide dismutase.
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PMID:Alternative pathways might mediate toxicity of high concentrations of superoxide dismutase. 1524 47