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)

We used light microscopic immunohistochemistry to locate manganese superoxide dismutase, copper zinc superoxide dismutase, catalase, and glutathione-S-transferases in demineralized femora from rats of 4-14 weeks of age. Immunoblots confirmed the specificity of the polyclonal antibodies for the rat proteins of interest. Each of the enzymes exhibited a unique staining pattern. Copper-zinc superoxide dismutase was detected within some articular and epiphyseal chondrocytes of younger animals. Manganese superoxide dismutase was detected within some articular and epiphyseal chondrocytes, within some osteoprogenitor cells and osteoblasts, within many osteoclasts, and within some vascular smooth muscle cells. Catalase was identified within articular chondrocytes, epiphyseal chondrocytes, and osteocytes, whereas staining at the periphery of hypertrophic chondrocytes suggested extracellular and/or cell membrane-associted catalase. Glutathione-S-transferases were detected within and at the periphery of epiphyseal and articular chondrocytes and less prominently within cortical osteocytes. There were no major age-related changes in antioxidant enzyme distribution.
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PMID:Immunohistochemical identification of superoxide dismutases, catalase, and glutathione-S-transferases in rat femora. 157 Jul 63

Manganese superoxide dismutase (MnSOD) levels were monitored as a function of time in culture to determine whether these levels were altered at logarithmic growth versus when the cells exhibited density limitation of growth. For comparison, activities of the antioxidant enzymes copper, zinc superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase were also evaluated. Four cell lines were studied, two of which exhibited density limitation of growth and two of which did not. Each cell line showed a unique antioxidant enzyme profile. The two cell lines that showed density limitation of growth also demonstrated induction of MnSOD at the time when the cells stopped proliferating in culture, whereas the other two cell lines did not show induction of MnSOD. There was no strict correlation between density limitation of growth and activities of the other antioxidant enzymes. To determine whether SOD varied with various phases of the cell cycle, NIH/3T3 cells were synchronized using serum starvation, and then SOD activities were measured during quiescence (G0) and the phase of DNA synthesis (S-phase). MnSOD was decreased during S-phase compared with G0, whereas CuZnSOD was increased during S-phase compared with G0, demonstrating alteration of SOD activities with varying phases of the cell cycle. This study suggests the possibility that increased MnSOD may correlate with decreased cell proliferation and suggests significant alterations in SOD activities during the cell cycle.
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PMID:Antioxidant enzyme levels as a function of growth state in cell culture. 763 59

Immunoperoxidase and immunogold techniques were used to localize the following antioxidant enzyme systems in the adult hamster kidney at the light and ultrastructural levels: superoxide dismutases, catalases, peroxidases and glutathione S-transferases. Each cell type in the kidney showed specific patterns of labelling of these enzymes. For example, proximal and distal tubular and transitional epithelial cells showed significant staining for all of these enzymes, while glomerular cells and cells of the thin loop of Henle did not show significant staining at the light microscope level. In addition, high levels of glutathione peroxidase were found in smooth muscle cells of renal arteries. At the ultrastructural level, each enzyme was found in a specific subcellular location. Manganese superoxide dismutase was found in mitochondria, catalase was localized in peroxisomes, while copper, zinc superoxide dismutase and glutathione S-transferase (liver and placental forms) were found in both the nucleus and cytoplasm. Glutathione peroxidase was found to have a broad intracellular distribution, with localization in mitochondria, peroxisomes, nucleus, and cytoplasm. Microvilli of tubular cells were labelled by antibodies to catalase, copper, zinc superoxide dismutase, glutathione peroxidase, and glutathione S-transferases. Cell types that were negative by light microscopy immunoperoxidase studies showed definite labelling with immunogold post-embedding ultrastructural techniques (glomerular cells and cells of the loop of Henle), demonstrating the greater sensitivity of the latter technique. These observations demonstrate that there are large variations in the levels of antioxidant enzymes in different cell types, and that even within a distinct cell type, the levels of these enzymes vary in different subcellular locations. Our results demonstrate for the first time the overall antioxidant enzyme status of individual kidney cell types, thereby explaining why different cell types have differing susceptibilities to oxidant stress. Possible physiological and pathological consequences of these findings are discussed.
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PMID:Immunolocalization of antioxidant enzymes in adult hamster kidney. 784 85

Reactive oxygen species of mitochondrial origin have been implicated in regulating the expression of several tumor necrosis factor (TNF)-induced genes. Manganese superoxide dismutase (Mn-SOD) is one of many genes, but only antioxidant enzyme, induced in response to tumor necrosis factor. Mn-SOD is a nuclear-encoded mitochondrial matrix protein and serves a protective function by detoxifying superoxide. To address the role of superoxide in regulating gene expression in response to TNF, we have constitutively overexpressed Mn-SOD in a human fibrosarcoma cell line and asked what effect this has on the expression of a number of TNF-responsive genes using reverse transcription-polymerase chain reaction. Of the TNF-induced transcripts analyzed, only interleukin-1alpha (IL-1alpha) was modulated in response to Mn-SOD overexpression. In all cases of Mn-SOD overexpression, IL-1alpha protein and mRNA levels were lowered constitutively and in response to TNF when compared to the parental and mock-transfected cell lines. The induction of IL-1alpha by TNF can also be decreased by growth in 3% oxygen as compared to growth in 21% O2; in addition, growth in low oxygen lowers the basal level of IL-1alpha protein. The effect of Mn-SOD overexpression on IL-1alpha expression can be overcome by treatment with the protein kinase C activator, phorbol 12-myristate 13-acetate. Mn-SOD overexpression and low oxygen alter IL-1alpha mRNA levels by decreasing the stability of the IL-1alpha mRNA. These findings indicate that both Mn-SOD and O2 may regulate the levels of a cellular oxidant involved in both basal and TNF-induced IL-1alpha expression, presumably superoxide.
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PMID:Manganese superoxide dismutase modulates interleukin-1alpha levels in HT-1080 fibrosarcoma cells. 870 51

Manganese superoxide dismutase (MnSOD) is a primary antioxidant enzyme critical for maintaining normal cell function and for survival. Previously, we cloned the entire MnSOD gene, including a 0.782-kb 5' DNA sequence, from a human embryonic lung fibroblast cell line. Sequence analysis indicates that the promoter of the human MnSOD gene is TATA-less and CAAT-less, and the DNA sequence immediately upstream from the transcription start site is GC rich. To study the function and regulation of the human MnSOD promoter, we cloned a 257-bp sequence (P7) containing the transcription start site and the 5' GC-rich region. Consensus analysis and DNase I footprinting assay indicated that P7 contains multiple Sp1- and AP-2-binding sites. Deletions of the P7 sequence diminished the promoter activity and decreased the response to Sp1 protein. The first three Sp1 consensus sites were required for high promoter activity in mammalian cells and enhanced promoter activity in Drosophila Schneider Line 2 (SL2) cells. In the SL2 cells, Sp1 activated the P7 activity in a dose-dependent manner. In contrast, cotransfections with AP-2 expression vector marginally increased P7 activities in human hepatocarcinoma HepG2 cells. The results suggest that Sp1 is an important regulator for the transcriptional activities of P7, whereas AP-2 is a minor activator for P7 and competes with Sp1 for binding sites which may downregulate P7 function.
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PMID:Transcriptional regulation of the 5' proximal promoter of the human manganese superoxide dismutase gene. 983 1

There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity.
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PMID:Manganese superoxide dismutase overexpression attenuates MPTP toxicity. 984 95

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that reduces superoxide anion to hydrogen peroxide in cell mitochondria. MnSOD is overexpressed in normal aging brain and in various central nervous system disorders; however, the mechanisms mediating the upregulation of MnSOD under these conditions remain poorly understood. We previously reported that cysteamine (CSH) and other pro-oxidants rapidly induce the heme oxygenase-1 (HO-1) gene in cultured rat astroglia followed by late upregulation of MnSOD in these cells. In the present study, we demonstrate that antecedent upregulation of HO-1 is necessary and sufficient for subsequent induction of the MnSOD gene in neonatal rat astroglia challenged with CSH or dopamine, and in astroglial cultures transiently transfected with full-length human HO-1 cDNA. Treatment with potent antioxidants attenuates MnSOD expression in HO-1-transfected astroglia, strongly suggesting that intracellular oxidative stress signals MnSOD gene induction in these cells. Activation of this HO-1-MnSOD axis may play an important role in the pathogenesis of Alzheimer disease, Parkinson disease and other free radical-related neurodegenerative disorders. In these conditions, compensatory upregulation of MnSOD may protect mitochondria from oxidative damage accruing from heme-derived free iron and carbon monoxide liberated by the activity of HO-1.
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PMID:Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene expression in oxidatively-challenged astroglia. 1094 21

Manganese superoxide dismutase (Mn-SOD), a critical mitochondrial antioxidant enzyme, becomes inactivated and nitrated in vitro and potentially in vivo by peroxynitrite. Since peroxynitrite readily reacts with transition metal centers, we assessed the role of the manganese ion in the reaction between peroxynitrite and Mn-SOD. Peroxynitrite reacts with human recombinant and Escherichia coli Mn-SOD with a second order rate constant of 1.0 +/- 0.2 x 10(5) and 1.4 +/- 0.2 x 10(5) m(-)1 s(-)1 at pH 7.47 and 37 degrees C, respectively. The E. coli apoenzyme, obtained by removing the manganese ion from the active site, presents a rate constant <10(4) m(-)1 s(-)1 for the reaction with peroxynitrite, whereas that of the manganese-reconstituted apoenzyme (apo/Mn) was comparable to that of the holoenzyme. Peroxynitrite-dependent nitration of 4-hydroxyphenylacetic acid was increased 21% by Mn-SOD. The apo/Mn also promoted nitration, but the apo and the zinc-substituted apoenzyme (apo/Zn) enzymes did not. The extent of tyrosine nitration in the enzyme was also affected by the presence and nature (i.e. manganese or zinc) of the metal center in the active site. For comparative purposes, we also studied the reaction of peroxynitrite with low molecular weight complexes of manganese and zinc with tetrakis-(4-benzoic acid) porphyrin (tbap). Mn(tbap) reacts with peroxynitrite with a rate constant of 6.8 +/- 0.1 x 10(4) m(-)1 s(-)1 and maximally increases nitration yields by 350%. Zn(tbap), on the other hand, affords protection against nitration. Our results indicate that the manganese ion in Mn-SOD plays an important role in the decomposition kinetics of peroxynitrite and in peroxynitrite-dependent nitration of self and remote tyrosine residues.
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PMID:Reaction of peroxynitrite with Mn-superoxide dismutase. Role of the metal center in decomposition kinetics and nitration. 1115 62

Manganese superoxide dismutase (MnSOD), an inductive antioxidant enzyme, can protect cells from oxidative injury to the mitochondria. The elevation of MnSOD activity in cells can effectively prevent many diseases associated with oxidative stress. Polysaccharide Krestin (PSK), a kind of protein-bound polysaccharide extracted from Coriolus versicolor, is used as an immune response modifier in anti-tumor therapy. We have previously found that PSK could alleviate the oxidative injury that oxidized low density lipoprotein (Ox-LDL) brought to monocytes/macrophages, and therefore had some preventive or therapeutic effect on atherosclerosis. In order to find out if the effects of PSK were associated with the alteration ofantioxidant enzymes, we investigated its effect on MnSOD activity and gene expression in mouse peritoneal macrophages. The results showed that PSK could enhance SOD activity and increase the contents ofMnSOD mRNA in mouse peritoneal macrophages. Furthermore, the induction of MnSOD by PSK could be blocked by cycloheximide and actinomycin D.
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PMID:Polysaccharide Krestin enhances manganese superoxide dismutase activity and mRNA expression in mouse peritoneal macrophages. 1115 46

Manganese superoxide dismutase (Mn-SOD) is a primary antioxidant enzyme whose expression is essential for life in oxygen. Mn-SOD has tumor suppressor activity in a wide variety of tumors and transformed cell systems. Our initial observations revealed that Mn-SOD expression was inversely correlated with expression of AP-2 transcription factors in normal human fibroblasts and their SV-40 transformed counterparts. Thus we hypothesized that AP-2 may down-regulate Mn-SOD expression. To examine the functional role of AP-2 on Mn-SOD promoter transactivation we cotransfected AP-2-deficient HepG2 cells with a human Mn-SOD promoter-reporter construct and expression vectors encoding each of the three known AP-2 family members. Our results indicated that AP-2 could significantly repress Mn-SOD promoter activity, and that this repression was both Mn-SOD promoter and AP-2-specific. The three AP-2 proteins appeared to play distinct roles in Mn-SOD gene regulation. Moreover, although all three AP-2 proteins could repress the Mn-SOD promoter, AP-2alpha and AP-2gamma were more active in this regard than AP-2beta. Transcriptional repression by AP-2 was not a general effect in this system, because another AP-2-responsive gene, c-erbB-3, was transactivated by AP-2. Repression of Mn-SOD by AP-2 was dependent on DNA binding, and expression of AP-2B, a dominant negative incapable of DNA binding, relieved the repression on Mn-SOD promoter and reactivated Mn-SOD expression in the AP-2 abundant SV40-transformed fibroblast cell line MRC-5VA. These results indicate that AP-2-mediated transcriptional repression contributes to the constitutively low expression of Mn-SOD in SV40-transformed fibroblasts and suggest a mechanism for Mn-SOD down-regulation in cancer.
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PMID:A family of AP-2 proteins down-regulate manganese superoxide dismutase expression. 1127 50


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