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

This study presents an e.s.r. assay for superoxide dismutase (SOD). Enzymic reactions were studied in which Cu,Zn-SOD, Mn-SOD and Fe-SOD each competed with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) for superoxide anion (O2-) at pH 7.8 O2- from dissolved KO2 (potassium superoxide) in dimethyl sulphoxide was added directly to the enzyme solutions containing DMPO. The results show that, in this competition reaction system, the kinetics of the reactions between the enzymes and O2- follow a function y = f[( SOD]0.5). The rate constant, kSOD = 6.4 x 10(9) M-1. S-1, determined for Cu,Zn-SOD is approximately an order of magnitude larger than those for Mn-SOD and Fe-SOD. A comparative study of reported SOD mimics, including Mn2+, MnO2-desferrioxamine mesylate (Desferal) and MnO2-Desferal-ascorbate, was done. The results show that solutions of these complexes are approximately three orders of magnitude less active than Cu,Zn-SOD and approximately two orders of magnitude less active than Mn-SOD or Fe-SOD. The results also suggest that the reactivity toward O2- in solutions of these complexes originates from the Mn2+ present and not from the MnO2-Desferal complexes.
 ...
PMID:Kinetics of superoxide scavenging by dismutase enzymes and manganese mimics determined by electron spin resonance. 131 Nov 75

The effects of unilateral nerve transection on manganese and copper/zinc superoxide dismutase (Mn-SOD and Cu/Zn-SOD) mRNA levels in the facial nucleus were studied by in situ hybridization. An increase of Mn-SOD mRNA levels was first seen in the ipsilateral facial nucleus 12 h after axotomy, and was most pronounced at 4-7 days after this procedure; by 56 days, the increase disappeared. There was no change in Cu/Zn-SOD mRNA levels at any time after axotomy. We further confirmed, by immunohistochemistry, that the increase in Mn-SOD transcription was followed by protein synthesis. These results are suggestive of an important role for Mn-SOD in defense, regeneration and recovery responses following nerve transection.
 ...
PMID:Differential regulation of manganese and copper/zinc superoxide dismutases by the facial nerve transection. 139 56

Superoxide dismutases are enzymes that defend against oxidative stress through decomposition of superoxide radical. Escherichia coli contains two highly homologous superoxide dismutases, one containing manganese (MnSOD) and the other iron (FeSOD). Although E. coli Mn and FeSOD catalyze the dismutation of superoxide with comparable rate constants, it is not known if they are physiologically equivalent in their protection of cellular targets from oxyradical damage. To address this issue, isogenic strains of E. coli containing either Mn or FeSOD encoded on a plasmid and under the control of tac promoter were constructed. SOD specific activity in the Mn and FeSOD strains could be controlled by the concentration of isopropyl beta-thiogalactoside in the medium. The tolerance of these strains to oxidative stress was compared at equal Mn and FeSOD specific activities. Our results indicate that E. coli Mn and FeSOD are not functionally equivalent. The MnSOD is more effective than FeSOD in preventing damage to DNA, while the FeSOD appears to be more effective in protecting a cytoplasmic superoxide-sensitive enzyme. These data are the first demonstration that Mn and FeSOD are adapted to different antioxidant roles in E. coli.
 ...
PMID:Functional differences between manganese and iron superoxide dismutases in Escherichia coli K-12. 144 75

Evidence is reported that liver manganese deficiency, whether artificially produced by the administration of a Mn-deficient diet, or physiologically occurring in the neonatal life, in mice and rats respectively, causes the down-regulation of the manganese-containing superoxide dismutase at (pre)-transcriptional level. These observations, in addition to previous data concerning Mn-deficiency and the low level of expression of MnSOD in Morris hepatomas, strongly support the role played by the metal ion in the control of the MnSOD by a mechanism of gene activation. While the molecular events taking place in such regulation are not yet identified, the involvement of reactive oxygen species (ROS) as second messengers in the activation of specific transcription factors is suggested.
 ...
PMID:Transcriptional regulation of MnSOD by manganese in the liver of manganese-deficient mice and during rat development. 148 98

Four experiments were done to characterize the interactions of copper, iron, and ascorbic acid with manganese in rats. All experiments were factorially arranged Dietary Mn concentrations were less than 1 micrograms/g (Mn0) and 50 micrograms/g (Mn+). Dietary Cu was less than 1 mg/g (Cu0) and 5 micrograms/g (Cu+); dietary Fe was 10 micrograms/g (Fe10) and 140 micrograms/g (Fe140). Ascorbic acid (Asc) was not added to the diet or added at a concentration of 10 g/kg diet. Experiment 1 had two variables, Mn and Cu; in Experiment 2, the variables were Mn and Asc. In Experiment 3, the variables were Mn, Cu, and Asc; in Experiment 4, they were Mn, Cu, and Fe. Definite interactions between Mn and Cu were observed, but they tended to be less pronounced than interactions between Mn and Fe. Cu depressed absorption of 54Mn and accelerated its turnover. In addition, adequate Cu (Cu+), compared with Cu0, depressed liver, plasma, and whole blood Mn of rats. Absorption of 67Cu was higher in animals fed Mn0 diets than in those fed Mn+. Ascorbic acid depressed Mn superoxide dismutase activity and increased Cu superoxide dismutase activity in the heart. The addition of ascorbic acid to the diet did not affect Mn concentration in the liver or blood. Absorption of 54Mn was depressed in rats fed Fe140 compared with those fed Fe10. Interactions among Fe, Cu, and Mn resulted in a tendency for Mn superoxide dismutase activity to be lower in rats fed Fe140 than in rats fed Fe10. Within the physiologic range of dietary concentrations, Mn and Cu have opposite effects on many factors that tend to balance one another. The effects of ascorbic acid on Mn metabolism are much less pronounced than effects of dietary Cu, which in turn affects Mn metabolism less than does Fe.
 ...
PMID:Effects of copper, iron, and ascorbic acid on manganese availability to rats. 154 27

We examined the effect of lipopolysaccharide (LPS) treatment on the expression of manganese and copper/zinc superoxide dismutase (MnSOD and Cu/ZnSOD) mRNA and protein in resident peritoneal macrophages and lung endothelial cells derived from LPS-sensitive (LPS-s) and LPS-resistant (LPS-r) mice. Macrophages from both LPS-s and LPS-r mice treated with LPS for 24 h produced increased levels of MnSOD mRNA and protein. In contrast, levels of lung endothelial cell MnSOD mRNA and protein from LPS-s mice were increased by LPS treatment, while no increases in these parameters were observed in endothelial cells from LPS-r mice. Tumor necrosis factor-alpha (TNF alpha) treatment, however, did increase levels of MnSOD mRNA in both LPS-s and LPS-r endothelial cells to an equal extent. Both macrophage and endothelial cell Cu/ZnSOD mRNA and protein levels were not significantly affected by LPS treatment. These results demonstrate that the mutation that affects susceptibility to LPS in LPS-r mice exerts a differential influence on MnSOD inducibility in a cell specific manner.
 ...
PMID:Mn and Cu/Zn SOD expression in cells from LPS-sensitive and LPS-resistant mice. 155 15

Anaerobically grown Escherichia coli contain an enzymatically active iron superoxide dismutase (Fe2-FeSOD) and an inactive iron-substituted manganese superoxide dismutase (Fe2-MnSOD). The anaerobic electron sink, nitrate plus paraquat, enhanced biosynthesis of the MnSOD polypeptide, with accumulation of inactive Fe2-MnSOD. The oxidant, diamide, in contrast, allowed anaerobic production of the active forms of MnSOD, i.e. Mn2-MnSOD and Mn/Fe-MnSOD. Nutritional supplementation with Mn(II) favored occupancy of the MnSOD active site with manganese and allowed anaerobic accumulation of Mn2-MnSOD in the absence of diamide. Enrichment of the anaerobic growth medium with Fe(II) both suppressed biosynthesis of the MnSOD polypeptide and inhibited formation of the active manganese-containing forms. A tac-sodA operon fusion was used to examine the effects of chelating agents and metals on maturation of nascent MnSOD, independent from the transcriptional effects these agents impose. Isopropyl-1-thio-beta-D-galactopyranoside (IPTG) elicited anaerobic biosynthesis of MnSOD, which accumulated as the inactive Fe2-MnSOD. Diamide, with IPTG, allowed formation of active Mn/Fe-MnSOD while 1,10-phenanthroline with IPTG resulted in accumulation of Mn2-MnSOD. These results suggest that iron participates in the redox-sensitive control of the formation of active MnSOD at two levels, i.e. that of transcription as well as that of maturation. During maturation of the nascent MnSOD polypeptide, iron and manganese compete for the metal-binding site; anaerobic conditions favor iron-binding, whereas oxidants, such as dioxygen or diamide, favor binding of manganese.
 ...
PMID:Transcriptional and maturational effects of manganese and iron on the biosynthesis of manganese-superoxide dismutase in Escherichia coli. 157 50

Human retinal pigment epithelium (RPE) contains two genetically distinct forms of superoxide dismutase (SOD) enzymes that scavenge harmful superoxide anions. Biochemical and immunochemical techniques were used to compare levels of copper-zinc- and manganese-containing forms of SOD (CuZn-SOD and Mn-SOD) in human adult and fetal RPE cells. It was found that Mn-SOD activity was higher in adult than fetal RPE cells, both in vivo and in vitro. Immunolocalization of Mn-SOD in cultured RPE cells showed a greater reactivity in the mitochondria of the adult cells. Primary cultures of adult RPE contained cells with various patterns of mitochondria as shown by immunolabeling for Mn-SOD. Adult RPE cells were more resistant to the effects of a superoxide generator, paraquat, which appeared to disrupt mitochondrial integrity as judged by staining with rhodamine 123. These results suggest that high levels of Mn-SOD protect mitochondria from oxidative damage that probably occurs with aging in the RPE.
 ...
PMID:Mitochondrial superoxide dismutase in mature and developing human retinal pigment epithelium. 158 97

We used rabbit antisera against manganese (Mn)-superoxide dismutase for immunohistochemical studies of localization in the rat neostriatum. Immunostaining was intense in large-sized neurons and several medium-sized neurons, but it was moderate to weak in other cells. Double immunostaining with monoclonal antibody to choline acetyltransferase or somatostatin demonstrated large-sized, Mn-SOD immunoreactive neurons to be cholinergic, and some medium-sized neurons which were intensely immunoreactive for Mn-SOD to contain somatostatinergic.
 ...
PMID:Localization of Mn-superoxide dismutase (Mn-SOD) in cholinergic and somatostatin-containing neurons in the rat neostriatum. 168 20

Studies in mice have suggested that both dietary Al excess and dietary Mn deficiency promote oxidative tissue damage. To determine if these factors can interact to produce functional nervous system damage, female mice (N = 10-12 per group) were fed diets with control or low Mn (35 or 3 micrograms Mn/g diet) and/or control or high Al (25 or 1000 micrograms Al/g diet, Al as Al lactate) content for a 90-day period. No overt signs of neurotoxicity were observed in any group. Excess Al produced a threefold Al accumulation in both liver and brain, a slight acceleration of growth, decreased motor activity, decreased grip strength, and decreased startle responsiveness. Manganese deprivation led to liver, brain, and femur Mn depletion and reduced liver MnSOD activity but no neurobehavioral changes. No interactive effects between Al excess and Mn deficiency were observed. Neither Al excess nor Mn deficiency altered brain or liver lipid peroxidation measures. This study suggests that (1) subchronic dietary Al at doses of 1000 micrograms Al/g diet produces elevated brain Al and altered neurobehavioral indices in adult mice; (2) brain lipid peroxidation is not altered by this treatment; (3) dietary Mn deficiency does not influence Al neurotoxicity in adult mice.
 ...
PMID:Effects of dietary aluminum excess and manganese deficiency on neurobehavioral endpoints in adult mice. 173 44


1 2 3 4 5 6 7 8 9 10 Next >>