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) from extracts of anaerobically maintained Bacteroides thetaiotaomicron was a dimer of equally sized 23,000-molecular-weight monomers joined noncovalently. A preparation with a specific activity of 1,200 U/mg contained 1.1 g-atom of Fe, 0.6 g-atom of Zn, and less than 0.05 g-atom of Mn per mol of dimer. The apoprotein, prepared by dialysis of iron-SOD in 5 M guanidinium chloride-20 mM 8-hydroxyquinoline, had no superoxide-scavenging activity when renatured without exogenous metal. Enzymatic activity was restored to the denatured apoprotein by dialysis against either 1 mM Fe(NH4)2 or 1 mM MnCl2 in 20 mM Tris (pH 7.0). The Fe-reconstituted enzyme and the native enzyme were inhibited approximately 50% by 0.2 mM NaN3, whereas the Mn-reconstituted enzyme was inhibited 60% by 10 mM NaN3. Aeration of the anaerobic cells resulted in a fourfold induction of an azide-resistant SOD. The enzyme (43,000 molecular weight) isolated from aerated cells was a dimer of equally sized subunits. The metal content was 1.0 g-atom of Mn, 0.55 g-atom of Fe, and 0.3 g-atom of Zn per mol of dimer. Enzymatic activity of the denatured apoprotein from this enzyme was also restored on addition of either iron or manganese. The constitutive Fe-SOD and the O2-induced Mn-SOD, tested alone and in combination, migrated identically on acrylamide gels, had similar amino acid compositions, and had alanine as the sole N-terminal amino acid. These data are consistent with the synthesis of a single apoprotein in either anaerobically maintained or oxygenated cells. We have observed a similar phenomenon with SOD from Bacteroides fragilis (E. M. Gregory, Arch. Biochem. Biophys. 238:83-89, 1985).
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PMID:Isolation and reconstitution of iron- and manganese-containing superoxide dismutases from Bacteroides thetaiotaomicron. 370 Mar 36

We report Mn superoxide dismutase (SOD) protein and activity in a patient with familial autosomal recessive Lewy body-negative parkinsonism in comparison with patients with sporadic Parkinson's disease (PD) and controls. We recently proved linkage of this family with markers of chromosome 6 at 6q25.2-27, which included the Mn SOD gene. We used a novel polymorphic mutation at -9 position of the signal peptide of the Mn SOD precursor protein, which caused valine to alanine substitution. All the affected members of this family showed homozygosity for alanine, whereas nonaffected members, sporadic PD patients, and the control subjects studied showed either heterozygosity of alanine and valine or homozygosity of valine. The Mn SOD activity of this familial patient was the highest among the PD patients and the control subjects studied, and an abundant expression of Mn SOD was found in the substantia nigra. The molecular weight of Mn SOD protein by Western blotting of this patient was essentially similar to that of PD patients and the control subjects. High Mn SOD activity may constitute a genetic risk factor in this familial patient. The difference in the signal peptide sequence may affect the expression of Mn SOD within mitochondria; however, it is unlikely that loss of function type Mn SOD mutation is the cause of this familial parkinsonism. Mn SOD in sporadic PD patients was similar to that in controls.
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PMID:Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson's disease and control. 937 4

A mangano-superoxide dismutase (EC 1.15.1.1) was purified to homogeneity from a strain of alkaliphilic Bacillus for the first time. The purified protein, with an isoelectric point of pH 4.5, had a molecular mass of approximately 50 kDa and consisted of two identical subunits (25 kDa). The N-terminal amino acid sequence was Ala-Tyr-Lys-Leu-Pro-Glu-Leu-Pro-Tyr-Ala-Ala-Asn-Ala-Leu-Glu-Pro-His-Ile- Asp-Glu-Ala. The optimum pH and temperature for the reaction were 7.5 and 35 degrees C, respectively. The properties of the superoxide dismutase were compared with those of the enzyme from thermophilic Bacillus stearothermophilus.
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PMID:Purification and properties of mangano-superoxide dismutase from a strain of alkaliphilic Bacillus. 968 Mar 5

Two polymorphisms of the MnSOD gene, Ile58Thr and Ala9Val, have been associated with Parkinson disease (PD). The Ile58Thr amino acid exchange affects the stability at the tetrameric interface of the enzyme and reduces the enzymatic activity of MnSOD while the Ala/Val substitution at position -9 of the mitochondrial targeting sequence (MTS) may lead to misdirected intracellular trafficking. We have analyzed 63 German Caucasian PD patients for possible sequence variation in the MTS as well as in exon 3 of the MnSOD gene. All 63 PD patients analyzed exhibited a T at nucleotide position 5777 in exon 3 of the MnSOD gene corresponding to ATA, or Ile at the peptide level, and no other sequence variants were found. In addition, both alleles of the Ala9Val polymorphism in the MTS of MnSOD were equally distributed between German PD patients and controls excluding this gene variant as a risk factor for PD in Caucasian subjects.
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PMID:Analysis of mitochondrial targeting sequence and coding region polymorphisms of the manganese superoxide dismutase gene in German Parkinson disease patients. 1004 82

In contrast to CuZn superoxide dismutase (SOD), only a very limited number of mutations have been described in MnSOD. One interesting example is a polymorphism (Ala-9Val) in the mitochondrial targeting sequence of this radical-scavenging enzyme. We have studied the Ala-9Val polymorphism in various ethnic groups by means of the oligonucleotide ligation assay. There were significant variations in this unique polymorphism between three different language groups: Baltic (Lithuanians), Finnic (Finns and Saamis) and Germanic (Swedes). The Ala frequency in an Asiatic population (Chinese) was significantly lower than in most European populations. This polymorphism may affect the mitochondrial targeting rate of MnSOD which may result in mitochondrial damage with implication in various late-onset neurological diseases.
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PMID:Ethnic variation in the mitochondrial targeting sequence polymorphism of MnSOD. 1043 79

There has been increasing evidence that deranged superoxide dismutase (SOD) activities might be a risk factor for schizophrenia and/or tardive dyskinesia (TD). In the present study, we investigated the genetic association between a functional polymorphism (Ala-9Val) in the human manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39 with TD and 153 without TD; 141 controls). No significant differences in the allelic or genotypic distribution between schizophrenics and controls were observed. However, we did find a significant difference in genotypic distribution between schizophrenics with and those without TD (p =. 03). Moreover, decreased -9Ala (mutant) allele was found among patients with TD (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In conjunction with previous findings of increased free radicals and decreased SOD activities in TD subjects, these results suggest that the -9Ala (high activity) MnSOD allele may play a role in protecting against susceptibility to TD in schizophrenics.
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PMID:Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskinesia. 1088 43

That tardive dyskinesia (TD) may have its origins in free-radical toxicity has stimulated investigations into one enzyme important in the control of oxidative free radicals: superoxide dismutase (SOD). The manganese-containing form of this enzyme (MnSOD) is the major superoxide scavenger in mitochondria; a weak association between a functional genetic polymorphism (Ala-9Val) in the mitochondrial targeting sequence (MTS) of this enzyme and TD has been reported in a Japanese population. We have undertaken to determine both the plasma activity of MnSOD and the association of the Ala-9Val polymorphism in a well-matched series of male Chinese schizophrenic patients with (n=42) and without (n=59) TD, and normal male controls (n=50). MnSOD activity was elevated in the TD subjects over those without TD (P<0.05) and normal controls (P<0.05), an effect that was independent of age, age at first antipsychotic treatment, drug dosage and duration of illness. A significant positive correlation between total AIMS score and MnSOD activity was also observed (P<0.0001). No significant reduction in the frequency of the Ala allele was observed in the TD group (0.14) below non-TD (0.18) or control subjects (0.17); nor was there any relationship between MnSOD activity and the polymorphism. There was no difference between the mean AIMS scores for the two genotypes (V/V and A/V) in the TD group. We conclude that while we have further evidence of a disturbance in the mechanisms regulating oxidative free radicals in TD, this effect is not under the control of the genetic polymorphism investigated here.
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PMID:The increased activity of plasma manganese superoxide dismutase in tardive dyskinesia is unrelated to the Ala-9Val polymorphism. 1212 99

Mutations of the superoxide dismutase (SOD) genes are associated with neoplastic and non-neoplastic diseases. However, the existence of polymorphic mutations of manganese SOD (Mn-SOD) has not been explored in squamous cell carcinoma (SCC) cells or in normal cells. In the present study, we examined mutations in the 5' flanking region of the Mn-SOD gene and Mn-SOD mRNA using 10 human oral SCC (OSC) cell lines and intact lymphocytes obtained from 10 healthy donors and one patient with OSC. The polymerase chain reaction products of DNA obtained from lymphocytes revealed insertions at many sites (-1833, -1575, -1093, -1056, -325, -318, and -310) in 10 of the 11 donors. Transitions and (or) transversions were also observed at -1638 and -216 in lymphocytes from six donors and one donor, respectively. In DNA obtained from OSC cells, insertions and transitions and (or) transversions were more frequent than those in DNA from lymphocytes. In addition, deletions at -1341 and -1288 were observed in all lines except for one line. In these mutations, the transcription factor binding sites were not involved except for the AP-2 binding site (-102) in three cell lines. In Mn-SOD mRNA, Val at -9 position was varied to Ala in lymphocytes from two donors and three OSC cell lines, respectively. In the remaining cell lines, Mn-SOD mRNA from lymphocytes and OSC cell lines revealed heterozygosity (Ala/Val) and homozygosity (Val/Nal), respectively. The Mn-SOD activities in lymphocytes were 3.8-5.8 x 10(-4) U/10(6) cells and the activities in OSC cell lines were 1.8-8.3 x 10(-4) U/10(6) cells. These Mn-SOD activities were not correlated with the mutations of DNA and mRNA. From these results, it is indicated that polymorphic mutations of Mn-SOD exist in human normal cells and that the deletions might be obtained in the course of malignant transformation of OSC although decrease in Mn-SOD activity is not involved in the transformation.
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PMID:Polymorphic mutations of the Mn-SOD gene in intact human lymphocytes and oral squamous cell carcinoma cell lines. 1268 35

Lung epithelial cells produce increased reactive oxygen species (ROS) after hypoxia exposure, and they are more susceptible after hypoxia to injury by agents that generate superoxide [O2-; e.g., 2,3-dimethoxy-1,4-naphthoquinone (DMNQ)]. Cellular GSH and MnSOD both decrease in hypoxic lung epithelial cells, altering the redox state. Because ROS participate in signaling pathways involved in cell death or survival, we tested the hypothesis that mitogen-activated protein kinases (MAPK) were involved in a protective response against cellular injury during reoxygenation. Human lung epithelial A549 cells were incubated in hypoxia (<1% O2 for 24 h) and then reoxygenated by return to air. p38mapk and MKK3 phosphorylation both decreased after hypoxia. During reoxygenation, cells were incubated with DMNQ (0-50 microM), a redox cycling quinone that produces O2-. Hypoxia preexposure significantly increased epithelial cell lysis resulting from DMNQ. Addition of the p38mapk inhibitors SB-202190 or SB-203580 markedly increased cytotoxicity, as did the mitogen/extracellular signal-regulated kinase (MEK) 1/2 inhibitor PD-98059 (all 10 microM), suggesting a protective effect of downstream molecules activated by the kinases. Transfection of A549 cells with a dominant active MKK3 plasmid (MKK3[Glu]) partially inhibited cytolysis resulting from DMNQ, whereas the inactive MKK3 plasmid (MKK3[Ala]) had less evident protective effects. Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from O2-.
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PMID:p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after hypoxia. 1467 18

Oxidative stress plays a key role in the development of microvascular complications of diabetes mellitus (DM). Antioxidant enzymes protect against the rapid onset of diabetic polyneuropathy (DPN) by reducing oxidative stress. Genetic variations that affect activity or expression levels of the antioxidant enzymes may therefore be associated with susceptibility to DPN. We examined polymorphic markers Ala(-9)Val in SOD2 gene and Arg213Gly in SOD3 gene for possible relation to DPN in Russian type 1 diabetic patients. Four hundred Russian white patients with type 1 diabetes were studied using neurological examination according to recommendations of the San Antonio Conference on Diabetic Neuropathy. Two groups were formed from the general sample. Definition of frequency distribution of the polymorphic markers was performed in these groups using the polymerase chain reaction. Genes encoding the enzymes Mn-SOD and extracellular superoxide dismutase (EC-SOD) were found to be associated with the pathogenesis of DPN.
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PMID:Predisposing genetic factors for diabetic polyneuropathy in patients with type 1 diabetes: a population-based case-control study. 1470 72


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