Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide dismutase (SOD) is an essential enzyme protecting cells against oxidative stress. However, its specific role under different conditions is not clear. To study the possible role of SOD in the cell during respiration, Saccharomyces cerevisiae single and double mutants with inactivated SOD1 and/or SOD2 genes growing on ethanol as an energy and carbon source were used. Activities of antioxidant and associated enzymes as well as the level of protein carbonyls were measured. SOD activity was significantly higher in a Mn-SOD deficient strain than that in the wild-type parental strain, but significantly lower in a Cu, Zn-SOD mutant. A strong positive correlation between SOD and catalase activities (R(2) = 0.99) shows possible protection of catalase by SOD from inactivation in vivo and/or decrease in catalase activity because of lower H(2)O(2) formation in the mutant cells. SOD deficiency resulted in a malate dehydrogenase activity increase, whereas glucose-6-phosphate dehydrogenase (G6PDH) activity was lower in SOD-deficient strains. Linear and non-linear positive correlations between SOD and isocitrate dehydrogenase activities are discussed. No changes in the activity of glutathione reductase and protein carbonyl levels support the idea that SOD-deficient cells are not exposed to strong oxidative stress during exponential growth of yeast cultures on ethanol.
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PMID:Growth on ethanol results in co-ordinated Saccharomyces cerevisiae response to inactivation of genes encoding superoxide dismutases. 1770 88

The aim of the study was to investigate relationship between activity of superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNFalpha) and between Ala-9Val polymorphism in the gene encoding MnSOD (SOD2) and the initial stage and prognosis of the head and neck squamous cell carcinoma (HNSCC). Prospective study cohort comprised 88 patients who underwent surgical treatment for the diagnosis of HNSCC (53 patients were diagnosed with locoregional metastatic spread (N+) at the time of diagnosis). After the initial surgery subjects were followed for the subsequent period of 26 months during which 14 manifested relapse. Genotypes were detected by the PCR-based methodology. Activity of p-SOD, ery-SOD and TNFalpha were determined by ELISA, and the concentration of MDA by high performance liquid chromatography. Genotype and allele frequencies of the Ala-9Val differed neither between groups defined according to the stage of primary disease (TNM), nor between relapse vs. remission groups after the follow-up (p>0.05). Activity of p-SOD was significantly higher in T3/4 stage compared to T1/2 (p=0.01) and was also higher in N+ compared to N0 patients (p=0.002). Carriers of the Ala/Ala genotype had higher p-SOD activity (p=0.04). There was no significant difference in DFI between SOD2 genotype groups (p>0.05), however, the Ala/Ala group exhibited the shortest median DFI. In conclusion, our results suggest that increased p-SOD at the time of the initial treatment for HNSCC is connected with greater extent and nodal metastatic spread of the initial disease and with an earlier relapse of the disease. Progression of the disease might be further modified by the presence of Ala/Ala genotype of the SOD2. Activity of p-SOD could thus offer diagnostic as well as prognostic value.
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PMID:Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases. 1782 22

Manganese superoxide dismutase (MnSOD or SOD2) is a key mitochondrial enzymatic antioxidant. Arguably the most striking phenotype associated with complete loss of SOD2 in flies and mice is shortened life span. To further explore the role of SOD2 in protecting animals from aging and age-associated pathology, we generated a unique collection of Drosophila mutants that progressively reduce SOD2 expression and function. Mitochondrial aconitase activity was substantially reduced in the Sod2 mutants, suggesting that SOD2 normally ensures the functional capacity of mitochondria. Flies with severe reductions in SOD2 expression exhibited accelerated senescence of olfactory behavior as well as precocious neurodegeneration and DNA strand breakage in neurons. Furthermore, life span was progressively shortened and age-dependent mortality was increased in conjunction with reduced SOD2 expression, while initial mortality and developmental viability were unaffected. Interestingly, life span and age-dependent mortality varied exponentially with SOD2 activity, indicating that there might normally be a surplus of this enzyme for protecting animals from premature death. Our data support a model in which disruption of the protective effects of SOD2 on mitochondria manifests as profound changes in behavioral and demographic aging as well as exacerbated age-related pathology in the nervous system.
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PMID:Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging. 1807 70

Mice lacking the 66 kDa isoform of the adapter molecule shcA (p66(shcA)) display increased resistance to oxidative stress and delayed aging. In cultured cell lines, p66 promotes formation of Reactive Oxygen Species (ROS) in mitochondria, and apoptotic cell death in response to a variety of pro-oxidant noxious stimuli. As mitochondrial ROS and oxidative cell damage are clearly involved in alcohol-induced pathology, we hypothesized that p66 may also have a role in ethanol. In vivo, changes observed in p66+/+ mice after 6-week exposure to ethanol in the drinking water, including elevated serum alanine aminotransferase (ALT), liver swelling and evident liver steatosis, were significantly attenuated in p66-/- mutant mice. Biochemical analysis of liver tissues revealed induction of the p66 protein by ethanol, whereas p66-deficient livers responded to alcohol with a significant upregulation of the mitochondrial antioxidant enzyme MnSOD, nearly absent in control mice. Evidence of an inverse correlation between expression level of p66 and protection from alcohol-induced oxidative stress was also confirmed in vitro in primary hepatocytes and in HepG2-E47 cells, an ethanol-responsive hepatoma cell line. In fact, MnSOD upregulation by exposure to ethanol in vitro was much more pronounced in p66KO versus wild-type isolated liver cells, and blunted in HepG2 cells overexpressing p66shc. p66 overexpression also prevented the activation of a luciferase reporter gene controlled by the SOD2 promoter, indicating that p66 repression of MnSOD operates at a transcriptional level. Finally, p66 generated ROS in HepG2 cells and potentiated oxidative stress and mitochondrial depolarization by ethanol. Taken together, the above observations clearly indicate a role for p66 in alcohol-induced cell damage, likely via a cell-autonomous mechanism involving reduced expression of antioxidant defenses and mitochondrial dysfunction.
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PMID:Role of the life span determinant P66(shcA) in ethanol-induced liver damage. 1849 Aug 96

The superoxide dismutases (SODs) are first-line enzymatic antioxidants that dismute superoxide anion (O(2)(-)*) to produce hydrogen peroxide (H(2)O(2)). The primary objective was to characterize, by western blot analysis, the expression of two SODs, the cytosolic (Cu,ZnSOD or SOD1) and the mitochondrial (MnSOD or SOD2) forms in three sections of the oviduct, i.e. isthmus (I), ishtmic-ampullary junction (IA), and ampulla (A), during the estrous cycle. The Cu,ZnSOD and MnSOD proteins were mostly expressed in the ampulla (I<IA<A; P<0.0093). Expression of Cu,ZnSOD was lowest during metestrus (P<0.0041) and it was mostly expressed in the oviduct contralateral to the CL (P=0.0019). The expression of MnSOD was consistent throughout the cycle. Based on immunohistochemistry, the SODs were present in all cell types of the oviduct, with variations among oviductal sections. We inferred that the expression of Cu,ZnSOD was influenced by the hormonal milieu. Furthermore, variations among oviduct sections in protein expression profile of SODs suggested they have an important role in preserving and capacitating sperm.
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PMID:Expression of superoxide dismutases in the bovine oviduct during the estrous cycle. 1857 35

The health effects of low-dose radiation exposure are of public concern. Although molecular events in the cellular response to high-dose-rate radiation exposure have been fully investigated, effects of long-term exposure to extremely low-dose-rate radiation remain unclear. Protein expression was analyzed by two-dimensional electrophoresis in livers from mice irradiated for 485 days (22 hr/day) at low-dose-rates of 0.032 microGy/min, 0.65 microGy/min and 13 microGy/min (total doses of 21 mGy, 420 mGy and 8000 mGy, respectively). One of the proteins that showed marked changes in expression was identified as rhodanese (thiosulfate sulfurtransferase). Rhodanese expression was increased after irradiation at 0.65 microGy/min and 13 microGy/min, while its expression was not changed at 0.032 microGy/min. Rhodanese is a detoxification enzyme, probably related to the regulation of antioxidative function. However, antioxidative proteins, such as superoxide dismutase (SOD)1 (also known as Cu,Zn-SOD) and SOD2 (also known as Mn-SOD), which can be induced by high-dose-rate radiation, were not induced at any low-dose-rates tested. These findings indicate that rhodanese is a novel protein induced by low-dose-rate radiation, and further analysis could provide insight into the effects of extremely low-dose-rate radiation exposure.
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PMID:Induction of rhodanese, a detoxification enzyme, in livers from mice after long-term irradiation with low-dose-rate gamma-rays. 1895 32

Once considered as a mere by-product of respiration, mitochondrial generation of reactive oxygen species (ROS) has recently emerged as a genetically controlled phenomenon, involved in complex intracellular signal transduction cascades that directly regulate cell survival and death in responses to environmental stressors. These cascades are involved in the pathogenesis of several major age-related diseases, such as cancer and neurodegeneration, and also appear to somehow regulate the "normal" ageing process. The present short review summarizes recent discoveries on mitochondrial reactive oxygen species regulation by p53, a tumor suppressor protein and p66shc, a protein implicated in the life-span determination. It also outlines the emerging network whereby these molecules cross-talk with each other and with the mitochondrial antioxidant system, namely MnSOD (SOD2), another life-span determining protein, to regulate oxidative stress in the organelle. This molecular circuit, which comprises two genetic determinants of longevity and a major tumor suppressor gene, also provides a theoretical framework connecting senescence and cancer.
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PMID:The p53-p66shc-Manganese Superoxide Dismutase (MnSOD) network: a mitochondrial intrigue to generate reactive oxygen species. 1899 40

Human epidemiological studies have indicated that low birth weight associated with an adverse intrauterine environment is related to a greater incidence of cardiovascular disorders in later life. In the foetus, endogenous glucocorticoids generally increase if there is intrauterine nutrient deficiency. The consequent glucocorticoid hyperexposure has been hypothesised to cause in utero programming of atherogenic genes. We investigated the effect of oral treatment with the synthetic glucocorticoid dexamethasone during early or late pregnancy in marmoset monkeys on oxidative and antioxidant status in the offspring. Urinary concentrations of F(2)-isoprostanes were quantified as markers for in vivo oxidative stress. Expression of the mRNAs for the antioxidant enzymes cytosolic glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (GPx-4), cytosolic Cu,Zn-superoxide dismutase (SOD1), mitochondrial Mn-superoxide dismutase (SOD2), glutathione reductase (GSR), modifier subunit of glutamate-cysteine ligase (GCLM) and catalase were determined in the aorta. Three groups of pregnant marmosets (10 animals per group) were treated orally for one week with vehicle, or with dexamethasone (5 mg/kg daily) during two gestation windows: early dexamethasone group, pregnancy day 42-48, and late dexamethasone group, pregnancy day 90-96. In one male sibling of each litter (10 males per group), aortas were taken at 2 years of age. In the late dexamethasone group a higher aortic mRNA expression for GPx-1 (p < 0.023), MnSOD (p < 0.016), GCLM (p < 0.019) and GSR (p < 0.014) in comparison to the controls was observed. Aortic expression in the early dexamethasone group was statistically significantly higher only for GSR mRNA (p < 0.038). No significant changes in urinary F(2)-isoprostane concentrations between controls, early and late dexamethasone groups at 2 years of age were observed. Hence, prenatal exposure to dexamethasone in the third trimester leads to increased mRNA expression of several aortic antioxidant enzymes in the offspring. This expression pattern was not temporally related to oxidative stress, and it may reflect in utero re-programming of aortic antioxidant gene expression during prenatal glucocorticoid exposure.
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PMID:Prenatal dexamethasone exposure in the common marmoset monkey enhances gene expression of antioxidant enzymes in the aorta of adult offspring. 1900 75

Autophagy is involved in human diseases and is regulated by reactive oxygen species (ROS) including superoxide (O(2)(*-)) and hydrogen peroxide (H(2)O(2)). However, the relative functions of O(2)(*-) and H(2)O(2) in regulating autophagy are unknown. In this study, autophagy was induced by starvation, mitochondrial electron transport inhibitors, and exogenous H(2)O(2). We found that O(2)(*-) was selectively induced by starvation of glucose, L-glutamine, pyruvate, and serum (GP) whereas starvation of amino acids and serum (AA) induced O(2)(*-) and H(2)O(2). Both types of starvation induced autophagy and autophagy was inhibited by overexpression of SOD2 (manganese superoxide dismutase, Mn-SOD), which reduced O(2)(*-) levels but increased H(2)O(2) levels. Starvation-induced autophagy was also inhibited by the addition of catalase, which reduced both O(2)(*-) and H(2)O(2) levels. Starvation of GP or AA also induced cell death that was increased following treatment with autophagy inhibitors 3-methyladenine, and wortamannin. Mitochondrial electron transport chain (mETC) inhibitors in combination with the SOD inhibitor 2-methoxyestradiol (2-ME) increased O(2)(*-) levels, lowered H(2)O(2) levels, and increased autophagy. In contrast to starvation, cell death induced by mETC inhibitors was increased by 2-ME. Finally, adding exogenous H(2)O(2) induced autophagy and increased intracellular O(2)(*-) but failed to increase intracellular H(2)O(2). Taken together, these findings indicate that O(2)(*-) is the major ROS-regulating autophagy.
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PMID:Superoxide is the major reactive oxygen species regulating autophagy. 1940 26

Superoxide excess plays a central role in tissue damage that results from diabetes, but the mechanisms of superoxide overproduction in diabetic nephropathy (DN) are incompletely understood. In the present study, we investigated the enzyme superoxide dismutase (SOD), a major defender against superoxide, in the kidneys during the development of murine DN. We assessed SOD activity and the expression of SOD isoforms in the kidneys of two diabetic mouse models (C57BL/6-Akita and KK/Ta-Akita) that exhibit comparable levels of hyperglycemia but different susceptibility to DN. We observed down-regulation of cytosolic CuZn-SOD (SOD1) and extracellular CuZn-SOD (SOD3), but not mitochondrial Mn-SOD (SOD2), in the kidney of KK/Ta-Akita mice which exhibit progressive DN. In contrast, we did not detect a change in renal SOD expression in DN-resistant C57BL/6-Akita mice. Consistent with these findings, there was a significant reduction in total SOD activity in the kidney of KK/Ta-Akita mice compared with C57BL/6-Akita mice. Finally, treatment of KK/Ta-Akita mice with a SOD mimetic, tempol, ameliorated the nephropathic changes in KK/Ta-Akita mice without altering the level of hyperglycemia. Collectively, these results indicate that down-regulation of renal SOD1 and SOD3 may play a key role in the pathogenesis of DN.
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PMID:Reduction of renal superoxide dismutase in progressive diabetic nephropathy. 1947 Jun 81


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