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)

Human liver manganese superoxide dismutase has been purified by a short procedure that includes a tri-phase partitioning step to provide materials that can be crystallized from ammonium sulfate. X-ray diffraction studies at 3 A resolution show that the crystals belong to the hexagonal space group P6(1)22 or P6(5)22, with cell dimensions a = b = 81.1 A, c = 242.2 A. Manganese superoxide dismutase levels as determined by enzymatic assay as well as by enzyme-linked immunosorbent assay indicated that considerable variations occur in different livers but the total superoxide dismutase activity (Mn superoxide dismutase plus Cu,Zn superoxide dismutase) seems to be kept at constant values.
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PMID:Preparation of human manganese superoxide dismutase by tri-phase partitioning and preliminary crystallographic data. 202 55

Oxidative damage to the cell has been implicated in the pathogenesis of a number of disorders, including chronic inflammation, aging, and cancer. Manganese superoxide dismutase (Mn-SOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxide radicals and other excited oxygen species. In this report we describe the genomic organization and DNA sequence of the murine MnSOD gene. This gene is interrupted by four introns. The coding sequence of this gene was examined in C57BL/6J and C3H/HeJ mice that are SUSCEPTIBLE AND RESISTANT, respectively, to the pulmonary injuries induced by the inhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the size or steady-state level of this transcript, biologic variability in the pulmonary inflammatory response to ozone and hyperoxia does not arise from an altered gene structure. Examination of the noncoding sequence revealed a dC.dA polymorphism in intron 2 and a StyI RFLV in intron 4 of the MnSOD gene. These sequence and mapping data provide the basis for continued study of biologic variability in the MnSOD gene as a cause of disease.
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PMID:Structure and DNA sequence of the mouse MnSOD gene. 761 35

Manganese superoxide dismutase (Mn-SOD; EC 1.15.1.1) was purified from germinating seeds of Scots pine (Pinus sylvestris L.) 3 days after the start of imbibition. The purification schedule included (NH4)2SO4 fractionation, anion-exchange and hydrophobic-interaction chromatographies and chromatofocusing. Purified Mn-SOD had an apparent specific activity of 4,130 McCord-Fridovich units (mg protein)-1. The molecular mass of the holoenzyme was estimated to be 91 kDa by size-exclusion chromatography, and a molecular mass of 23 kDa was determined by SDS-PAGE. However, isoelectric focusing demonstrated that the purified enzyme consisted of three similarly migrating isoforms, with isoelectric points of approximately 6.5. NH2-terminal amino acid sequencing of purified Mn-SOD revealed no differences among the three isoforms. The comparison of the first 32 NH2-terminal amino acids with sequences of NH2-terminal amino acids of Mn-SODs from angiosperms reflected the phylogenetic distances between Scots pine, which is a gymnosperm, and angiospermic species. Cell fractionation suggested the mitochondrial localization of Mn-SODs and no evidence for glyoxysomal localization was found. Mn-SOD activity was absent from dry seeds. It was detectable at a considerable level after imbibition for 24 h, and it was again absent from 3-week-old seedlings.
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PMID:Isolation and purification of mitochondrial Mn-superoxide dismutase from the gymnosperm Pinus sylvestris L. 798 61

Manganese superoxide dismutase (MnSOD, encoded by the SOD2 gene mapping to chromosome 6q25) has been implicated as a tumor suppressor and as a metastasis suppressor in some tumor cell lines. We showed that introduction of an intact chromosome 6 into the metastatic melanoma cell line C8161 completely suppressed metastasis but did not affect tumorigenicity (Welch et al., (1994) Oncogene 9:255). The purpose of this study was to test whether SOD2 is the gene responsible for metastasis suppression. MnSOD protein levels of C8161 (measured by Western blot), before and after transfer of chromosome 6, showed no correlation with metastatic potential. To determine whether the lack of correlation was due to mutant, nonfunctional SOD2, a highly metastatic subclone of C8161 (C8161c1.9) was transfected with functional SOD2 or vector control (pSFFV). Metastatic potential and tumorigenicity were unchanged. Southern and Northern blots confirmed the presence of the transfected SOD2; however, total MnSOD protein and antioxidant activity were not significantly altered. These results suggest that levels of MnSOD are highly regulated within C8161 melanoma cells and that SOD2 does not suppress tumor formation nor metastatic potential in all human melanomas.
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PMID:SOD2 (MnSOD) does not suppress tumorigenicity or metastasis of human melanoma C8161 cells. 857 3

Lipopolysaccharide (LPS) treatment increases survival of rats, but not of mice, during hyperoxia. Manganese superoxide dismutase (Mn SOD) in the lung plays a critical role in LPS-induced tolerance to hyperoxia in rats. Therefore, we now compared the response of lung Mn SOD with treatment of mice and rats with LPS. LPS treatment of rats increased Mn SOD activity and protein concentration, did not change its specific activity, increased Mn SOD mRNA concentration 35-fold, and elevated Mn SOD synthesis 50% without changing general protein synthesis. LPS treatment of mice did not alter any of these parameters except for a 16-fold increase in Mn SOD mRNA concentration. Mn SOD translational efficiency (synthesis/mRNA concentration) was diminished 93% in rat lung and 76% in mouse lung by treatment with LPS. However, the absolute translational efficiency was twofold higher in lungs of LPS-treated rats than in lungs of LPS-treated mice. The failure of LPS to raise Mn SOD activity in mouse lungs is due, at least in part, to a smaller increase in Mn SOD mRNA and lower translational efficiency in LPS-treated mice than in LPS-treated rats.
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PMID:Regulation of lung manganese superoxide dismutase: species variation in response to lipopolysaccharide. 1033 25

Manganese superoxide dismutase Mn-SOD plays a major role in protecting mitochondria from oxidative damage. Overexpression of Mn-SOD maintains cell survival under conditions that lead to apoptotic death. In addition to the antioxidative enzyme, platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation by activating survival signaling pathways in various cells. Here we show that PDGF induced the expression of the Mn-SOD gene in NIH3T3 cells, and its induction was associated with early growth response-1 (Egr-1), a transcription factor. An electrophoretic mobility shift assay demonstrated that Egr-1 bound to the proximal promoter of the Mn-SOD gene in response to PDGF. The proximal promoter region of Mn-SOD was shown to be transcriptionally responsive to both basal and PDGF stimulation by transfection studies. Forced expression of Egr-1 in the cells activated Mn-SOD transcription in a dose-dependent manner. The pathway by which PDGF induced Egr-1 involved the mitogen-activated protein kinase kinase-1 (MEK1) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), because the effect of PDGF on the induction of Egr-1 was blocked by U0126, a specific MEK1 inhibitor. These findings indicate that the induction of Mn-SOD is part of the anti-apoptotic properties mediated by PDGF.
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PMID:Early growth-responsive-1-dependent manganese superoxide dismutase gene transcription mediated by platelet-derived growth factor. 1151 24

Manganese superoxide dismutase (GP-MnSOD), a component of the so-called 'green protein' (green protein complex) from the facultative anaerobic halodenitrifier Bacillus halodenitrificans, has been crystallized using the hanging-drop vapor diffusion method. Crystals have unit-cell parameters a=b=93.4 A, c=65.0 A, and belong to the space group P4(3)2(1)2. Preliminary analysis indicates there is one monomer in each asymmetric unit. The structural information from this enzyme will enrich our knowledge on its high catalytic activity and its possible role in green protein complex.
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PMID:Crystallization and preliminary crystallographic analysis of manganese superoxide dismutase from Bacillus halodenitrificans. 1205 40

Manganese superoxide dismutase (Mn-SOD, SOD2) is an inducible antioxidant localized to the mitochondria, which have been shown to be both the sites of superoxide anion (O(2)*-)) production and the target of free radical attacks. Knock-out mice with targeted disruption of Sod2 (SOD2-KO) are more susceptible to ischemic damage than their wild-type (WT) counterparts, showing increased loss of mitochondrial cytochrome c after trauma, but less apoptotic cell death in the first 24 h following controlled cortical injury. In this study, we sought to investigate whether oxidative stress plays a significant role in the development of secondary brain damage following cold injury-induced brain trauma (CIBT), a model of vasogenic edema. We first measured the levels of O(2)(*-) production 2 h after CIBT by means of in situ hydroethidine oxidation. We then examined lesion size, brain swelling, apoptosis by morphology and TUNEL-staining, neutrophil infiltration, and hemorrhage rates in both SOD2-KO and WT mice at 1, 3, and 7 days post-CIBT. We found no significant differences between SOD2-KO and WT littermates in any of the paradigms or endpoints studied. There was, however, a significant increase in hemorrhagic transformations in all animals that paralleled a robust inflammatory response at 3 days post insult compared with the 24-h endpoint. In the CIBT model used in this study, a 50% reduction in SOD2 activity did not appear to alter the injury response, suggesting that accumulation of free radicals does not play a significant role in secondary brain damage as previously thought with this particular model.
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PMID:Effects of cold injury-induced trauma in manganese superoxide dismutase-deficient mice. 1290 41

A cDNA encoding a mitochondrial manganese superoxide dismutase (mtMnSOD) was cloned from the hepatopancreas of giant freshwater prawn Macrobrachium rosenbergii using reverse transcription polymerase chain reaction (RT-PCR) by degenerate primers. Both 3'- and 5'-regions were isolated by rapid amplification of cDNA end (RACE) PCR method. Analysis of nucleotide sequence revealed that the mtMnSOD full-length cDNA consists of 1202bp containing an open reading frame of 654bp, which encodes a protein consisting of 218 amino acids including a signal peptide of 16 amino acid residues. The calculated molecular mass of the mature proteins (202 amino acids) is 24kDa with an estimated pI of 7.12. Two putative N-glycosylation sites, NXT and NXS were observed in the mtMnSOD. Manganese superoxide dismutase signatures from 180 to 187 (DVWEHAYY), and four conserved amino acids responsible for binding manganese were observed (H48, H96, D180 and H184). Sequence comparison showed that the mtMnSOD deduced amino acid sequence of Macrobrachium rosenbergii has similarity of 88%, 78%, 56%, 54% and 46% to that of blue crab Callinectes sapidus, crucifix crab Charybdis feriatus, brown shrimp Farfantepenaeus aztecus, European lobster Palinurus vulgaris, and grass shrimp Palaemontes pugio, respectively, and has similarity of 45%, 44%, 43%, 26% and 25% to cytMnSOD (cytosolic MnSOD) deduced amino acid sequence of blue crab C. sapidus, prawn M. rosenbergii, tiger shrimp Penaeus monodon, grass shrimp P. pugio and brown shrimp F. aztecus, respectively. Quantitative real-time RT-PCR analysis showed that levels of mtMn-SOD transcripts in hepatopancreas and haemocytes were not significantly different between the M. rosenbergii injected with Lactococcus garvieae, and that injected with saline after 3h to 24h.
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PMID:Cloning and characterisation of mitochondrial manganese superoxide dismutase (mtMnSOD) from the giant freshwater prawn Macrobrachium rosenbergii. 1662 6

Manganese superoxide dismutase (MnSOD, SOD2) is an essential primary antioxidant enzyme which converts superoxide radical to hydrogen peroxide within the mitochondrial matrix. MnSOD plays a prominent role in protection against many apoptotic stimuli. Its absence may therefore impair the cellular redox balance and enhance apoptosis. Our data show that in Jurkat T cells, following oligomerization of the Fas receptor, MnSOD is selectively degraded during apoptosis. In the presence of cycloheximide, an inhibitor of protein synthesis, the rates of cell death and MnSOD degradation were accelerated. Fas-induced MnSOD cleavage was partially inhibited in the presence of the pan-caspase inhibitor, z-VAD-fmk. MnSOD in the mitochondrial fractions was cleaved in vitro by treatment with the cytosolic fraction of Fas-activated cells. Moreover, two possible cleavage sites of recombinant hMnSOD by direct interaction with recombinant caspase-3 were noted. Cellular and mitochondrial factors were found to be necessary for the interaction. These factors include intracellular mobilization of calcium. Our data indicate that inactivation of MnSOD in receptor-mediated apoptosis by caspase-specific degradation would render the mitochondria sensitive to the steady-state production of superoxide, decrease the steady-state flux of H(2)O(2), expedite the loss of mitochondrial function, and potentiate apoptosis.
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PMID:Manganese superoxide dismutase inactivation during Fas (CD95)-mediated apoptosis in Jurkat T cells. 1715 82


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