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)

The alterations of superoxide dismutase iso-enzyme (Cu,Zn-SOD and Mn-SOD) activities, contents, and mRNA expressions with aging were studied in rat soleus muscle (SO) and extensor digitorum longus muscle (EDL). The activity and content of Cu,Zn-SOD in both muscles were significantly higher in old rats (24 months old) than in young rats (4 months old), whereas those of Mn-SOD showed no difference between young and old rats. After normalization to citrate synthase (CS) activity, however Mn-SOD/CS ratio in SO also showed the age-related increase. Moreover, the activities of other major antioxidant enzymes, glutathione peroxidase (GPX) and catalase (CAT), indicated age-related increases only in SO. As for the expressions of mRNAs for SOD iso-enzymes, that of Cu,Zn-SOD in either muscle showed no significant change with aging, unlike its activity and content, although that of Mn-SOD was decreased with aging only in EDL. Thus, aging appeared to raise the level of antioxidant enzyme system in rat skeletal muscle. However, the resistance of Cu,Zn-SOD and Mn-SOD to oxidative stress accompanied by aging was different, the former being obviously greater than the latter. Such changes also differed in muscle fiber type suggesting that fast-twitch fibers are more susceptible to age-related oxidative stress than slow-twitch fibers.
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PMID:Alterations of superoxide dismutase iso-enzyme activity, content, and mRNA expression with aging in rat skeletal muscle. 871 78

Antioxidant enzyme activities in fibroblasts and erythrocytes prepared from normal and psoriatic patients were measured and compared. The most significant differences were noted in superoxide dismutase (SOD) activities. A dramatic (5.2-fold) increase in Mn-SOD activity along with a lesser (1.8-fold) increase in CuZn-SOD activity was observed in fibroblasts from lesional and nonlesional psoriatic skin. The increase of Mn-SOD activity was correlated with an increase of both protein and mRNA. A slight (1.2-fold) increase in CuZn-SOD activity was also found in psoriatic as compared to normal red blood cells, while Mn-SOD activity was not present in these cells. In contrast, both glutathione peroxidase and catalase activities were only slightly (1.3-fold) increased in psoriatic fibroblasts, with no appreciable change noted in psoriatic erythrocytes. Likewise, glutathione levels were observed to be similar in normal and psoriatic cells. The increases in SOD activities did not appear to correlate with the severity of the disease as expressed by the Psoriatic Area Severity Index score or with plasma inflammatory markers. These results demonstrate that antioxidant enzyme activities, particularly Mn-SOD in fibroblasts and CuZn-SOD in erythrocytes, are significantly elevated in cells from psoriatic patients.
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PMID:Antioxidant enzymes in psoriatic fibroblasts and erythrocytes. 875 78

Maternal diabetes during pregnancy is associated with an increased rate of congenital malformations in the offspring. The exact molecular etiology of the disturbed embryogenesis is unknown, but an involvement of radical oxygen species in the teratological process has been suggested. Oxidative damage presupposes an imbalance between the activity of the free oxygen radicals and the antioxidant defence mechanisms on the cellular level. The aim of the present study was to investigate if maternal diabetes in vivo, or high glucose in vitro alters the expression of the free oxygen radical scavenging enzymes superoxide dismutase (CuZnSOD and MnSOD), catalase and glutathione peroxidase in rat embryos during late organogenesis. We studied offspring of normal and diabetic rats on gestational days 11 and 12, and also evaluated day-11 embryos after a 48 hour culture period in 10 mM or 50 mM glucose concentration. Both maternal diabetes and high glucose culture caused growth retardation and increased rate of congenital malformations in the embryos. The CuZnSOD and MnSOD enzymes were expressed on gestational day 11 and both CuZnSOD, MnSOD and catalase were expressed on day 12 with increased concentrations of MnSOD transcripts when challenged by a diabetic milieu. There was a good correlation between mRNA, protein, and activity levels, suggesting that the regulation of these enzymes occurs primarily at the pretranslational level. Maternal diabetes in vivo and high glucose concentration in vitro induced increased MnSOD expression, concomitant with increased total SOD activity, and a tentative decrease in catalase expression and activity in the embryos. These findings support the notion of enhanced oxidative stress in the embryo as an etiologic agent in diabetic teratogenesis.
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PMID:Altered levels of scavenging enzymes in embryos subjected to a diabetic environment. 880 88

The pathogenesis of influenza virus infections of the lungs is in part mediated by oxidative stress. Such infections might therefore be expected to induce expression of stress-response genes and genes encoding antioxidant enzymes and to activate transcriptional regulatory proteins. Mice (C57B1/6 and C3H/HeJ) were infected intranasally with influenza virus A/PR/8/34 (H1N1). Expression of the genes encoding the antioxidant enzymes manganese superoxide dismutase (Mn- SOD), indoleamine-2, 3-dioxygenase (IDO), heme oxygenase-1, and glutathione peroxidase were increased in the lungs of virus-infected animals. Cu/ZnSOD and catalase mRNA were not induced by viral infection. Activation of the transcriptional regulatory proteins AP-1, C/EBP, and NF-kappa B (which are known to be affected by oxidant stress) was demonstrated by electrophoretic mobility shift assay after viral infection. In the case of MnSOD, despite increased gene expression enzyme activity was not increased. In contrast, for heme oxygenase-1 both mRNA and activity were increased. C3H/ HeJ and C57B1/6 mice, which are known to have different responses to other types of oxidant stress, also differed in their responses to viral infection. Induction of heme oxygenase-1 expression was greater in C57B1/6 mice than in C3H/ HeJ mice, although inhibiting this enzyme did not alter virus-induced mortality. In contrast, IDO was more strongly induced in C3H/HeJ mice. Activation of NF-kappa B was much more marked in C57B1/6 mice than in C3H/HeJ mice. Although virus replication and inflammatory responses were equivalent in the two strains, lung injury (as measured by wet-to-dry wt ratios) and mortality were greater in C3H/HeJ mice than in C57B1/6 mice, a difference that may be related to differing oxidant stress responses. Thus influenza pneumonia causes an oxidant stress response in the lungs, the nature of which is determined in part by the genetic background of the host.
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PMID:Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation. 884 86

This study examined the effects of glycocorticoids, insulin, thyroxine, and epinephrine upon the activities of CuZn- and Mn-superoxide dismutases (SOD), catalase, and glutathione peroxidase (GPX) and upon hydrogen peroxide production in rat macrophages obtained from the intraperitoneal cavity. The experiments were performed in vivo under conditions causing hormonal dysfunctions: adrenal demedullation, dexamethasone treatment, thyroidectomy, administration of L-tri-iodothyronine (T3) and L-thyroxine (T4), and diabetes. Macrophages were also cultured for 24 hr in the presence of dexamethasone, thyroid hormones, and insulin as to evaluate possible interferences caused in vivo by changes in other hormones. The results indicated that these hormones do control the activities of the antioxidant enzymes and hydrogen peroxide production both in vivo and in vitro. Insulin increased the activities of CuZn-SOD, catalase, and GPX and reduced that of Mn-SOD. Thyroid hormones raised the activities of CuZn- and Mn-SOD and decreased that of GPX, whereas glucocorticoids reduced both Mn-SOD and GPX. The removal of the adrenal medulla caused a decrease of Mn-SOD and GPX activities in the macrophages. Hydrogen peroxide production was increased by insulin and reduced by thyroid hormones and glucocorticoids. The changes in antioxidant enzyme activities caused by these hormones in macrophages may indicate important mechanisms for the establishment of impaired immune function in endocrine pathologies.
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PMID:Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages. 884 37

We studied the effect of age and calorie restriction on the expression of genes involved in antioxidant defenses in livers of young (4.5-6 months) and old (22 months) Emory mice fed a control (C) or restricted (R) diet. Specifically examined were catalase (CAT), glutathione peroxidase (Gpx), Cu/Zn and Mn superoxide dismutase (Cu/ZnSOD and MnSOD). As an indicator of oxidative damage to the tissues we measured lipid peroxidation. As indicators of oxidative stress we determined ubiquitin mRNA levels and endogenous high molecular weight (HMW) ubiquitin conjugates. Lower mRNA levels of ubiquitin (P < 0.05), CAT (P < 0.01) and Gpx (P < 0.01) were observed in tissues from young R versus C animals. The old C group had a lower CAT mRNA level (P < 0.0001) compared with young C. In the R group, age did not affect the CAT mRNA levels or Gpx mRNA levels; however, ubiquitin mRNA levels were higher (P < 0.05). No significant changes in Cu/Zn or MnSOD mRNA were observed with age or diet. Cu/ZnSOD protein levels were lower in the young R at 4.5 months (P < 0.05) than young C, and higher in the old R group versus old C (P < 0.05). CAT protein levels were higher in the old C versus old R (P < 0.05). Changes of HMW ubiquitin conjugates with age r diet were not significant. Of the four groups, the old R group showed the highest levels of lipid peroxidation.
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PMID:Effects of calorie restriction and aging on the expression of antioxidant enzymes and ubiquitin in the liver of Emory mice. 890 9

Reactive oxygen species (ROS) are mediators of cellular injury and play a putative role in the onset of hepatic damage during endotoxemia or sepsis. It has been suggested that induction of glucose-6-phosphate (G-6-P) dehydrogenase, the key enzyme of the hexose monophosphate shunt (HMS), may support ROS-producing or ROS-eliminating pathways in hepatic endothelial and Kupffer cells during endotoxemia. The aim of the study was to assess in vivo lipopolysaccharide (LPS)-induced alterations in rat gene expression of selected enzymes that are in functional relationship with the HMS. mRNA levels and activities of glucose transporter GLUT-1, Mn- and CuZn-dependent superoxide dismutases (Mn-SOD and CuZn-SOD), and Se-dependent glutathione peroxidase (Se-GPX) were determined. Cellular extracts were analyzed 7 or 22 h after injection of LPS (Escherichia coli, 2 mg/kg ip) or injection of saline. Exposure to LPS for 7 or 22 h caused a 10- to 25-fold increase in GLUT-1 mRNA levels in endothelial and Kupffer cells. In parenchymal cells, GLUT-1 mRNA expression was low, and LPS caused no marked changes. Cellular levels of Mn-SOD mRNA were 20-40 times greater in all hepatic cells from LPS-treated animals than in cells from control rats. LPS at 22 h increased Mn-SOD activity by 45% in endothelial cells but caused no significant changes in Kupffer or parenchymal cells. Message levels and enzyme activities of CuZn-SOD and Se-GPX were significantly elevated 22 h after LPS injection in endothelial cells only. Thus LPS results in marked upregulation of functionally related genes in hepatic cells. In endothelial cells, the simultaneous upregulation of GLUT-1, G-6-P dehydrogenase, Mn-SOD, CuZn-SOD, and Se-GPX may represent an important mechanism for accelerated elimination of ROS released from activated sinusoidal phagocytes. In Kupffer cells, upregulated GLUT-1 and G-6-P dehydrogenase, together with constitutively present SOD and lack of upregulated Se-GPX, suggest an elevated capacity to produce O2- and H2O2 that is consistent with primed bacterial killing.
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PMID:Endotoxin stimulates gene expression of ROS-eliminating pathways in rat hepatic endothelial and Kupffer cells. 892 96

An increase in antioxidant enzyme activity after acute exercise and exercise training have been reported by many investigators including our laboratory. This study was undertaken in order to determine whether an increase in activity of superoxide dismutase (MnSOD and CuZnSOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during exercise training was associated with the increased levels of respective mRNAs. Male Fisher-344 rats (age 77 weeks) were given exercise training for 9 weeks on the treadmill. Enzyme activity and mRNA's were measured in the heart tissue 23 hr after stopping exercise training. The heart tissues of exercised and sedentary control rats were used to isolate mRNAs encoding MnSOD, CuZnSOD, CAT and GSH-Px by northern blotting experiments. The intensities of mRNA bands were measured by densitometric scanning of the autoradiograms. Northern blot for tubulin was used to normalize the respective intensities. Compared to sedentary controls, the level of mRNAs of enzymes MnSOD, CAT and GSH-Px were found to increase by 126 +/- 5, 133 +/- 6, and 138 +/- 5 percent of sedentary control (mean +/- SEM) respectively, due to exercise training. Corresponding values for these enzyme activity were 153 +/- 19%, 255 +/- 7%, 133 +/- 2% of sedentary control. These results suggest that post-translational modification of these enzyme activity increased in response to exercise training more than increased transcription in aged rats.
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PMID:Comparative effects of exercise training on transcription of antioxidant enzyme and the activity in old rat heart. 895 Jan 34

The storage of subunit c of mitochondrial ATP synthase, other hydrophobic peptides, and autofluorescent pigment in both late infantile (CLN2) and juvenile (CLN3) neuronal ceroid lipofuscinosis, but not in infantile (CLN1), has raised the question of abnormal mitochondrial function. We now report a partial deficiency in three types of fatty acid oxidation in intact skin fibroblasts from CLN2 and CLN3 patients, but not CLN1. We observed a statistically significant 33% reduction in palmitate (beta-oxidation; mainly mitochondrial) and lignocerate (beta-oxidation; mainly peroxisomal), and a 50% reduction in phytanic acid (alpha-oxidation; mainly peroxisomal) in the absence of exogenous carnitine. In contrast, when we measured fatty acid beta-oxidation (lignoceric acid and palmitic acid), in the same human skin fibroblasts, following lysis in the presence of carnitine, we found no difference in enzyme activity among normal, CLN1, CLN2, and CLN3. However, we did observe a 40% reduction in peroxisomal particulate (bound) catalase activity in CLN1 and CLN2 fibroblasts, which typically results from organellar lipid accumulation or a membrane abnormality. However, total catalase levels were normal, and Western blot analysis of this and three other major oxidant protective enzymes (Mn-dependent superoxide dismutase [MnSOD], CuZn-dependent superoxide dismutase [CuZnSOD], and glutathione peroxidase) were normal in CLN1, CLN2, and CLN3, as well as in liver from an animal (English Setter dog) model for CLN, which shows similar pathology and subunit c storage. Our data showing differences between CLN1 and forms CLN2 and CLN3 suggest some type of mitochondrial membrane abnormality as the source of the pathology in CLN2 and CLN3.
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PMID:Mitochondrial abnormalities in CLN2 and CLN3 forms of Batten disease. 897 98

The oxidative stress related consequences of physical training at high altitude are not known. The hypothesis was tested that physical training and exposure to high altitude have adverse effects on free radical generation and activities of antioxidant enzymes. The present results showed that 4 weeks of exercise at an altitude of 4000 m increased the activity of Mn-SOD in both white and red types of skeletal muscle. The activities of Cu,Zn-SOD, catalase, and glutathione peroxidase, as well as the level of lipid peroxidation measured by TBARS and lipid hydroperoxides, did not change significantly. In contrast, the level of reactive carbonyl derivatives measured by anti-2,4-dinitrophenylhydrazone antibodies and spectrophotometry showed an increase in both types of muscle of altitude trained rats compared with sea level trained and control groups. It was suggested that the oxidative modification of certain amino acids is due to the increasing gap between activity of SOD and peroxide scavenging enzymes, which results in increases in the number of hydrogen peroxide molecules. Thus, since the mechanism of generation and/or the mode of action of radicals resulting in lipid peroxidation and protein oxidation appears to be different in vivo, both processes should be studied during oxidative stress.
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PMID:High altitude training increases reactive carbonyl derivatives but not lipid peroxidation in skeletal muscle of rats. 903 49


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