Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regional distribution and age-related change of Mn-, Cu/Zn-superoxide dismutase (SOD) and constitutive type of nitric oxide synthase (NOS) activities in the brain were determined using stroke-prone spontaneously hypertensive rats (SHRSP). In the hippocampus (HIP), Mn- and Cu/Zn-SOD activities in SHRSP of 31-week-old were significantly lower than those of 15-week-old or normotensive rats (WKY). From Mn-SOD immunohistochemical staining of several subfields of the HIP, our results suggested that SHRSP hippocampal CA1 was more vulnerable to oxidative stress compared with WKY and other subfields. In the 31-week-old SHRSP cerebral cortex (CC), the activities of Mn-, Cu/Zn-SOD and NOS were significantly lower than those in WKY. At this age, most of the SHRSP developed cerebral injuries. These observations indicated that hypertensive vascular disease observed in the SHRSP CC resulted from the decreased antioxidant capacity that is closely associated with the development of stroke and, in turn, shortened life span.
Neurosci Lett 1999 Sep 24
PMID:Age-related change of antioxidant capacities in the cerebral cortex and hippocampus of stroke-prone spontaneously hypertensive rats. 1050 47

We examined the effects of clofibric acid, a peroxisome proliferator, on the production of superoxide radicals, on the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and on the expression of superoxide dismutases (SODs) in the human HepG2 hepatoma cell line. To this end, HepG2 cells were treated for 1 or 5 days with 0.25, 0.50, or 0.75 mM clofibric acid. The production of superoxide radicals was only enhanced in HepG2 cells exposed for 5 days to the different clofibric acid concentrations. However, this overproduction of superoxide radicals was not accompanied by increased rates of lipid peroxidation, as the MDA and 4-HNE levels did not change significantly. Manganese (Mn) SOD activity was increased when HepG2 cells were treated for 1 day with 0.50 or 0.75 mM clofibric acid. For this duration of treatment, no change was observed in total SOD and copper/zinc (Cu/Zn) SOD activities. For a 5-day treatment, total SOD and MnSOD activities as well as the enzyme apoprotein and MnSOD mRNA levels increased whatever the clofibric acid concentration used. This transcriptional induction of the MnSOD gene was correlated with an activation of the activator protein-1 transcription factor for 1 and 5 days of treatment, but was independent of nuclear factor-kappa B and of peroxisome proliferator-activated receptor. On the other hand, the PP exerted very little effect if any on Cu,ZnSOD expression. In contrast to rodent data, PP treatment of human hepatoma cells induces MnSOD expression.
Biochem Pharmacol 1999 Sep 15
PMID:Effects of the peroxisome proliferator clofibric acid on superoxide dismutase expression in the human HepG2 hepatoma cell line. 1050 55

The activities of superoxide dismutase (SOD) isoenzymes were measured in fourth instar larvae of Chironomus riparius Mg. Three types of superoxide dismutase were identified: Cu,Zn-SOD in hemolymph and postmitochondrial fraction; Mn-SOD in mitochondrial fraction and presumably Fe-SOD in postmitochondrial fraction. The latter could have an endosymbiotic or a parasitic origin. Extracellular and cytosolic SOD activities, especially Cu,Zn-SOD, tended to increase in the last phase of larval development, independently of protein or hemoglobin contents. This supposes that SOD activity in Ch. riparius larvae is probably activated at the end of fourth instar stage. Cu,Zn-SOD and Mn-SOD activities showed a significant increase under severe hypoxia and slight hyperoxia. Oxygen radical scavengers such as SOD may play a role in the increased tolerance of Ch. riparius to oxidative stress. These results suggest that the specific induction of some SOD isoenzymes could be used as a biomarker of environmental disturbance such as oxidative stress initiated by xenobiotics.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1999 Sep
PMID:Characterization of superoxide dismutase activity in Chironomus riparius Mg. (Diptera, Chironomidae) larvae--a potential biomarker. 1057 51

A current hypothesis explaining the toxicity of superoxide anion in vivo is that it oxidizes exposed [4Fe-4S] clusters in certain vulnerable enzymes causing release of iron and enzyme inactivation. The resulting increased levels of "free iron" catalyze deleterious oxidative reactions in the cell. In this study, we used low temperature Fe(III) electron paramagnetic resonance (EPR) spectroscopy to monitor iron status in whole cells of the unicellular eukaryote, Saccharomyces cerevisiae. The experimental protocol involved treatment of the cells with desferrioxamine, a cell-permeant, Fe(III)-specific chelator, to promote oxidation of all of the "free iron" to the Fe(III) state wherein it is EPR-detectable. Using this method, a small amount of EPR-detectable iron was detected in the wild-type strain, whereas significantly elevated levels were found in strains lacking CuZn-superoxide dismutase (CuZn-SOD) (sod1 delta), Mn-SOD (sod2 delta), or both SODs, throughout their growth but particularly in stationary phase. The accumulation was suppressed by expression of wild-type human CuZn-SOD (in the sod1 delta mutant), by pmr1, a genetic suppressor of the sod delta mutant phenotype (in the sod1 delta sod2 delta double knockout strain), and by anaerobic growth. In wild-type cells, an increase in the EPR-detectable iron pool could be induced by treatment with paraquat, a redox-cycling drug that generates superoxide. Cells that were not pretreated with desferrioxamine had Fe(III) EPR signals that were equally as strong as those from treated cells, indicating that "free iron" accumulated in the ferric form in our strains in vivo. Our results indicate a relationship between superoxide stress and iron handling and support the above hypothesis for superoxide-related oxidative damage.
J Biol Chem 2000 Sep 22
PMID:Yeast lacking superoxide dismutase(s) show elevated levels of "free iron" as measured by whole cell electron paramagnetic resonance. 1088 31

At least five different transgenic approaches have been applied to the study of Drosophila aging. There are two single component systems: transgenes with native (normal) promoters and transgenes with heterologous promoters; as well as three binary systems: 'GAL4/UAS', 'FLP-out' and 'tet-on'. These approaches vary in ability to meet several technical challenges, and the relative advantages and disadvantages of each are discussed. Using these techniques, over-expression of the hsp70, Cu/ZnSOD and MnSOD genes has each been demonstrated to increase Drosophila life span.
Mech Ageing Dev 2000 Sep 01
PMID:Transgenic methods for increasing Drosophila life span. 1098 20

Previous studies, conducted on experimental animals, have indicated that reactive oxygen species (ROS) are involved in the aging process. The objective of this work was to study the relationship between oxidative damage and human skeletal muscle aging, measuring the activity of the main antioxidant enzymes superoxide dismutase (total and MnSOD), glutathione peroxidase (GPx) and catalase in the skeletal muscle of men and women in the age groups: young (17-40 years), adult (41-65 years) and aged (66-91 years). We also measured glutathione and glutathione disulfide (GSH and GSSG) levels and the redox index; lipid peroxidation and protein carbonyl content. Total SOD activity was lower in the 66-91 year-old vs. the 17-40 year-old men; MnSOD activity was significantly greater in 66-91 year-old vs. 17-40 year-old women. GPx activity remained unchanged. The activity of catalase was lower in adults than in young men but higher in the aged. We observed no changes in GSH levels and significantly higher GSSG levels only in aged men vs. adult men, and a significant decrease in aged women vs. aged men. The protein carbonyl content increased significantly in the 41-65 and 66-91 year-old vs. the 17-40 year-old men. Finally, young women have lower lipid peroxidation levels than young men. Significantly higher lipid peroxidation levels were observed in aged men vs. both young and adult men, and the same trend was noticed for women. We conclude that oxidative damage may play a crucial role in the decline of functional activity in human skeletal muscle with normal aging in both sexes; and that men appear to be more subject to oxidative stress than women.
Free Radic Res 2000 Sep
PMID:Age and sex differences in human skeletal muscle: role of reactive oxygen species. 1099 82

Nitroxyl (NO(-)) may be produced by nitric-oxide synthase and by the reduction of NO by reduced Cu,Zn-SOD. The ability of NO(-) to cause oxidations and of SOD to inhibit such oxidations was therefore explored. The decomposition of Angeli's salt (AS) produces NO(-) and that in turn caused the aerobic oxidation of NADPH, directly or indirectly. O(2) was produced concomitant with the aerobic oxidation of NADPH by AS, as evidenced by the SOD-inhibitable reduction of cytochrome c. Both Cu,Zn-SOD and Mn-SOD inhibited the aerobic oxidation of NADPH by AS, but the amounts required were approximately 100-fold greater than those needed to inhibit the reduction of cytochrome c. This inhibition was not due to a nonspecific protein effect or to an effect of those large amounts of the SODs on the rate of decomposition of AS. NO(-) caused the reduction of the Cu(II) of Cu,Zn-SOD, and in the presence of O(2), SOD could catalyze the oxidation of NO(-) to NO. The reverse reaction, i.e. the reduction of NO to NO(-) by Cu(I),Zn-SOD, followed by the reaction of NO(-) with O(2) would yield ONOO(-) and that could explain the oxidation of dichlorofluorescin (DCF) by Cu(I),Zn-SOD plus NO. Cu,Zn-SOD plus H(2)O(2) caused the HCO(3)(-)-dependent oxidation of DCF, casting doubt on the validity of using DCF oxidation as a reliable measure of intracellular H(2)O(2) production.
J Biol Chem 2001 Sep 21
PMID:Copper,zinc superoxide dismutase as a univalent NO(-) oxidoreductase and as a dichlorofluorescin peroxidase. 1146 12

Manganese superoxide dismutase Mn-SOD plays a major role in protecting mitochondria from oxidative damage. Overexpression of Mn-SOD maintains cell survival under conditions that lead to apoptotic death. In addition to the antioxidative enzyme, platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation by activating survival signaling pathways in various cells. Here we show that PDGF induced the expression of the Mn-SOD gene in NIH3T3 cells, and its induction was associated with early growth response-1 (Egr-1), a transcription factor. An electrophoretic mobility shift assay demonstrated that Egr-1 bound to the proximal promoter of the Mn-SOD gene in response to PDGF. The proximal promoter region of Mn-SOD was shown to be transcriptionally responsive to both basal and PDGF stimulation by transfection studies. Forced expression of Egr-1 in the cells activated Mn-SOD transcription in a dose-dependent manner. The pathway by which PDGF induced Egr-1 involved the mitogen-activated protein kinase kinase-1 (MEK1) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), because the effect of PDGF on the induction of Egr-1 was blocked by U0126, a specific MEK1 inhibitor. These findings indicate that the induction of Mn-SOD is part of the anti-apoptotic properties mediated by PDGF.
FASEB J 2001 Sep
PMID:Early growth-responsive-1-dependent manganese superoxide dismutase gene transcription mediated by platelet-derived growth factor. 1151 24

The aim of this study was to examine three types of superoxide dismutase (SOD) in plasma after burns, and especially to clarify the characteristics of plasma extracellular SOD (EC-SOD) in burned patients. A total of 71 blood samples were collected from 18 patients on arrival, day 1, day 3 and day 5 after burns. We measured three types of SOD (Mn, Cu/Zn, EC) in plasma using ELISA, and the relationships among the three types of SOD concentrations were examined. We next analyzed the characteristics of plasma EC-SOD using stepwise multivariate regression analysis. Any plasma SOD isoenzyme concentration measured after burns was beyond the normal range and EC-SOD accounted for the major part of plasma SODs. EC-SOD and Cu/Zn-SOD were positively correlated, whereas Mn-SOD was not related to the other SODs. Also, plasma EC-SOD was significantly related to existence of inhalation injury, %TBSA and age, respectively. The plasma EC-SOD might therefore play some roles in the pathophysiology of burned patients.
Burns 2001 Sep
PMID:Characteristics of plasma extracellular SOD in burned patients. 1152 51

[reaction: see text]. The riboflavin-catalyzed photooxidation of 2',3',5'-tri-O-acetyl-8-oxo-7,8-dihydroguanosine generates a radical intermediate that is competitively trapped by H(2)O, O2(-)(*), or O(2). The products of H(2)O trapping have been previously described as the spiroiminodihydantoin (pH >or= 7) and iminoallantoin/guanidinohydantoin (pH < 7) nucleosides. Trapping by O2(-)(*) leads to the oxaluric acid (pH <or= 7) and imidazolone (pH >or= 8.6) pathways (R' ', R' ' = H or 2,3,5-tri-O-Ac-ribofuranosyl). The pH-dependent role of superoxide was probed using Mn-SOD and compared to guanosine and 8-methoxyguanosine photooxidation.
Org Lett 2001 Sep 06
PMID:The pH-dependent role of superoxide in riboflavin-catalyzed photooxidation of 8-oxo-7,8-dihydroguanosine. 1152 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>