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)

Only small amounts of superoxide dismutase (SOD) are present in the extracellular space to scavenge excess amounts of superoxide anions (02-) released after traumatic brain injury (TBI). Experiments were performed in rats with cerebral contusion produced by weight-drop technique. We investigated the effects of exogenous lecithinized SOD (PC-SOD) on accumulation of 02- produced in our model, by measuring the level of SOD activity (using the NBT-reducing method) and the expression of copper, zinc-SOD (Cu, Zn-SOD) mRNA (by Northern blot analysis). As determined by tissue-specific gravity, administration of PC-SOD reduced brain edema in the periphery of the lesion 6 h after contusion. SOD activity increased in the peripheral region at 30 min after contusion, but returned to normal levels at 6 h after TBI. Administration of PC-SOD increased SOD activity up to 6 h after TBI. The expression of Cu, Zn-SOD mRNA increased in the core region, peripheral portion, and contralateral hemisphere up to 6 h after TBI, then was suppressed in all three regions by PC-SOD. Our results confirm the important role of 02- in the development of brain edema after TBI and indicate that PC-SOD diminishes brain edema through a protective effect against 02-.
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PMID:Effects of lecithinized superoxide dismutase on traumatic brain injury in rats. 938 92

In order to investigate the radioresistance mechanism of human carcinoma cells, we measured intracellular manganese- (Mn-) and copper/zinc- (Cu/Zn-) superoxide dismutases (SODs), glutathione (GSH) and poly (ADP-ribose) polymerase (PARP) in radioresistant N10 and its parental KB cell lines. The Mn-SOD level was 1.3-fold less in N10 than in KB, but Mn-SOD was induced at 1.3 to 1.5-fold higher level in N10 than in KB by X-irradiation (4 Gy). Cu/Zn-SOD in N10 showed a higher level than that in KB both without and with irradiation. In addition, N10 had a 1.65-fold higher GSH level than did KB and became radiosensitive on treatment with buthionine sulfoximine, an inhibitor of GSH. Furthermore, PARP mRNA was highly expressed in N10 as compared to KB under unirradiated conditions. X-Irradiation reduced the PARP mRNA level in KB in a time-dependent manner, whereas the PARP mRNA level in N10 was still high at 6 h postirradiation. Assay for PARP activity demonstrated an approximately 3-fold higher activity in N10 than in KB under unirradiated conditions. X-Irradiation caused a rapid induction of PARP activity within 1 h in both cell lines, but treatment of cells with nicotinamide, a PARP inhibitor, markedly reduced the enzyme induction in N10, but not in KB, and potentiated the radiosensitivity in N10. These factors may all contribute to the radioresistance of the N10 cell line.
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PMID:Levels of superoxide dismutases, glutathione, and poly(ADP-ribose) polymerase in radioresistant human KB carcinoma cell line. 943 82

The effect of zinc (Zn) on cellular oxidative metabolism is complex and could be explained by multiple complementary interactions. In this study, we evaluated the impact of Zn on the pro-oxidant/antioxidant balance of HaCaT keratinocytes. Cells were submitted to a diffusible metal chelator able to induce intracellular Zn deprivation, TPEN, in combination or not with Zn chloride (ZnCl2), in the culture medium. The intracellular amount of Zn, copper (Cu), and iron (Fe) was determined, as well as CuZnSOD and MnSOD activities and glutathione reserves. The consequence of the modulation of Zn concentration on lipid peroxidation was also evaluated. TPEN induced a significant dose-dependent decrease in intracellular Zn and Cu (from 394-181 and 43-21 microg/g protein, respectively, after 6 h of TPEN 50 microM). No significant change in intracellular Fe concentration was found following TPEN exposure. The SOD activities were unchanged after 6 h of TPEN 50 microM application, either CuZnSOD or MnSOD. Cells exposure to TPEN induced a deep time- and dose-dependent decrease in their glutathione content (from 65-8 microM/g protein after 6 h of TPEN 50 microM), and a concomitant increase in glutathione in the cell-culture supernatants. No significant change in lipid peroxidation products was detected.
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PMID:Involvement of zinc in intracellular oxidant/antioxidant balance. 949 57

This study was undertaken to investigate the regulation of mitochondrial manganese superoxide dismutase (Mn-SOD) and cytosolic copper-zinc SOD (Cu,Zn-SOD) in the corpus luteum by inflammatory cytokines. We first examined the developmental expression of both SOD mRNAs in the rat corpus luteum throughout pregnancy. SOD mRNA levels were determined by semiquantitative reverse transcription-polymerase chain reaction. Whereas Cu,Zn-SOD mRNA levels decreased during late pregnancy, Mn-SOD mRNA levels remained elevated. We secondly examined the effects of inflammatory reaction on luteal SODs. Rats received injections of lipopolysaccharide (LPS; 5 mg, i.p.) on Day 15 of pregnancy, and corpora lutea were removed 2 h later. LPS caused an increase in Mn-SOD mRNA levels in the corpus luteum and a decrease in serum progesterone levels, but neither in levels of Cu,Zn-SOD mRNA. To further study the effects of LPS or LPS-induced cytokines, we incubated either whole corpora lutea obtained on Day 15 of pregnancy or a temperature-sensitive simian virus-40 transformed luteal cell line (GG-CL; derived from large luteal cells of the corpus luteum of pregnant rats) in serum-free medium with LPS, interleukin-1alpha (IL-1alpha), IL-beta, IL-6, and tumor necrosis factor alpha. LPS and these cytokines induced a remarkable increase in Mn-SOD mRNA levels in both corpora lutea and GG-CL cells but had no effect on Cu,Zn-SOD mRNA expression. In conclusion, Cu,Zn-SOD and Mn-SOD mRNAs are differently expressed and regulated in the corpus luteum of pregnancy. Mn-SOD mRNA, but not Cu,Zn-SOD mRNA, is highly induced by inflammatory cytokines and may play an important role in protecting luteal cells from inflammation-mediated oxidative damage.
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PMID:Differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase in the rat corpus luteum: induction of manganese superoxide dismutase messenger ribonucleic acid by inflammatory cytokines. 967 14

The function of the prion protein (PrPc) remains uncertain. It has been suggested that prion protein expression may aid cellular resistance to oxidative stress by influencing the activity of Cu/Zn superoxide dismutase (Cu,Zn SOD). The activity of Cu,Zn SOD was investigated in mice with different levels of PrPc expression. Increasing levels of PrPc expression were linked to increased levels of Cu,Zn SOD activity. Western-blot and Northern-blot analysis indicated that mice either lacking or overexpressing PrPc had levels of Cu,Zn SOD mRNA equivalent to those expressed in wild-type mice. Mice overexpressing the prion protein had lower levels of resistance to oxidative stress but higher expression levels of glutathione peroxidase, probably due to increased levels of hydrogen peroxide produced by increased Cu,Zn SOD activity. When cells were metabolically labelled with radioactive copper, increased radioactivity was immunoprecipitated with Cu,Zn SOD from mice with higher levels of PrPc. In addition, diethyldithiocarbamate, a copper chelator that inactivates Cu,Zn SOD by capturing copper from the molecule, is more able to inactivate Cu,Zn SOD expressed in animals with higher levels of PrPc. As recent studies have suggested that PrPc may regulate some aspect of copper metabolism, it is suggested that PrPc expression may regulate Cu,Zn SOD activity by influencing copper incorporation into the molecule.
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PMID:Prion protein expression and superoxide dismutase activity. 971 1

The corpus luteum expresses two enzymes that scavenge superoxide radicals and protect the cells from their toxic activities: cytosolic copper, zinc-superoxide dismutase (Cu,Zn-SOD) and mitochondrial manganese-SOD (Mn-SOD). The present study was undertaken to investigate whether the mRNA expression of each of these enzymes is regulated by luteotropic hormones. Cu,Zn-SOD and Mn-SOD mRNA levels were determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). We first examined the effects of prolactin (PRL) on Cu,Zn-SOD and Mn-SOD mRNA expression in the corpus luteum. Hypophysectomy of Day 3 pregnant rats caused a sharp decline in both Cu,Zn-SOD and Mn-SOD mRNA levels, which was completely reversed by PRL administration. To further examine the effects of PRL and rat placental lactogen (rPL) on the expression of these enzymes, either primary luteinized granulosa cells or temperature-sensitive simian virus-40 transformed luteal cells (GG-CL) were cultured with different doses of PRL or rPL. These hormones induced a remarkable increase in Cu,Zn-SOD and Mn-SOD mRNA levels in both primary luteinized granulosa cells and GG-CL cells. Interestingly, whereas PRL up-regulated the expression of the SOD in luteal cells, other luteotropic hormones such as estradiol and dexamethasone inhibited both SOD mRNA expression while progesterone had no effect. In conclusion, PRL and PRL-like hormones induce a protective ability against toxic oxygen radicals by stimulating the expression of SODs, a phenomenon that may play an important role in maintaining luteal cell integrity and steroidogenic capacity.
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PMID:Hormonal regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase messenger ribonucleic acid in the rat corpus luteum: induction by prolactin and placental lactogens. 971 59

The objectives of this study were to (1) determine whether transgenic (Tg) mice overexpressing copper/zinc-superoxide dismutase (CuZn-SOD) are protected from the deleterious effects of gut ischemia/reperfusion (I/R) and (2) compare the effectiveness of Tg SOD overexpression in attenuating I/R injury to intravascularly administered CuZn-SOD or manganese (Mn)-SOD. The accumulation of fluorescently labeled leukocytes and number of nonperfused sinusoids were monitored by intravital microscopy in livers of wild-type mice (C57BL/6), CuZn-SOD Tg mice, and wild-type mice receiving either CuZn-SOD or Mn-SOD. All parameters were measured for 1 hour after release of the occluded (for 15 minutes) superior mesenteric artery. Gut I/R in wild-type mice led to an increased number of stationary leukocytes, while reducing the number of perfused sinusoids (capillary no-reflow). All of these responses were significantly blunted in CuZn-SOD Tg mice, with a corresponding attenuation of liver enzyme release into plasma. Exogenously administered SOD had little or no effect on gut I/R-induced leukostasis or capillary no-reflow in the liver. These observations suggest a role for superoxide in gut I/R-induced leukostasis and hypoxic stress in the liver. Furthermore, the findings suggest that cellular localization of SOD activity is an important determinant of the protective actions of this enzyme in experimental models of I/R injury.
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PMID:Transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to hepatic leukostasis and capillary no-reflow after gut ischemia/reperfusion. 975 38

Reactive oxygen metabolites are implicated in the initiation and promotion of cancer. In addition, oxidant scavengers, such as manganese--(Mn-SOD) and copper/zinc--superoxide dismutase (Cu/Zn-SOD), are thought to contribute to colorectal cancer treatment response. In the present study, the prognostic significance of the Mn- and Cu/Zn-SOD antigen content of normal mucosa and carcinomas of 163 patients with colorectal cancer was evaluated in comparison with major clinicopathological parameters, with respect to the 5-year overall survival. The Mn-SOD content of carcinomas was found to be significantly higher than that of normal mucosa, whereas there was no difference in the Cu/Zn-SOD content between the normal mucosa and carcinomas. No association was demonstrable between the Mn-SOD and Cu/Zn-SOD content of the tissues and the assessed clinicopathological parameters (gender, age, localization, differentiation grade, diameter and Dukes' stage), with the exception of the Cu/Zn-SOD and the differentiation grade of the carcinomas. Univariate analysis showed that a high Mn-SOD content of carcinomas was associated with a poor 5-year overall survival of the patients with colorectal cancer. Multivariate analysis including all clinicopathological parameters revealed that this Mn-SOD parameter was prognostically independent. The Mn- and Cu/Zn-SOD content of normal mucosa and the Cu/Zn-SOD content of carcinomas were not associated with the overall survival of the patients. In conclusion, this study demonstrates that for patients with colorectal cancer the Mn-SOD content of colorectal carcinomas has a significant prognostic value that is independent from major clinicopathological parameters, including Dukes' stage.
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PMID:Superoxide dismutases in relation to the overall survival of colorectal cancer patients. 979 49

Air breathing, especially oxygen therapy, exposes the lung to reactive oxygen species (ROS). Antioxidant enzymes (AOEs) may protect the lung from ROS-mediated injury. Because expression of the key AOEs increases in several animal species during gestation, we investigated (1) the messenger RNA (mRNA) and activity levels of the key AOEs manganese and copper-zinc superoxide dismutases (MnSOD and CuZnSOD, respectively), catalase (CAT), and glutathione peroxidase (GPx) in adult lung samples and during ontogenesis; and (2) the difference in AOE expression between lung and liver. In the lung, the mRNA expression of MnSOD, CuZnSOD, and CAT increased toward adulthood, and GPx was unchanged. Pulmonary activities of MnSOD and CuZnSOD were unchanged, whereas CAT increased 3-fold from fetuses to adults. In the liver, the mRNA expression of MnSOD, CuZnSOD, and GPx increased, whereas that of CAT decreased toward adulthood. Hepatic activities of MnSOD and CuZnSOD increased 2-fold and 4-fold, respectively, whereas CAT was similar in fetuses and adults. Neonatal GPx activity was 2-fold higher in the lung and 6-fold higher in the liver compared with adults. The mRNA levels of MnSOD correlated positively with those of CuZnSOD and CAT in the lung, and GPx with those of MnSOD and CuZnSOD in the liver. Activities of MnSOD and CuZnSOD correlated positively in the liver. We conclude that the regulation of AOEs differs between human lung and liver, and is not tightly coordinated in either tissue.
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PMID:Expression and developmental profile of antioxidant enzymes in human lung and liver. 984 29

S-Nitrosothiols formed from the nitric oxide (NO)-dependent S-nitrosation of thiol-containing proteins and peptides such as albumin and glutathione (GSH) have been implicated in the transport, storage, and metabolism of NO in vivo. Recent data suggest that certain transition metals enhance the decomposition of S-nitrosothiols in vitro. The objective of this study was to determine what effect Cu, Zn superoxide dismutase (CuZn-SOD) has on the stability of certain S-nitrosothiols such as S-nitrosoglutathione (GSNO) in vitro. We found that CuZn-SOD (20 microM) but not Mn-SOD in the presence of GSH catalyzed the decomposition of GSNO with a Vmax of 6.7 +/- 0.4 microM/min and a Km of 5.6 +/- 0.5 microM at 37 degreesC. Increasing GSH concentrations with respect to CuZn-SOD resulted in complete decomposition of GSNO at concentrations of GSH:SOD of 2:1. Increasing GSH concentrations further from 0.1 to 10 mM resulted in a concentration-dependent attenuation in GSNO decomposition suggesting that SOD-catalyzed decomposition of GSNO would be maximal at concentrations of GSH known to be present in extracellular fluids (e.g., plasma). The decomposition of GSNO by CuZn-SOD resulted in the sustained production of NO. We propose that GSH reduces enzyme-associated Cu2+ to Cu1+ which mediates the reductive decomposition of the S-nitrosothiol to yield free NO. We conclude that CuZn-SOD may represent an important physiological modulator of steady-state concentrations of low-molecular-weight S-nitrosothiols in vivo.
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PMID:Effect of superoxide dismutase on the stability of S-nitrosothiols. 988 63


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