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)

The distribution of cells containing copper-zinc superoxide dismutase (CuZn SOD) protein and mRNA was studied in hippocampi from normal humans and patients with Alzheimer's disease (AD) by using immunohistochemistry and in situ hybridization. Using antisera against native and denatured CuZn SOD protein, we have determined that immunostaining was intense in pyramidal neurons of the cornu ammonis, in granule cells of the dentate gyrus and very weak in other cells. In the hippocampus of an Alzheimer's patient, successive immunostaining of the same tissue section by antiCuZn SOD and antipaired helical filaments antisera show that both normal and degenerating cells were labeled by the antiCuZn SOD antiserum. Thus, large pyramidal neurons which are susceptible to degenerative processes in AD have the property to contain high amount of CuZn SOD protein. In situ hybridization was performed on paraformaldehyde-fixed hippocampus sections of normal human brains and AD brains with a 35 S labeled DNA probe homologous to human CuZn SOD mRNA. Our results show that CuZn SOD transcripts are present at high abundance in pyramidal neurons of the CA1-CA4 fields, subiculum, and in granule cells of the dentate gyrus. This cellular distribution is similar to that obtained with the antiCuZn SOD antiserum. This might indicate that biochemical pathways leading to superoxide radicals generation are specially active in these neurons, requiring an active transcription of CuZn-SOD gene.
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PMID:Neuronal localization of copper-zinc superoxide dismutase protein and mRNA within the human hippocampus from control and Alzheimer's disease brains. 206 Aug 34

A sensitive sandwich-type enzyme immunoassay for measurement of human Mn superoxide dismutase (Mn SOD) was developed using purified antibodies specific to Mn SOD. The antisera were raised in rabbits by injecting Mn SOD purified from human liver. The antibody IgG, purified by the use of Mn SOD-coupled Sepharose, showed a single band on the immunoblotting test with a crude liver extract. The assay system consisted of polystyrene balls with immobilized monospecific antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from Escherichia coli. The assay was highly sensitive and the minimum detection limit was 1 pg human Mn SOD/assay tube. Serum Mn SOD concentrations of healthy adults (77.5 +/- 18.0 ng/ml (1 SD), n = 120, 16-64 yr old) were not related to age or sex. Immunoreactive Mn SOD was detectable in most tissues examined except for erythrocytes. The concentrations of immunoreactive Mn SOD and Cu/Zn SOD in the cerebral cortex were not different among the patients with Alzheimer's disease, and the age matched and young patients without neurological disorders.
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PMID:Sensitive enzyme immunoassay for human Mn superoxide dismutase. 228 14

The cellular localization of copper-zinc superoxide dismutase (CuZn SOD) mRNA was determined in the human hippocampus by in situ hybridization with a 35S-labelled DNA probe complementary to human CuZn SOD mRNA. A positive hybridization signal was detected in pyramidal cell layers CA1-CA4 of Ammon's horn (CA), pyramidal cells of subiculum and in the granule cells of the dentate gyrus. The fact that CuZn SOD gene expression is important in neurones which are preferentially vulnerable in neurodegenerative processes such as Alzheimer's disease, suggests a role played by oxygen free radicals in the mechanism of nerve cell death.
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PMID:Localization of copper-zinc superoxide dismutase mRNA in human hippocampus by in situ hybridization. 248 84

CuZn superoxide dismutase and Mn superoxide dismutase were analysed in hypothalamus, nucleus caudatus, hippocampus and cortex gyrus cinguli from 14 patients with dementia of Alzheimer type and from 16 controls. Ample amounts of both enzymes were demonstrated in the brains and there was little difference between the various parts of the brain. There were only small differences in the enzymic activities between the two groups indicating that deficiencies of these enzymes are not a very likely cause of brain degeneration in dementias of Alzheimer type.
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PMID:Superoxide dismutase isoenzymes in normal brains and in brains from patients with dementia of Alzheimer type. 398 75

Cu, Zn superoxide dismutase (SOD) levels in the serum, cerebrospinal fluid (CSF) and skin fibroblasts of patients with dementia of the Alzheimer type (DAT) were estimated using enzyme immunoassay. The SOD mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the age-matched control groups of neurological patients without dementia, the AD group consisting of patients with DAT at ages under 65 years of age as well as the SDAT group of patients with DAT at ages over 65 years of age showed no significant changes in serum or CSF SOD levels. However, the skin fibroblast SOD- and SOD mRNA levels, which were correlate each other, were significantly higher in the AD group (p < 0.05), while lower in the SDAT group (p < 0.05). These results suggest that the determination of the SOD level of skin fibroblast may be useful for diagnosis of DAT and that the abnormality of SOD may play an important role in developing DAT.
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PMID:Cu, Zn superoxide dismutase in patients with dementia of the Alzheimer type. 779 29

Oxidants are ubiquitous in our aerobic environment and could play an etiological role in aging and neurodegenerative diseases such as Alzheimer's disease. All cells contain several antioxidant enzymes, most importantly, superoxide dismutases (MnSOD and CuZnSOD), glutathione peroxidase (GSH-Px), glutathione reductase and catalase. The individual contribution of these antioxidant enzymes in neuronal protection during aging and under in vivo conditions remains unknown. We feel that the use of genetic manipulations to construct cells and/or transgenic mice that specifically overexpress or lack a single function represent a way to an understanding of the role of the individual antioxidant enzymes in neuronal aging. Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all tissues of Down syndrome (DS) patients. It has been suggested that this increment, by accelerating hydrogen peroxide formation, might promote oxidative damage within DS cells and might be involved in the various neurobiological abnormalities found in DS such as premature aging and Alzheimer-type neurological lesions. Moreover, the level of CuZnSOD protein and mRNA is particularly high in pyramidal hippocampal neurons susceptible to degenerative processes in Alzheimer's disease, and in dopaminergic melanized-neurons vulnerable in Parkinson's disease. In order to test this hypothesis, we have created transfected cells and transgenic mice which express human CuZnSOD gene. An oversupply of this enzyme is not beneficial to the brain of transgenic mice and causes increased thiobarbituric-reactive substances (TBARS), an index of lipid peroxidation, and may be due to peroxides generated by an imbalance between enzymatic activities of CuZnSOD and GSH-Px. Unlike what has been observed in transfected cells with the human CuZnSOD gene, but similar to what was found in the DS fetal brain, the GSH-Px activity was not increased in the brain of transgenic mice. One possibility to explain this discrepancy could be the differential cellular localization of these two enzymes in the brain (CuZnSOD in neurons and GSH-Px in glial cells). This heterogeneous cellular distribution of the enzymes implicated in oxygen-free radicals detoxification could participate to a selective neuronal degeneration. Interestingly, overexpression of CuZnSOD in the brain of transgenic mice is associated with an increased MnSOD activity, the mitochondrial form of the enzyme. This increased MnSOD might be a defense response to protect mitochondria from oxidative damage.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Transgenic mice overexpressing copper-zinc superoxide dismutase: a model for the study of radical mechanisms and aging]. 801 10

In this case/control study, serum levels of oxidative stress related parameters such as Fe-binding lactoferrin (LTF), Mn- and Zn,Cu-superoxide dismutase (SOD) were determined by enzyme linked immunoassays in patients suffering from the Alzheimer's dementia as well as in non-demented controls. The Mn-SOD concentration was significantly (P<0.05, U-test) reduced in patients suffering from Alzheimer's disease if compared to non-demented controls. The other parameters investigated did not differ significantly between both groups. Our findings give evidence for the hypothesis of a disturbed free radical metabolism in Alzheimer's disease. The specificity of these results remains to be clarified. Further studies are needed to elucidate the relevance of oxidative stress in the etiopathogenesis of the Alzheimer's disease.
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PMID:Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease. 899 27

Apoptotic, rather than necrotic, nerve cell death now appears as likely to underlie a number of common neurological conditions including stroke, Alzheimer's disease, Parkinson's disease, hereditary retinal dystrophies and Amyotrophic Lateral Sclerosis. Apoptotic neuronal death is a delayed, multistep process and therefore offers a therapeutic opportunity if one or more of these steps can be interrupted or reversed. Research is beginning to show how specific macromolecules play a role in determining the apoptotic death process. We are particularly interested in the critical nature of gradual mitochondrial failure in the apoptotic process and propose that a maintenance of mitochondrial function through the pharmacological modulation of gene expression offers an opportunity for the effective treatment of some types of neurological dysfunction. Our research into the development of small diffusible molecules that reduce apoptosis has grown from studies of the irreversible MAO-B inhibitor (-)-deprenyl. (-)-Deprenyl can reduce neuronal death independently of MAO-B inhibition even after neurons have sustained seemingly lethal damage. (-)-Deprenyl can also influence the process outgrowth of some glial and neuronal populations and can reduce the concentrations of oxidative radicals in damaged cells at concentrations too small to inhibit MAO. In accord with earlier work of others, we showed that (-)-deprenyl alters the expression of a number of mRNAs or of proteins in nerve and glial cells and that the alterations in gene expression/protein synthesis are the result of a selective action on transcription. The alterations in gene expression/protein synthesis are accompanied by a decrease in DNA fragmentation characteristic of apoptosis and the death of responsive cells. The onco-proteins Bcl-2 and Bax and the scavenger proteins Cu/Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD-2) are among the 40-50 proteins whose synthesis is altered by (-)-deprenyl. Since mitochondrial membrane potential correlates with mitochondrial ATP production, we have used confocal laser imaging techniques in living cells to show that the transcriptional changes induced by (-)-deprenyl result in a maintenance of mitochondrial membrane potential, a decrease in intramitochondrial calcium and a decrease in cytoplasmic oxidative radical levels. We therefore propose that (-)-deprenyl acts on gene expression to maintain mitochondrial function and decrease cytoplasmic oxidative radical levels and thereby reduces apoptosis. An understanding of the molecular steps by which (-)-deprenyl selectively alters transcription may lead to the development of new therapies for neurodegenerative diseases.
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PMID:Apoptosis in neurodegenerative disorders: potential for therapy by modifying gene transcription. 926 33

Alzheimer's disease (AD) has been hypothesized to be associated with oxidative stress. In this study, the expression of key oxidative stress-handling genes was studied in hippocampus, inferior parietal lobule, and cerebellum of 10 AD subjects and 10 control subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The content of Mn-, Cu,Zn-superoxide dismutases (Mn- and Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) mRNAs, and the "marker genes" (beta-actin and cyclophilin) mRNAs was determined. This study suggests that gene responses to oxidative stress can be significantly modulated by the general decrease of transcription in the AD brain. To determine if the particular oxidative stress handling gene transcription was induced or suppressed in AD, the "oxidative stress-handling gene/beta-actin" ratios were quantified and compared with control values in all brain regions studied. The Mn-SOD mRNA/beta-actin mRNA ratio was unchanged in all regions of the AD brain studied, but an increase of the Cu,Zn-SOD mRNA/beta-actin mRNA ratio was observed in the AD inferior parietal lobule. The levels of peroxidation handling (CAT, GSHPx, and GSSG-R) mRNAs normalized to beta-actin mRNA level were elevated in hippocampus and inferior parietal lobule, but not in cerebellum of AD patients, which may reflect the protective gene response to the increased peroxidation in the brain regions showing severe AD pathology. The results of this study suggest that region-specific differences of the magnitude of ROS-mediated injury rather than primary deficits of oxidative stress handling gene transcription are likely to contribute to the variable intensity of neurodegeneration in different areas of AD brain.
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PMID:The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease. 1009 42

The mechanism whereby mutations in the presenilin-1 (PS-1) gene on chromosome 14 cause early-onset inherited Alzheimer's disease are unknown. We report that PC6 neural cells (a subclone of PC12 cells) expressing PS-1 mutations (M146V and L286V) exhibit increased superoxide production, nitrotyrosine accumulation, and membrane lipid peroxidation following exposure to amyloid beta-peptide 1-42 (Abeta). Mitochondrial calcium accumulation and membrane depolarization following exposure to Abeta were enhanced in cells expressing mutant PS-1. Overexpression of mitochondrial Mn-SOD greatly reduced superoxide production, nitrotyrosine formation, membrane lipid peroxidation, intramitochondrial calcium accumulation, and membrane depolarization following exposure to Abeta and conferred resistance to the apoptosis-enhancing action of the PS-1 mutations. Nitric oxide synthase inhibitors and the peroxynitrite scavenger uric acid blocked the apoptosis-enhancing action of PS-1 mutations. The data suggest pivotal roles for superoxide production and resulting peroxynitrite formation in the pathogenic mechanism of PS-1 mutations.
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PMID:Superoxide mediates the cell-death-enhancing action of presenilin-1 mutations. 1036 13


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