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)

IL-1 and TNF are important mediators in the inflammatory response, and have been associated with endothelial cell damage in the lung. TNF and IL-1 cell-mediated injury has been proposed to occur through an increase in intracellular oxygen free radical production. However, these cytokines have also been shown to protect the lung from hyperoxia-mediated oxidant injury. In this paper we evaluated the response of the antioxidant enzymes, MnSOD and Cu/ZnSOD to IL-1, TNF, and LPS in both rat pulmonary artery and microvascular endothelial cells. These mediators produced an increase in MnSOD but not Cu/ZnSOD expression in both rat pulmonary endothelial cells. An additive effect was observed with co-treatment by the cytokines with LPS. The MnSOD mRNA induction is dependent upon a transcriptional event, but did not require de novo protein synthesis.
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PMID:Regulation of manganese superoxide dismutase: IL-1 and TNF induction in pulmonary artery and microvascular endothelial cells. 138 89

To test directly whether mitochondrial Mn-superoxide dismutase (Mn-SOD) protects the lung epithelium from oxygen-induced injury, transgenic mice were produced in which the expression of human Mn-SOD mRNA was directly by transcriptional elements from the human pulmonary surfactant protein C gene. Human Mn-SOD mRNA was expressed in a lung-specific manner, and increased Mn-SOD protein was detected within mitochondria of alveolar Type II and nonciliated bronchiolar cells of the distal respiratory epithelium of the transgenic mice. The activity of Mn-SOD, but not catalase, CuZn-SOD, or glutathione peroxidase, was increased in lungs of transgenic mice. Transgenic mice were highly protected from lung injury during exposure to 95% oxygen, surviving significantly longer than nontransgenic littermates. Pulmonary pathology demonstrated decreased hemorrhage, hyaline membrane formation, and alveolar and interstitial edema in transgenic animals. The finding that increased Mn-SOD in distal respiratory epithelial cells confers protection from oxygen injury provides a basis for novel therapies to protect lung from injury during oxygen therapy of acute and chronic lung diseases.
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PMID:Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury. 138 28

Hypoxic injury of rat astroglial cells in primary culture initiates several modifications of their functional integrity. A significant decrease of the cellular oxygen consumption was observed in astrocytes submitted to a 15 h low oxygen pressure. The addition of almitrine (dialylamino-4',6'-triazinyl 2')-1-(bis-parafluorobenzydryl)-4-piperazine, a chemoreceptor agonist, restored almost completely the respiratory activity of the hypoxia treated cells. In order to test the hypothesis that oxygen free radical formation may contribute to the cellular damage resulting from ischemia, the activities of the following antioxidant enzymatic systems have been determined in the cultured astrocytes: Cu,Zn- and Mn-superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione reductase (GSH-RED), and catalase (CAT). Only a significant and specific decrease of the Mn-SOD activity was observed after the hypoxia-normoxia exposure. The other oxygen radical scavenging systems were not modified. The addition of almitrine antagonized the decrease of the Mn-SOD activity observed in the low oxygen pressure treated cells, but results clearly point-out the importance of oxygen radical production in the astroglial response after hypoxic injury. A beneficial effect of almitrine toward the observed alteration has been underlined. It is suggested that some mitochondrial alterations could be related to some aspects of the astroglial hypoxic stress.
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PMID:Free radical scavenging systems of rat astroglial cells in primary culture: effects of anoxia and drug treatment. 140 63

We investigated the developmental profile of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in tissue sections obtained from fetal (Day 12 to 21 of gestation) and neonatal (Day 0 and 6) rats. Tissues were stained immunohistochemically with specific antisera against the respective rat SODs. There was a general trend towards richness of SODs in the epithelial linings and metabolically active sites, although differential distribution between the two SODs also existed. At Day 12 of gestation, immunoreactivity for both SODs was detected in the cardiomyocytes but not in other tissues. Hepatocytes expressed CuZnSOD at Day 14 and MnSOD at Day 17. By Day 18 CuZnSOD was detected in the epithelial cells of the gastrointestinal tract, respiratory tract, pancreatic islets, kidneys, and adrenals. These tissues exhibited MnSOD staining at Day 19. CuZnSOD occurred in the epithelia of the thyroid, thymus, and salivary glands at Day 19, while MnSOD was seen at Day 21. The increase in intensity of the staining for SODs occurred no later than postnatal Day 0, indicating that most tissues accumulated SODs during late gestation. Breathing atmospheric oxygen during early extrauterine life did not appreciably intensify the SOD staining. These results suggest that perinatal increase in SODs occurs as a general mechanism of preparation for birth.
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PMID:Immunohistochemical localization of superoxide dismutases in fetal and neonatal rat tissues. 143 Oct 59

Recent studies have demonstrated that intracolonic administration of trinitrobenzenesulfonic acid (TNB) dissolved in ethanol produces chronic colitis in rats, and that this model shares many features of human inflammatory bowel disease (IBD), particularly Crohn's disease. We investigated the role of free radicals in the pathogenesis of this colitis model. In the early stage of this colitis, antioxidant enzymes (such as superoxide dismutase, glutathione peroxidase) and an antioxidant, alpha-tocopherol, were significantly decreased with the severity of colonic damage. Mn-SOD at a dose of 50000 U/kg attenuated this colitis when preadministered subcutaneously one hour before the induction of colitis. These results suggest that oxygen-derived free radicals may play an important role in this colitis.
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PMID:Possible role of free radicals in the chronic inflammation of the gut. 145 May 97

Evidence is reported that liver manganese deficiency, whether artificially produced by the administration of a Mn-deficient diet, or physiologically occurring in the neonatal life, in mice and rats respectively, causes the down-regulation of the manganese-containing superoxide dismutase at (pre)-transcriptional level. These observations, in addition to previous data concerning Mn-deficiency and the low level of expression of MnSOD in Morris hepatomas, strongly support the role played by the metal ion in the control of the MnSOD by a mechanism of gene activation. While the molecular events taking place in such regulation are not yet identified, the involvement of reactive oxygen species (ROS) as second messengers in the activation of specific transcription factors is suggested.
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PMID:Transcriptional regulation of MnSOD by manganese in the liver of manganese-deficient mice and during rat development. 148 98

Superoxide dismutases (SOD) are ubiquitous in aerobic organisms and are believed to play a significant role in protecting cells against the toxic, often lethal, effect of oxygen free radicals. However, direct evidence that SOD does in fact participate in such a protective role is scant. The MnSOD-deficient yeast strain (Sod2d) offered an opportunity to test the functional role of one of several SOD isozymes from the higher plant maize in hopes of establishing a functional bioassay for other SODs. Herein, we present evidence that MnSOD functions to protect cells from oxidative stress and that this function is conserved between species. The maize Sod3 gene was introduced into the yeast strain Sod2d where it was properly expressed and its product processed into the yeast mitochondrial matrix and assembled into the functional homotetramer. Most significantly, expression of the maize Sod3 transgene in yeast rendered the transformed yeast cells resistant to paraquat-induced oxidative stress by complementing the MnSOD deficiency. Furthermore, analyses with various deletion mutants of the maize SOD-3 transit peptide in the MnSOD-deficient yeast strain indicate that the initial portion (about 8 amino acids) of the maize transit peptide is required to direct the protein into the yeast mitochondrial matrix in vivo to function properly. These findings indicate that the functional role of maize MnSOD is conserved and dependent on its proper subcellular location in the mitochondria of a heterologous system.
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PMID:Expression of the maize MnSod (Sod3) gene in MnSOD-deficient yeast rescues the mutant yeast under oxidative stress. 151 16

Null mutants of superoxide dismutase (SOD) in Saccharomyces cerevisiae are associated with a number of biochemical defects. In addition to being hypersensitive to oxygen toxicity, strains containing deletions in both the SOD1 (encoding Cu/Zn-SOD) and SOD2 (encoding Mn-SOD) genes are defective in sporulation, are associated with a high mutation rate, and are unable to biosynthesize lysine and methionine. The sod-linked defect in lysine metabolism was explored in detail and was found to occur at an early step in lysine biosynthesis, evidently at the level of the alpha-amino adipate transaminase. To better understand the role of SOD in cell metabolism, our laboratory has isolated yeast suppressors that have bypassed the SOD defect ("bsd" strains), that is, S. cerevisiae cells lacking SOD, yet resistant to oxygen toxicity. Two nuclear bsd complementation groups have been identified, and both suppress a variety of biological defects associated with sod1 and sod2 null mutants. These results demonstrate that a single gene mutation can alleviate the requirement for SOD in cell growth. Both bsd complementation groups are unable to utilize many non-fermentable carbon sources, suggesting a possible suppressor-linked defect in electron transport.
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PMID:Yeast lacking superoxide dismutase. Isolation of genetic suppressors. 152 70

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.
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PMID:5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats. 153 18

We studied the effect of Cu,Zn-superoxide dismutase (SOD) and Mn-SOD, which are specific scavenging enzymes of the superoxide anion radical, on ovulation and examined the localization of SOD in rat ovaries. The results were as follows. 1) The number of ova in the Cu,Zn-SOD (8 mg x 4) administrated group (27.8 +/- 5.4 : p less than 0.01) was significantly reduced compared to the control group (49.0 +/- 3.3). Similarly, the number of ova in the Mn-SOD (2 mg x 2) administrated group (16.9 +/- 7.6 : p less than 0.01) was significantly reduced compared to the control (52.9 +/- 6.3). 2) In the rat ovary, Cu,Zn-SOD examined by the immunohistological method was found to be localized in the granulosa cells of mature Graafian follicles, growing follicles, primordial follicles and epithelial cells of the fallopian tubes. Mn-SOD was localized in the external theca cells of mature Graafian follicles and the corpus luteum. The activity of SOD estimated by the modified nitroblue tetrazolium method was consistent with the immunohistological localization of both SODs. We considered that oxygen radicals and SODs play an important role in rat ovulation, and Cu,ZN-SOD and Mn-SOD have a different localization and action in the rat ovary.
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PMID:[Role of oxygen radical and superoxide dismutase in ovulation in the rat]. 154 52


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