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)

HA-1 hamster fibroblasts receiving fresh media every 24 h were continuously passaged in progressively increasing O2 concentrations for 18 mo (designated O2R95). These cells were significantly more resistant than parental HA-1 to clonogenic inactivation mediated by 95% O2 without media replacement. The O2R95 cell line exhibited increases in the activities of catalase (CAT), Mn superoxide dismutase (MnSOD), Cu,Zn superoxide dismutase (Cu,Zn SOD), and glutathione peroxidase (GPx). O2R95 cells demonstrated uniformly distributed increased staining for CAT, MnSOD, Cu,Zn SOD, and GPx proteins, as determined by immunohistochemistry. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a toxic byproduct of lipid peroxidation implicated in mechanisms of O2 toxicity, was examined in HA-1 and O2R95 cell lines. O2R95 cells were significantly more resistant to 4HNE cytotoxicity, which was accompanied by a significant increase in 4HNE metabolism. O2R95 cells also demonstrated an increase in total glutathione (GSH) and glutathione S-transferase (GST) activity, an enzymatic system believed to be involved with 4HNE metabolism. Furthermore, homogenates from O2R95 cells consumed greater quantities of 4HNE in the presence of NADPH (but not NADH, NAD+, or NADP+), suggesting that an enzyme(s) utilizing NADPH contributes to 4HNE metabolism, resistance to 95% O2 and 4HNE as well as increased total GSH, antioxidant enzyme activities, and NADPH-dependent metabolism of 4HNE, persisted in O2R95 cells for 75 days of growth in 21% O2. These findings are compatible with the hypothesis that aldehydic byproducts of lipid peroxidation contribute to mechanisms of O2 toxicity and the selective pressure exerted by exposure of cells to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A stable O2-resistant cell line: role of lipid peroxidation byproducts in O2-mediated injury. 161 58

Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1), and interleukin-6 (IL-6) are multifunctional cytokines produced by a number of cells in response to endotoxin. We have previously demonstrated (M.-F. Tsan, J. E. White, T. A. Santana, and C. Y. Lee. J. Appl. Physiol. 68: 1211-1219, 1990, and M.-F. Tsan, C. Y. Lee, and J. E. White. J. Appl. Physiol. 71: 688-697, 1991) that tracheal insufflation of 5 micrograms of TNF-alpha or 1 microgram of IL-1 markedly protects rats against O2 toxicity and enhances pulmonary Mn superoxide dismutase (Mn SOD) activity. We now report that TNF-alpha and IL-1 at subprotective doses, e.g., 1 and 0.2 micrograms, respectively, act synergistically in protecting rats against O2 toxicity. Likewise, TNF-alpha and IL-1 at 0.005 microgram/ml each act synergistically in enhancing endothelial cell Mn SOD, but not Cu,Zn SOD mRNA levels. IL-6 at 5 or 10 micrograms provides no protective effect in rats against O2 toxicity and at up to 0.5 microgram/ml has no apparent effect on endothelial cell Mn or Cu,Zn SOD mRNA levels. However, IL-6 markedly enhances TNF-alpha- and IL-1-induced increases in Mn SOD mRNA levels and O2 tolerance. These results support an important role of Mn SOD in the protection against O2 toxicity.
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PMID:IL-6 enhances TNF-alpha- and IL-1-induced increase of Mn superoxide dismutase mRNA and O2 tolerance. 163 26

A method for copper- and manganese-containing superoxide dismutase (Cu- and MnSOD) assay in tissue homogenates such as liver and brain, based on the measurement of the longitudinal nuclear relaxation time (T1) of F-, has been developed as a preliminary approach to in vivo measurement of these enzymes. The relaxation rate of F-, which increases linearly with the SOD concentration, also depends on the oxidation state of the metal ion present in the active site of the enzyme. The relaxivity values of the oxidized, reduced and turnovering CuSOD were found to be 9.6 x 10(6), much less than 1 x 10(2) and 5.2 x 10(6) M-1 s-1, respectively, while for MnSOD the corresponding values were 2.9 x 10(6), 4.2 x 10(6) and 3.6 x 10(6) M-1 s-1, respectively. These high relaxivity values allow the detection of SODs in brain and liver homogenates where, under aerobic conditions, these enzymes appear in the steady-state. The contribution of the two types of SOD to the F- relaxation rate in the homogenates was measured by addition of either diethyldithiocarbamate or cyanide, both of which selectively inhibit the CuSOD. The comparison between NMR and activity data confirmed the possibility of carrying out accurate and precise measurements of SODs in homogenates by NMR.
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PMID:NMR method for superoxide dismutase assay in brain and liver homogenates. 164 13

The SOD of Propionibacterium freudenreichii, ssp. shermanii belongs to a new group of SOD's capable of retaining activity with either Fe or Mn as active metal cofactor. Both enzymes exhibit identical secondary structure and immunological determinants. Hydrogen peroxide irreversibly inhibits both enzymes. The protein moiety of the Fe- and Mn-SOD could be digested with trypsin to a single active fragment.
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PMID:Comparative studies on a superoxide dismutase exhibiting enzymatic activity with iron and manganese as active cofactor. 164 91

Unsporulated oocysts of Eimeria tenella have high superoxide dismutase (SOD: superoxide:superoxide oxidoreductase, EC 1.15.1.1.) activity and contain several electrophoretically distinct forms of the enzyme, including two forms of Cu/Zn-containing SOD, two forms of Fe-SOD and two forms of Mn-SOD. SOD activity remains high during 12 h of sporulation but diminishes slowly during prolonged sporulation. Oocysts sporulated for 48 h have low levels of superoxide dismutase and contain only one form of the enzyme (Mn-SOD), which was also found in sporozoites. In vitro, sporozoites are oxidant-sensitive and die within minutes of superoxide radical (O2-) generation but SOD/catalase and mannitol protect sporozoites against oxidative damage. These data suggest that E. tenella sporulated oocysts and sporozoites lack soluble cytoplasmic SOD and that this deficiency may contribute to the oxidant sensitivity of the parasite.
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PMID:Superoxide dismutases in Eimeria tenella. 165 47

Two forms of superoxide dismutase, CuZn-SOD and MnSOD, have been investigated in the kidneys of streptozotocin-induced diabetic rats using both radio-immunoassay and immunoenzyme staining. The rats were killed 2, 8 and 12 weeks after the induction of diabetes mellitus and the kidneys excised. Two weeks after the induction of diabetes, the kidneys were hypertrophied because of the proliferation of renal tubular epithelium. However, the total CuZnSOD content of the kidneys did not increase and, because of the epithelial proliferation, the CuZnSOD concentration in each proximal tubular cell was decreased. Armanni-Ebstein lesions were found in the distal tubules 8 and 12 weeks after the induction of diabetes. The cells in these lesions were intensely stained for CuZnSOD, suggesting an adaptive response to the enhanced oxidative stress. The MnSOD staining in the thick ascending limbs of Henle's loops was enhanced in the diabetic kidneys, while that in the cortical tubules was unaltered. MnSOD was assumed to increase in response to hypermetabolism associated with the proliferation of renal tubules. This was most marked in the cells which were rich in mitochondria, again suggesting an adaptive response to enhanced oxidative stress induced by diabetes mellitus. The glomeruli of both the diabetic and control groups were not stained for SODs, and no significant microscopic change was found even 12 weeks after the induction of diabetes mellitus.
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PMID:Effect of diabetes mellitus induced by streptozotocin on renal superoxide dismutases in the rat. A radioimmunoassay and immunohistochemical study. 167 79

The antioxidant responses of human cell differentiation and membrane fusion are not known and may be important in understanding cellular response to injury in the human placenta. We studied the regulation of antioxidant enzymes in human trophoblasts which differentiate from mononucleated cellular trophoblasts to synctium in vivo and in culture. We characterized morphological and biochemical differentiation of cultured trophoblasts from term placenta in the presence or absence of serum, on different growth surfaces, and with a range of plating densities. Culture of cellular trophoblasts consistently and transiently induced the mRNAs of the mitochondrial antioxidant manganese superoxide dismutase (Mn SOD) but not the mRNAs for the antioxidant enzymes copper zinc SOD or catalase. Fibrin and type I collagen substrates modulated only the expression of the placental specific proteins, human chorionic gonadotropin, and human placental lactogen. Both Mn SOD induction and terminal differentiation, as reflected by human chorionic gonadotropin expression, were dependent on trophoblastic plating density. Increased levels of a smaller Mn SOD mRNA species correlated temporally with an increase in Mn SOD enzyme activity in cultured trophoblasts. These results demonstrate that Mn SOD gene expression and enzyme activity precede or are coordinately regulated with morphological and biochemical trophoblastic differentiation.
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PMID:Induction of manganese superoxide dismutase in cultured human trophoblast during in vitro differentiation. 172 88

K562 cells, a human erythroleukaemic cell line blocked for differentiation, commit towards erythrocytes when exposed to haemin (20 microM). The cells synthesize fetal haemoglobins and show site-specific binding of caeruloplasmin, a plasma copper protein. These events are set into motion by haemin. On the assumption that the binding of caeruloplasmin could reflect a greater need for copper, we sought to determine whether the transfer of 67Cu from caeruloplasmin was accelerated in haemin-induced compared with non-induced K562 cells. Cu,Zn superoxide dismutase (CuZnSOD) was the recipient. Haemin induction caused the K562 cells to lose CuZnSOD activity. By 96 h, the level of SOD activity was less than 60% of that of non-induced cells. The loss was confined entirely to the CuZn form, MnSOD activity staying essentially unchanged. Although CuZnSOD activity declined with the haemin induction, the incorporation of [4,5-3H]lysine into immunoprecipitable CuZnSOD protein was unaffected. There was also no change in CuZnSOD mRNA concentration in haemin-induced cells. Thus a loss of enzyme did not correlate with a decline in the synthesis de novo of CuZnSOD protein. When 48 h-induced cells were transferred to a medium supplemented with 0.2 microM-caeruloplasmin, CuZnSOD activity was restored to control levels in 24 h. Caeruloplasmin also stimulated the incorporation of [3H]lysine into immunoprecipitable CuZnSOD protein. Caeruloplasmin addition may have affected a post-translational regulatory site for CuZnSOD biosynthesis, possibly by providing copper for the newly synthesized enzyme.
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PMID:Regulation of Cu,Zn superoxide dismutase with copper. Caeruloplasmin maintains levels of functional enzyme activity during differentiation of K562 cells. 190 Apr 17

Pretreatment or "priming" with vincristine (VcR) has been documented to radioprotect animals from whole body irradiation by accelerating recovery of hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but the marked similarities between priming with VcR and with immune stimulants such as endotoxin and glucan have led to speculation that VcR may be inducing such radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The radioprotective ability of these cytokines, in turn, has been linked to an induction of the antioxidant enzyme manganese superoxide dismutase (Mn SOD). To establish whether priming with VcR is associated with induction of antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity. Furthermore, this increase occurs at the time VcR priming has been demonstrated previously to exhibit maximal radioprotection, suggesting that it may be contributing factor. However, VcR priming has been demonstrated to radioprotect both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD activity (or the other enzymes monitored) was found in the tumor-bearing group. Rather, the presence of tumor significantly suppressed antioxidant enzyme activity. Collectively, the present data suggest that it is unlikely that increased antioxidant enzyme activity is directly involved in the VcR priming response.
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PMID:Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice following vincristine treatment. 199 2

Superoxide dismutase is the main scavenger of superoxide radicals in the mammalian body. The liver has high levels of two types of superoxide dismutase enzymes, cytosolic Cu-Zn and mitochondrial Mn enzymes. The aim of the present study was to investigate the content of two distinct superoxide dismutases in liver during the perinatal transition from a hypoxic to a hyperoxic environment. Both isozymes were purified to homogeneity and used as immunogens in rabbits. Antisera raised were found to recognize only polypeptides of molecular weight 16,900 or 23,400, which correspond to Cu-Zn and Mn superoxide dismutases, respectively. It was found that the level of Cu-Zn superoxide dismutase enzymatic activity and protein as assessed by immunoquantitation increased 10-fold during the postnatal period, reaching adult levels by 3 weeks. In contrast, the amount of Mn superoxide dismutase content increased only twofold to adult levels during the first week of life. Neither of the superoxide dismutases showed an alteration in specific activity or apparent molecular weight in rat livers during ontogeny. These results show that the levels of two intracellular superoxide dismutases are differentially elevated during the perinatal period. It is suggested that each dismutase plays a different physiological role for superoxide scavenging in liver as a function of the hypoxic/hyperoxic environment at birth.
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PMID:Levels of Cu-Zn and Mn superoxide dismutases in rat liver during development. 200 4


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