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) molecules occur in all cells exposed to an oxygen-containing environment, including retinal pigment epithelial (RPE) cells. Previous studies of nonhuman RPE have either probed specifically for copper-zinc-containing SOD (CuZn-SOD) or have not distinguished between CuZn-SOD and the SOD molecule that contains manganese (Mn-SOD). The authors used specific enzymatic assays and immunologic probes, both in vivo and in vitro, to show that human RPE cells contain both CuZn-SOD and Mn-SOD. The CuZn-SOD had a diffuse cytosolic distribution, whereas the Mn form was located primarily in the mitochondria. The role of SODs in protecting the chorioretinal complex against oxidative damage and with regard to aging processes is not well understood and warrants further investigation, and the two cellular forms of SOD should be considered in future studies.
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PMID:Human retinal pigment epithelium contains two distinct species of superoxide dismutase. 226 90

Three isozymes of superoxide dismutase (SOD) have been identified and characterized. The iron and manganese isozymes (Fe-SOD and Mn-SOD, respectively) show extensive primary sequence and structural homology, suggesting a common evolutionary ancestor. In contrast, the copper/zinc isozyme (CuZn-SOD) shows no homology with Fe-SOD or Mn-SOD, suggesting an independent origin for this enzyme. The three isozymes are unequally distributed throughout the biological kingdoms and are located in different subcellular compartments. Obligate anaerobes and aerobic diazotrophs contain Fe-SOD exclusively. Facultative aerobes contain either Fe-SOD or Mn-SOD or both. Fe-SOD is found in the cytosol of cyanobacteria while the thylakoid membranes of these organisms contain a tightly bound Mn-SOD. Similarly, most eukaryotic algae contain Fe-SOD in the chloroplast stroma and Mn-SOD bound to the thylakoids. Most higher plants contain a cytosol-specific and a chloroplast-specific CuZn-SOD, and possibly a thylakoid-bound Mn-SOD as well. Plants also contain Mn-SOD in their mitochondria. Likewise, animals and fungi contain a cytosolic CuZn-SOD and a mitochondrial Mn-SOD. The Mn-SOD found in the mitochondria of eukaryotes shows strong homology to the prokaryotic form of the enzyme. Taken together, the phylogenetic distribution and subcellular localization of the SOD isozymes provide strong support for the hypothesis that the chloroplasts and mitochondria of eukaryotic cells arose from prokaryotic endosymbionts.
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PMID:Phylogenetic distribution of superoxide dismutase supports an endosymbiotic origin for chloroplasts and mitochondria. 226 71

We have demonstrated a dramatic induction of manganese superoxide dismutase (Mn-SOD) mRNA levels in response to lipopolysaccharide (LPS), interleukin-1, and tumor necrosis factor in pulmonary epithelial cells. These stimuli had no effect on the corresponding mRNA levels for the copper/zinc (Cu/Zn)-SOD. Identical treatments of pulmonary fibroblast cells with LPS showed only minor changes in the Mn-SOD mRNA levels demonstrating a cell type-specific effect for this acute inflammatory mediator. Furthermore, we have shown that hyperoxia has no effect within 24 h on Mn-or Cu/Zn-SOD mRNA levels in either fibroblasts or epithelial cells. The induction of Mn-SOD mRNA levels by LPS is completely inhibited by actinomycin. Treatment of cells with cycloheximide causes an induction equal to that for LPS, whereas co-treatment with cycloheximide and LPS resulted in a "super induction." This data is strongly suggestive of an important role for the Mn-SOD in the acute inflammatory response.
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PMID:Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response. 240 41

1. A number of dietary sugars are known to mediate the effects of copper deficiency. The effects of lactose (compared with sucrose) and a dietary Cu deficiency on hepatic and cardiac antioxidant enzyme activities and tissue mineral element status were investigated in the rat. 2. Groups (n 6) of male weanling Wistar rats were provided ad lib. with deionized water and diets containing sucrose (580 g/kg) or sucrose and lactose (387 g/kg and 193 g/kg respectively) with either control (12.0 mg/kg) or deficient (1.5 mg/kg) quantities of Cu for 77 d. 3. Animals consuming the low-Cu diets exhibited significantly decreased tissue Cu levels (P less than 0.01), hepatic and cardiac cytochrome c oxidase (EC 1.9.3.1, CCO) activities (P less than 0.01 and P less than 0.001 respectively) and hepatic Cu-zinc superoxide dismutase (EC 1.15.1.1, CuZnSOD) activity (P less than 0.05). The low-Cu diets also significantly decreased cardiac manganese superoxide dismutase (EC 1.15.1.1, MnSOD), catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9, GSH-Px) activities (P less than 0.01, P less than 0.05 and P less than 0.001 respectively). 4. Hepatic Mn was significantly increased in both lactose-fed (P less than 0.001) and Cu-deficient (P less than 0.01) animals. These increases were unrelated to hepatic MnSOD activity. Cardiac Zn was significantly (P less than 0.01) increased in Cu-deficient animals. 5. Lactose feeding resulted in significantly increased cardiac CCO activity (P less than 0.001) but significantly decreased hepatic CuZnSOD (P less than 0.05), catalase (P less than 0.01) and GSH-Px (P less than 0.001) activities. 6. The activities of lactose dehydrogenase (EC 1.1.1.27, LDH) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PDH) were found to be significantly (P less than 0.05 and P less than 0.01 respectively) increased in Cu-deficient animals and G6PDH activity was significantly (P less than 0.01) decreased as a result of lactose consumption. 7. The observed changes in antioxidant enzyme activities associated with both Cu deficieny and lactose consumption may have important implications for the development of free radical mediated cell damage. However, no significant differences in either hepatic or cardiac levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation, were found.
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PMID:Effects of copper deficiency on hepatic and cardiac antioxidant enzyme activities in lactose- and sucrose-fed rats. 253 51

Mg2+, Ca2+, Mn2+, Zn2+, and Cu content of neurons from chick embryo cortex cultivated in chemically defined serum free growth medium was determined by energy dispersive X-ray fluorescence and atomic absorption spectroscopy. The intracellular volume of cultured neurons was determined to be 2.73 microliters/mg. Intracellular Mn2+, Fe2+, Zn2+, and Cu2+ in the cultivated neurons were 100-200 times the concentrations in the growth medium: Mg2+ and Ca2+ were 0.9 and 1.7 mM respectively, around 20 fold higher than in growth medium. Mg2+, Fe2+, Cu2+ and Zn2+ concentrations in neurons were in the range of ca. 300-600 microM, approximately 2-3 times the values previously reported in glial cells; Ca2+ and Mn2+ content of the neurons were higher by 5 and 10 fold respectively compared to glial cells. In neurons, the subcellular distribution of Fe2+, Cu2+, and Mn2+ follows the rank order: cytosol greater than microsomes greater than mitochondria; for Zn2+ the distribution differs as following: cytosol greater than mitochondria greater than microsomes. Determination of the superoxide dismutase activities in the cultivated neurons indicated that the Mn2+ linked activity predominates whereas, the Cu-Zn dependent enzyme is dominant in glial cells. Enrichment of the culture medium with Mn2+ to 2.5 microM enhanced the Mn-SOD by approximately 33% but the Cu2+-Zn2+ enzyme activity was not modified. The high Mn2+ content, the capacity to accumulate Mn2+, and the predominancy of the Mn-SOD form observed in neurons is in accord with a fundamental functional role for this metal ion in this type of brain cells.
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PMID:Levels and sub-cellular distribution of physiologically important metal ions in neuronal cells cultured from chick embryo cerebral cortex. 323 9

Effects of complete ischemia on levels of antioxidative enzymes including copper-zinc (CuZn) superoxide dismutase (SOD), manganese (Mn)-SOD, and glutathione peroxidase (GSH-Px) were studied in rat brain regions at 30 and 60 min following decapitation. CuZn-SOD activities were significantly decreased in cerebral cortex and hippocampus at both time points whereas the enzyme activities were decreased at 60 min in cerebellum and caudate areas. The reduction of Mn-SOD activities followed the same pattern of CuZn-SOD in various brain regions. However, GSH-Px activities in these brain regions were not affected by decapitation ischemia. These data suggest that the reduction of CuZn-SOD and Mn-SOD activities during ischemia, in conjunction with the significant decrease in the contents of alpha-tocopherol and other endogenous antioxidants, may compromise the brain's ability to defend against the toxic effects of superoxide radicals formed by ischemia and by subsequent reoxygenation.
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PMID:Reduction of activities of superoxide dismutase but not of glutathione peroxidase in rat brain regions following decapitation ischemia. 335 97

Studies of marginal zinc deficiency in rhesus monkeys have demonstrated that plasma Zn levels are often a poor indication of Zn status. To better assess the Zn status of these animals, we examined their liver concentration of Zn as well as of other minerals, metallothionein (MT), and superoxide dismutase (SOD). Liver-wedge biopsies were obtained from adult rhesus monkeys fed for 15 mo, either a control (100 micrograms Zn/g) or a marginally Zn deficient diet (4 micrograms/g; ZD). Liver Zn and MT concentrations were lower in ZD monkeys than in controls whereas iron concentration was higher in ZD monkeys than in controls. Liver copper, manganese, and magnesium concentrations and activities of CuZnSOD and MnSOD were similar in the two groups. Data from the groups were pooled for regression analysis. Measurement of liver Zn and MT concentrations are useful in the assessment of the effects of long-term Zn deprivation in primates.
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PMID:Studies of marginal zinc deprivation in rhesus monkeys. III. Use of liver biopsy in the assessment of zinc status. 337 2

Both the copper-zinc (CuZn) and the manganese (Mn) containing superoxide dismutases (SOD) have been immunolocalized in rat liver sections using protein A-gold labeling on ultrathin cryosections. The CuZnSOD was found to distribute uniformly throughout the nuclear and cytoplasmic matrix. The CuZn enzyme was excluded from membrane-bound compartments such as the nuclear envelope, endoplasmic reticulum, Golgi elements, secretory vesicles, and mitochondria. The primary exception was that lysosomes frequently labeled heavily for CuZnSOD. The lysosomal nature of these membrane-bound bodies was confirmed by double immunolabeling with a lysosomal enzyme, cathepsin-D. The MnSOD was located in mitochondria, particularly the matrix between the cristae. Light but distinct labeling for the MnSOD occurred in the cytoplasmic matrix.
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PMID:Intracellular localization of the copper-zinc and manganese superoxide dismutases in rat liver parenchymal cells. 374 50

We have isolated a protein factor from rat liver which stimulates anthranilamide hydroxylation by the microsomes in the presence of NADPH and oxygen and showed this factor to contain Cu and Zn and to have superoxide dismutase activity [Biochim. Biophys. Acta 365, 148-157 (1974)]. In the present study, this protein factor was confirmed to be a superoxide dismutase (SOD) by comparison of the recovery of SOD activity with that of anthranilamide hydroxylation-stimulating activity at each step of its purification, by inhibition of SOD activity with NaCN and hydrogen peroxide (H2O2), and by recovery of the SOD activity of the protein factor after reconstitution with Cu2+ and/or Zn2+. At a given SOD activity level, there was no difference among the rat liver SOD, Cu,Zn-SOD from bovine erythrocytes, and Mn-SOD from Serratia marcescens in their ability to stimulate anthranilamide hydroxylation not only by rat liver microsomes, but also by the reconstituted cytochrome P-450-containing monooxygenase system. Rat liver SOD stimulated anthranilamide hydroxylation by the reconstituted system in proportion to its amount below a protein concentration of 1 microgram/ml. In anthranilamide hydroxylation by the reconstituted system without SOD, only a slight hydroxylase activity was found at the initial stage of the reaction and a marked increase in the amounts of NADPH oxidized and H2O2 formed was observed after a lag time. In the presence of rat liver SOD, however, the hydroxylase activity was markedly and continuously increased almost proportionally to reaction time with a concomitant decrease in the amounts of NADPH oxidized and H2O2 formed. In addition, a trace of 3-OH anthranilamide, one of the products, not only stimulated NADPH-dependent H2O2 formation in the reconstituted system, but also inhibited the apparent reduction of cytochrome P-450 by NADPH in the reconstituted system. These effects of 3-OH anthranilamide were diminished by rat liver SOD. When a trace of 3-OH anthranilamide were added to a system composed of NADPH-cytochrome c (P-450) reductase and NADPH, H2O2 formation and NADPH oxidation were markedly stimulated. However, on addition of 3-OH anthranilamide to the system containing rat liver SOD, no stimulation on either H2O2 formation or NADPH oxidation was found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of cytosolic superoxide dismutase as a stimulator in anthranilamide hydroxylation by a microsomal monooxygenase system in rat liver. 644 2

Activities of the copper-zinc- and manganese-containing superoxide dismutase enzymes (CuSOD and MnSOD) were studied in tissues of the sheep to determine the dependence of these activities on sheep age, and their relationship to tissue and dietary mineral concentrations. Tissue samples were obtained from day-old through 16-week-old lambs from flocks grazing pastures normal or high in copper and manganese, and from adult sheep. In liver, lung, heart, kidney and skeletal muscle, activities of CuSOD and MnSOD in day-old and week-old lambs were only half those measured in 16-week-old and adult sheep. Activities in 4-week-old lambs were intermediate between these two groups except for heart tissue, in which activities were not increased until lambs were 16 weeks old. For all age groups, heart and skeletal muscle had low activities of CuSOD. Minimal age-related changes were observed for CuSOD activities in erythrocyte and brain tissues. The low enzyme activities evident in most tissues of day-old lambs, occurred in the presence of apparently adequate tissue copper and manganese concentrations. Concentrations of these minerals in lamb tissues were equal to or greater than those observed in older sheep and although these concentrations increased considerably with increased pasture mineral concentrations, enzyme activities were unchanged. Age-related increases in tissue CuSOD and MnSOD activities, occurring as normal developmental processes, may be important factors in diseases attributed to uncontrolled tissue peroxidation in sheep.
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PMID:Age-related changes in activities of the superoxide dismutase enzymes in tissues of the sheep and the effect of dietary copper and manganese on these changes. 648 83


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