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 dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2. However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.
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PMID:Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure. 963 37

Superoxide dismutase (SOD) is considered to be the first line of defense against oxygen toxicity. It exists as a family of three metalloproteins with copper,zinc (Cu,ZnSOD), manganese (MnSOD), and iron (FeSOD) forms. In this work, we have targeted Escherichia coli FeSOD to the mitochondrial intermembrane space (IMS) of yeast cells deficient in mitochondrial MnSOD. Our results show that FeSOD in the IMS increases the growth rate of the cells growing in minimal medium in air but does not protect the MnSOD-deficient yeast cells when exposed to induced oxidative stress. Cloned FeSOD must be targeted to the mitochondrial matrix to protect the cells from both physiological and induced oxidative stress. This confirms that the superoxide radical is mainly generated on the matrix side of the inner mitochondrial membrane of yeast cells, without excluding its potential appearance in the mitochondrial IMS where its elimination by SOD is beneficial to the cells.
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PMID:Cloned prokaryotic iron superoxide dismutase protects yeast cells against oxidative stress depending on mitochondrial location. 1006 23

The present study was designed to investigate the role of manganese (Mn) as an antioxidant element. In vitro experiments have been conducted to evaluate the ability of Mn in scavenging oxygen free radicals. Superoxide (O*-) and hydroxyl (OH*-) radicals were generated in vitro by using xanthine and xanthine oxidase system and fenton reactions respectively. Different concentrations of Mn (II) and Mn (III) were used in the reaction mixture to evaluate free radical scavenging ability of Mn. The results indicated that Mn scavenged superoxide radicals at nanomolar concentrations whereas hydroxyl radicals were scavenged at micromolar concentrations. In addition, Mn-superoxide dismutase (SOD) activity was measured in different regions of brain in adult male rats treated with MnCl2. The results showed that Mn-SOD activity increased in Mn treated animals. Therefore, the data support the hypothesis that Mn is one of the essential elements which can protect against oxidative damage, however, at higher concentrations Mn can be neurotoxic by generating the free radicals.
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PMID:Manganese scavenges superoxide and hydroxyl radicals: an in vitro study in rats. 1008 17

When life first evolved on Earth, there was little oxygen in the atmosphere. Evolution of antioxidant defences must have been closely associated with the evolution of photosynthesis and of O2-dependent electron transport mechanisms. Studies with mice lacking antioxidant defences confirm the important roles of MnSOD and transferrin in maintaining health, but show that glutathione peroxidase (GPX) and CuZnSOD are not essential for everyday life (at least in mice). Superoxide can be cytotoxic by several mechanisms: one is the formation of hydroxyl radicals. There is good evidence that OH* formation occurs in vivo. Other important antioxidants may include thioredoxin, and selenoproteins other than GPX. Nitric oxide may be an important antioxidant in the vascular system. Diet-derived antioxidants are important in maintaining human health, but recent studies employing "biomarkers" of oxidative DNA damage are questioning the "antioxidant" roles of beta-carotene and ascorbate. An important area of future research will be elucidation of the reasons why levels of steady-state oxidative damage to DNA and lipids vary so much between individuals, and their predictive value for the later development of human disease.
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PMID:Antioxidant defence mechanisms: from the beginning to the end (of the beginning). 1051 32

It is important to know responses of the pathogenic fungi to reactive oxygen species by which hosts protect themselves against fungal infection. In the present study, sensitivities to the superoxide radical (O2-) and superoxide dismutase (SOD) were compared between a wild-type parent strain and a respiration-deficient mutant of Candida albicans. When their survival was examined on an agar medium containing an intracellular O2- generator, paraquat (PQ), the parent strain was selectively killed by increasing the PQ concentration. In contrast, when cells of both strains were illuminated in a riboflavin solution, they exhibited similar sensitivity to O2- generated extracellularly by photo-reduced riboflavin. There were no large differences in sensitivity to hydrogen peroxide in the two strains. Thus, the high tolerance of the mutant to PQ was suggested to result from low intracellular O2- generation by PQ due to the respiratory deficiency. It is generally accepted that fungal cells contain manganese (Mn)-SOD in the mitochondria and copper and zinc (CuZn)-SOD in the cytoplasm. Cyanide-insensitive SOD activity (attributable to Mn-SOD) was dominant in the parent strain throughout growth phases, whereas cyanide-sensitive activity (attributable to CuZn-SOD) occurred in the mutant. The activity bands of Mn- and CuZn-SODs were clearly separated by electrophoresis of the cell extracts of both strains on non-denaturing polyacrylamide gels. The electrophoretic profiles obtained were consistent with the results of the activity assay. These results showed that the respiratory deficiency affected oxidative stress sensitivity and SOD in C. albicans.
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PMID:Oxidative stress sensitivity and superoxide dismutase of a wild-type parent strain and a respiratory mutant of Candida albicans. 1052 Jan 55

To study the possible role of the superoxide radical and its scavenging system in the decidua of early pregnancy, superoxide dismutase (SOD) values and concentrations of lipid peroxide and prostaglandin F(2alpha) (PGF(2alpha)) were analysed in the decidua obtained from normal pregnancy and failed pregnancy. Failed pregnancy was divided into two groups; spontaneous abortion with or without vaginal bleeding. In the spontaneous abortion with vaginal bleeding, total SOD activities, Cu,Zn-SOD activities and Cu,Zn-SOD mRNA values in the decidua were significantly lower, and concentrations of lipid peroxide and PGF(2alpha) were significantly higher, than those in the normal pregnancy and the spontaneous abortion without vaginal bleeding. In contrast, activities and mRNA values of Mn-SOD were significantly higher in the spontaneous abortion with vaginal bleeding than the other two groups. There was no significant difference in all of these parameters between the normal pregnancy and the spontaneous abortion without vaginal bleeding. In conclusion, the decrease in Cu,Zn-SOD expression and the increase in lipid peroxide in the decidua could be involved in the termination of spontaneous abortion, mediated through the increase in PGF(2alpha) synthesis. In other words, Cu,Zn-SOD may contribute to the maintenance of pregnancy by preventing the accumulation of superoxide radicals that cause PGF(2alpha) synthesis.
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PMID:Decreased superoxide dismutase expression and increased concentrations of lipid peroxide and prostaglandin F(2alpha) in the decidua of failed pregnancy. 1087 52

Superoxide (O2-) has been implicated in the pathogenesis of pulmonary O2 toxicity. The studies using transgenic and knockout mice of each of the three isoforms of superoxide dismutase (SOD) e.g. , CuZnSOD, MnSOD and extracellular SOD (EC-SOD), have demonstrated that O2- produced in the mitochondria from its electron transport system and extracellular O2- generated by infiltrating neutrophils, and possibly its derivatives e.g., hydroxyl radical and peroxynitrite, are important mediators of hyperoxia-induced pulmonary injury, while cytoplasmic O2- plays a limited, if any, role in the pathogenesis of pulmonary O2 toxicity. Distal airway epithelial cells including type II alveolar and non-ciliated bronchiolar epithelial cells, are important targets for O2 radicals under the hyperoxic condition. The accessibility of these distal airway epithelial cells to in vivo gene transfer through the tracheal route of administration, suggests the potential for in vivo transfer of MnSOD and EC-SOD genes as a future approach in the prevention of pulmonary O2 toxicity.
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PMID:Superoxide dismutase and pulmonary oxygen toxicity: lessons from transgenic and knockout mice (Review). 1111 2

Cyclooxygenase-2 (COX-2) is an essential enzyme for prostaglandin synthesis from arachidonic acid, during which considerable amounts of superoxide are produced. During pathological conditions, superoxide and nitric oxide (NO) rapidly form peroxynitrite, a potent cytotoxin, causing symptoms referred to as oxidative stress response. Superoxide is controlled by enzymes such as manganese- or copper-zinc-dependent superoxide dismutase (Mn-SOD, CuZn-SOD), glutathione peroxidase (GPx) and antioxidants derived from heme oxygenase (HO) activity such as biliverdin and bilirubin. NO derives from 3 NO-synthases (NOS I-III) from which the calcium-dependent NOS-I and III are activated rapidly due to hyperexcitation. We studied the induction of COX-2 by immunohistochemistry at days 1, 2 and 5 following cortical photothrombosis in normal and MK-801 treated rats. The results showed a weak constitutive, neuronal expression of COX-2 in cortex and amygdala. Layers II+III contained considerably more COX-2 than infragranular layers. One and 2 days following injury COX-2 was highly upregulated in the supragranular layers of the whole injured hemisphere compared with sham-operated animals and compared to the contralateral unlesioned hemisphere, whereas at day 5 COX-2 levels had returned to baseline. MK-801 treatment caused a reduction in COX-2 upregulation at day one and by day 2 no significant differences between injured and contralateral hemisphere were measurable. COX-2 positive neurons were found in close association with NOS-I containing neurons and their fibers but were not colocalized. In addition, codistribution of COX-2 was found with HO-1, CuZn-SOD and GPx containing cells, whereas COX-2 was colocalized with HO-2 and/or MnSOD in cortical neurons.
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PMID:Unilateral upregulation of cyclooxygenase-2 following cerebral, cortical photothrombosis in the rat: suppression by MK-801 and co-distribution with enzymes involved in the oxidative stress cascade. 1111 8

Superoxide dismutases (SODs) are involved in the protection of cells from oxygen toxicity. However, several papers have reported that the overexpression of CuZn-SOD causes oxidative damage to cells. We investigated a mechanism by which an excess of SODs accelerates oxidative stress. The presence of CuZn-SOD, Mn-SOD or Mn(II) enhanced the frequency of DNA damage induced by hydrogen peroxide (H2O2) and Cu(II), and altered the site specificity of the latter: H2O2 induced Cu(II)-dependent DNA damage with high frequency at the 5'-guanine of poly G sequences; when SODs were added, the frequency of cleavages at thymine and cytosine residues increased. SODs also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by H2O2 and Cu(II). We conclude that SODs may increase carcinogenic risks, e.g. of tumors in Down syndrome.
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PMID:Superoxide dismutases enhance H2O2-induced DNA damage and alter its site specificity. 1133 89

Spodoptera frugiperda Sf-9 (Sf-9) and Trichoplusia ni BTI-Tn-5B1-4 (Tn-5B1-4) insect cell lines were found to contain unique assemblages of antioxidant enzymes. Specifically, the Sf-9 insect cell line contained Manganese and Copper-Zinc superoxide dismutase (MnSOD and CuZnSOD) for reducing the superoxide radical (O(2)(*-)) to hydrogen peroxide (H(2)O(2)) and ascorbate peroxidase (APOX) for reducing the resulting H(2)O(2) to H(2)O. Approximately one third of the total SOD activity was found to be MnSOD. The Tn-5B1-4 cells were also found to contain MnSOD (approximately two thirds of the total SOD activity), CuZnSOD and APOX activities. However, the Tn-5B1-4 cell line, in contrast to the Sf-9 cell line, contained catalase (CAT) activity for reducing H(2)O(2) to H(2)O. Both the Sf-9 and Tn-5B1-4 cell lines contained glutathione reductase and dehydroascorbic acid reductase activities for regenerating the reduced forms of glutathione and ascorbic acid, respectively. In addition, both cell lines contained glutathione S-transferase peroxidase activity towards hydroperoxides other than H(2)O(2). Finally, neither cell line contains the glutathione peroxidase activity that is ubiquitous in mammalian cells.
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PMID:Antioxidant defense systems of two lipidopteran insect cell lines. 1136 23


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