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 (SODs) are vital components that defend against oxidative stress through decomposition of superoxide radical. Escherichia coli contains two highly homologous SODs, a manganese- and an iron-containing enzyme (Mn-SOD and Fe-SOD, respectively). In contrast, a single Mn-SOD is present in Bacillus subtilis. In E. coli, the absence of SODs was found to be associated with an increased sensitivity to cadmium, nickel and cobalt ions. Mutants lacking either sodA or sodB exhibited metal resistance to levels comparable to that of the wild-type strain. Although sod-deficient mutant cells were more resistant to zinc than their wild-type counterpart, no differences between the strains were observed in the presence of copper. In B. subtilis, the sodA mutation had no effect on cadmium and copper resistance. These results suggest that intracellular generation of superoxide by cadmium, nickel and cobalt is toxic in E. coli. They support the participation of sod genes in its protection against metal stress.
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PMID:The manganese and iron superoxide dismutases protect Escherichia coli from heavy metal toxicity. 1176 65

Superoxide dismutases are an ubiquitous family of enzymes that function to efficiently catalyze the dismutation of superoxide anions. Three unique and highly compartmentalized mammalian superoxide dismutases have been biochemically and molecularly characterized to date. SOD1, or CuZn-SOD (EC 1.15.1.1), was the first enzyme to be characterized and is a copper and zinc-containing homodimer that is found almost exclusively in intracellular cytoplasmic spaces. SOD2, or Mn-SOD (EC 1.15.1.1), exists as a tetramer and is initially synthesized containing a leader peptide, which targets this manganese-containing enzyme exclusively to the mitochondrial spaces. SOD3, or EC-SOD (EC 1.15.1.1), is the most recently characterized SOD, exists as a copper and zinc-containing tetramer, and is synthesized containing a signal peptide that directs this enzyme exclusively to extracellular spaces. What role(s) these SODs play in both normal and disease states is only slowly beginning to be understood. A molecular understanding of each of these genes has proven useful toward the deciphering of their biological roles. For example, a variety of single amino acid mutations in SOD1 have been linked to familial amyotrophic lateral sclerosis. Knocking out the SOD2 gene in mice results in a lethal cardiomyopathy. A single amino acid mutation in human SOD3 is associated with 10 to 30-fold increases in serum SOD3 levels. As more information is obtained, further insights will be gained.
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PMID:Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. 1212 55

Spinocerebellar ataxia 1 (SCA1) is an inherited neurodegenerative disorder caused by expansion of the polyglutamine stretch in ataxin-1, the SCA1 gene product. Polyglutamine expansion leads to the aggregation of ataxin-1 proteins. Superoxide dismutases (SODs) are involved in the pathogenesis of other aggregate-forming neurodegenerative diseases and are known to localize in the cytoplasm. Here, we show that Cu/Zn-SOD is translocated into the nucleus of HeLa cells in the presence of expanded ataxin-1, whereas Mn-SOD is localized in the cytoplasm: the longer the expansion of polyglutamine, the higher the level of translocation of Cu/Zn-SOD. In addition, the oxidation of intracellular proteins occurs with higher frequency in the presence of mutant ataxin-1 (82Q), suggesting that the functional activity of Cu/Zn-SOD might be decreased by mutant ataxin-1. We demonstrate that mutant ataxin-1-expressing cells encounter mitochondrial dysfunction in the conditions of oxidative stress. Our results suggest that polyglutamine-expanded ataxin-1 increases the levels of reactive oxygen species in HeLa cells.
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PMID:Polyglutamine-expanded ataxin-1 recruits Cu/Zn-superoxide dismutase into the nucleus of HeLa cells. 1289 74

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH(*)) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H(2)O(2) is hampered in these cells, thereby increasing not only the risk of detrimental effects of H(2)O(2) directly, but also those of its extremely reactive derivatives such as OH(*). Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes.
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PMID:Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease. 1295 13

Mitochondria are the major site for the generation of ATP at the expense of molecular oxygen. Significant fractions (approximately 2%) of oxygen are converted to the superoxide radical and its reactive metabolites (ROS) in and around mitochondria. Although ROS have been known to impair a wide variety of biological molecules including lipids, proteins and DNA, thereby causing various diseases, they also play critical roles in the maintenance of aerobic life. Because mitochondria are the major site of free radical generation, they are highly enriched with antioxidants including GSH and enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase, on both sides of their membranes to minimize oxidative stress in and around this organelle. The present work reviews the sites and mechanism of ROS generation by mitochondria, mitochondrial localization of Mn-SOD and Cu,Zn-SOD which has been postulated for a long time to be a cytosolic enzyme. The present work also describes that a cross-talk of molecular oxygen, nitric oxide (NO) and superoxide radicals regulates the circulation, energy metabolism, apoptosis, and functions as a major defense system against pathogens. Pathophysiological significance of ROS generation by mitochondria in the etiology of aging, cancer and degenerative neuronal diseases is also described.
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PMID:Mitochondrial generation of reactive oxygen species and its role in aerobic life. 1452 65

Superoxide dismutases (SOD) convert superoxide radicals into less damaging hydrogen peroxide. The opportunistic human pathogen Candida albicans is known to express CuZnSOD (SOD1) and MnSOD (SOD3) in the cytosol and MnSOD (SOD2) in the mitochondria. We identified three additional CuZn-containing superoxide dismutases, SOD4, SOD5, and SOD6, within the sequence of the C. albicans genome. The transcription of SOD5 was up-regulated during the yeast to hyphal transition of C. albicans, and SOD5 was induced when C. albicans cells were challenged with osmotic or with oxidative stresses. SOD5 transcription was also increased when cells were grown on nonfermentable substrates as the only carbon source. The Rim101p transcription factor was required for all inductions observed, whereas the Efg1p transcription factor was specifically needed for serum-modulated expression. Deletion of SOD5 produced a viable mutant strain that showed sensitivity to hydrogen peroxide when cells were grown in nutrient-limited conditions. Sod5p was found to be necessary for the virulence of C. albicans in a mouse model of infection. However, the sod5 mutant strain showed the same resistance to macrophage attack as its parental strain, suggesting that the loss of virulence in not due to an increased sensitivity to macrophage attack.
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PMID:Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene. 1461 19

We hypothesized that aging is characterized by a reduced release of nitric oxide (NO) in response to shear stress in resistance vessels. Mesenteric arterioles and arteries of young (6 mo) and aged (24 mo) male Fischer 344 rats were isolated and cannulated. Shear stress (15 dyn/cm(2))-induced dilation was significantly reduced and shear stress (1, 5, 10, and 15 dyn/cm(2))-induced increases in perfusate nitrite were significantly smaller at all shear stress levels in vessels of aged rats. Inhibition of NO synthesis abolished shear stress-induced release of nitrite. Furthermore, shear stress (15 dyn/cm(2))-induced release of nitrate was significantly higher and total nitrite (nitrite plus nitrate) was significantly lower in vessels of aged rats. Tiron or SOD significantly increased nitrite released from vessels of aged rats, but this was still significantly less than that in young rats. Superoxide production was increased and the activity of SOD was decreased in vessels of aged rats. There were no differences in endothelial NO synthase (eNOS) protein and basal activity or in Cu/Zn-SOD and Mn-SOD proteins in vessels of the two groups, but extracellular SOD was significantly reduced in vessels of aged rats. Maximal release of NO induced by shear stress plus ACh (10(-5) M) was comparable in the two groups, but phospho-eNOS in response to shear stress (15 dyn/cm(2)) was significantly reduced in vessels of aged rats. These data suggest that an increased production of superoxide, a reduced activity of SOD, and an impaired shear stress-induced activation of eNOS are the causes of the decreased shear stress-induced release of NO in vessels of aged rats.
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PMID:Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. 1475 61

Superoxide dismutases (SODs) are metalloenzymes that protect aerobic organisms from oxidative damage mediated by the superoxide radical. While the Fe- and Mn-dependent SODs from E. coli possess virtually identical protein folds and active-site geometries, they are strictly metal specific. To explore the origin of this extraordinary metal-ion specificity and to elucidate the mechanisms by which these enzymes tune the geometric and electronic properties, and thus the reactivity, of their active-site metal ions, we utilized a combination of spectroscopic and computational methods to study the native enzymes, their metal-substituted derivatives, and several mutant proteins. Results from our research described in this Account reveal that second-sphere residues are critically involved in controlling both thermodynamic and kinetic properties of the Fe- and MnSOD active sites.
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PMID:Combined spectroscopic/computational studies on Fe- and Mn-dependent superoxide dismutases: insights into second-sphere tuning of active site properties. 1526 May 8

The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide radical production in the rat brain was examined after injection of kainate, non-NMDA receptor agonist, kainate plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), selective AMPA/kainate receptor antagonist, or kainate plus 2-amino-5-phosphonopentanoic acid (APV), selective NMDA receptor antagonist. Competitive glutamate receptor antagonists were injected with kainate unilaterally into the CA3 region of the rat hippocampus. We investigated superoxide production and mitochondrial MnSOD activity after injection. The measurements took place at different times (5, 15 min, 2, 48 h and 7 days) in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. Used glutamate antagonists APV and CNQX both expressed sufficient neuroprotection in sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. Following intrahippocampal antagonists injection they, also, interpose different neuroprotection effect on the induction of MnSOD activity in distinct brain regions affected by the injury, which are functionally connected via afferents and efferents. It suggests that MnSOD protects the cells in these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.
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PMID:Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection. 1527 61

Superoxide dismutases (SODs) are believed to play a crucial role in protecting cells against oxygen toxicity. There are three forms of SOD: cytosolic Cu-Zn SOD, mitochondrial Mn SOD, and extracellular SOD (EC SOD). Extracellular SOD is primarily a tissue enzyme, but the role of EC SOD in skin is unclear. Therefore, this study investigated the distribution of EC SOD in the skin using immunohistochemistry and examining the patterns of EC SOD gene expression following ultraviolet (UV) irradiation in comparison with those of Cu-Zn SOD and Mn SOD in mouse dorsal skin using Northern blot analysis. Immunohistochemical analysis showed that EC SOD was abundantly located in the epidermis as well as in the dermis, but the gene expression of EC SOD mRNA was more abundant in the dermis than in the epidermis. The gene expression levels of all three types of SODs after UV irradiation were induced differently according to the type and UV irradiation dose. The EC SOD mRNA expression level was increased relatively later than that of Cu-Zn SOD and Mn SOD. The EC SOD mRNA level was significantly higher at 6 h and 48 h after UVA irradiation and psoralen plus ultraviolet-A treatment, respectively. Ultraviolet-B irradiation increased the EC SOD mRNA expression level, with maximum at 48 h. These suggest that EC SOD participates in the majority of antioxidant systems in the skin, and it may have different defensive roles from Cu-Zn SOD and Mn SOD against UV-induced injury of the skin.
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PMID:Extracellular superoxide dismutase tissue distribution and the patterns of superoxide dismutase mRNA expression following ultraviolet irradiation on mouse skin. 1550 Jun 41


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