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)

In subcellular systems, doxorubicin hydrochloride (ADR) leads to the generation of reactive oxygen species such as superoxide anion. Because reactive oxygen species have been shown to be important mediators of glomerular injury in several animal models, we sought to determine whether reactive oxygen species play a significant role in the pathogenesis of ADR-induced nephrotic syndrome in the rat. Rats pretreated with a variety of free radical scavengers (superoxide dismutase conjugated to polyethylene glycol [PEGSOD], catalase, catalase plus PEGSOD, dimethylsulfoxide, desferoxamine, or n-acetyl cysteine) had no significant reduction in proteinuria at 3 weeks after ADR administration when compared with rats receiving ADR in the absence of scavengers. No evidence was seen of increased lipid peroxidation or depletion of reduced glutathione in renal cortex tissue obtained up to 24 hours after administration of ADR. No changes were seen in the renal cortical levels of either enzyme activity or immunoreactive protein for the endogenous antioxidant enzymes superoxide dismutase (either the Mn or CuZn forms) or catalase after ADR. Total and MnSOD activities in glomeruli isolated from rats after ADR administration fell significantly, though CuZnSOD activity was increased. The effect of ADR on cultured rat mesangial or epithelial cells was also evaluated. ADR inhibited growth of both cell types at concentrations of approximately 5 to 10 mumol/L, an order of magnitude below the reported Michaelis-Menten constant for ADR-induced superoxide production. The growth inhibitory effect could not be prevented in either cell type by treatment with PEGSOD, catalase, or PEGSOD plus catalase. This combination of results from in vivo and in vitro studies provides no evidence for an important role of reactive oxygen species in ADR nephrosis and suggests that other known mechanisms of ADR cytotoxicity, such as interference with DNA metabolism, mediate the glomerular injury.
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PMID:Evaluation of the role of reactive oxygen species in doxorubicin hydrochloride nephrosis. 194 May 84

We examined the effect of glucocorticoid on intrinsic glomerular antioxidant enzyme (AOE) activities. Munich-Wistar rats were treated with daily i.p. injection of vehicle or methylprednisolone [MP, 15 mg/kg body wt, (MP15)] either for three days or nine days. Glomeruli isolated from rats given MP15 had significantly higher activities of total (T-) and manganese (Mn-) superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase than vehicle-treated rats (P less than 0.05). MP15-treated rats were subjected to intrarenal arterial infusion of hydrogen peroxide (35 mumol over 1 hr). Values for urinary protein excretion rate (UprV) after hydrogen peroxide infusion were markedly lower in rats pretreated with MP15 for both three days and nine days than in untreated rats (109 +/- 18 and 55 +/- 24 vs. 416 +/- 73 micrograms/min, respectively, both P less than 0.005). To test whether the same therapeutic intervention attenuates reactive oxygen species (ROS)-mediated glomerular injury in another model, rats given a single i.v. dose of puromycin aminonucleoside (PAN) (50 mg/kg body wt) were treated with daily i.p. injection of vehicle or MP15. Two days after PAN administration, when compared to vehicle-treated controls, PAN rats given MP15 had significantly higher activities of Mn-SOD, GSH-Px and catalase. After eight days of PAN injection, T- and Mn-SOD activities were, likewise, significantly higher in MP15- than vehicle-treated PAN rats. PAN rats given MP15 also had substantially less proteinuria, compared to PAN rats given vehicle alone, UprV averaging 32.3 +/- 9.4 versus 159.0 +/- 13.8 mg/24 hr (P less than 0.05). Elevated glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in rats treated with MP15. Moreover, epithelial foot process fusion and cell vacuolization seen in vehicle-treated PAN rats were markedly attenuated in MP15-treated PAN rats. These data indicate that the mechanism for therapeutic effect of glucocorticoids on ROS-mediated renal injuries includes an enhancement of endogenous glomerular AOE activities, which attenuates lipid peroxidation of glomerular tissue.
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PMID:Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries. 194 78

As an animal model of human Parkinson's disease 250 micrograms of 6-Hydroxydopamine was injected intraventricularly in the rats. At 24 h, 48 h, 7th and 14th day after injection, the levels of dopamine, norepinephrine, Cu, Zn- and Mn- superoxide dismutase (SOD), catalase as well as the lipid peroxidative products in the striatum, midbrain and hypothalamus were determined. Our data showed that catecholamines decreased persistently, catalase and Mn-SOD decreased concomitantly, Cu, Zn-SOD, however, remained, unchanged. Lipid peroxidative products increased shortly after injection, then subsided. Our result suggests that lipid peroxidation might be involved in the degenerative process of neurons in Parkinson's disease.
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PMID:[Effect of 6-hydroxydopamine on cerebral catecholamines, lipid peroxidation and antioxidant enzymes in rats-concerned with pathogenesis of Parkinson's disease]. 195 95

We examined the influence of dehydroepiandrosterone (DHEA), a beta-agonist, and exercise training on enzymes that detoxify toxic oxygen species. Feeding 0.4% DHEA decreased hepatic cytosolic (c) selenium-dependent glutathione peroxidase (GPX), (-26%, P less than 0.0001) and increased hepatic mitochondrial (m) Mn superoxide dismutase (SOD), (+38%, P less than 0.001). DHEA decreased myocardial c-GPX (-21%, P less than 0.05) when compared to a beta-agonist (beta A; L644969 Merck and Co.) fed at 5 ppm but neither differed from the Control (C). In contrast, the beta A increased hepatic m-GPX (+25%, P less than 0.05). In skeletal muscle, DHEA and beta A decreased muscle c-GPX by 20 and 12%, respectively (P less than 0.0009). DHEA increased both muscle (+20%, P less than 0.01) and myocardial (+20%, P less than 0.05) c-glutathione S-transferase (GST) over beta A (+20%, P less than 0.01) but neither was significantly different from C. Similar to DHEA, chronic training (Tr) (1 h/day, 5 days/week at 27 m/min, 15% grade on treadmill) decreased hepatic c-GPX (-16%, P less than 0.003). Tr elevates muscle c-GPX (+36%, P less than 0.05) in C. Tr increased myocardial c-GPX by 28% in the beta A-treated rats, whereas Tr decreased myocardial c-GPX by 22% in the C (P less than 0.05, interaction). One hour of acute exercise (Ex) (70% VO2 max relative work load) decreased hepatic homogenate catalase (-12%, P less than 0.02) and increased hepatic m-Mn SOD (+28%, P less than 0.03). Ex decreased myocardial c-GST (P less than 0.05) only in the DHEA-treated rats. DHEA and Tr may improve efficiency of oxygen utilization at the tissue level with lower antioxidant enzyme activity in liver and locally protective up-regulation in muscle. beta A stresses oxygen utilization systems and liver responds by up-regulation of antioxidant enzymes. The increase in myocardial c-GPX activity in the beta A-treated group may be a protective effect against indirect catecholamine-induced myocardial necrosis which results from free radical generation.
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PMID:Dehydroepiandrosterone and a beta-agonist, energy transducers, alter antioxidant enzyme systems: influence of chronic training and acute exercise in rats. 198 Apr 4

Pretreatment or "priming" with vincristine (VcR) has been documented to radioprotect animals from whole body irradiation by accelerating recovery of hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but the marked similarities between priming with VcR and with immune stimulants such as endotoxin and glucan have led to speculation that VcR may be inducing such radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The radioprotective ability of these cytokines, in turn, has been linked to an induction of the antioxidant enzyme manganese superoxide dismutase (Mn SOD). To establish whether priming with VcR is associated with induction of antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity. Furthermore, this increase occurs at the time VcR priming has been demonstrated previously to exhibit maximal radioprotection, suggesting that it may be contributing factor. However, VcR priming has been demonstrated to radioprotect both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD activity (or the other enzymes monitored) was found in the tumor-bearing group. Rather, the presence of tumor significantly suppressed antioxidant enzyme activity. Collectively, the present data suggest that it is unlikely that increased antioxidant enzyme activity is directly involved in the VcR priming response.
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PMID:Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice following vincristine treatment. 199 2

The activities of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione S-transferases, GSSG reductase, thiol transferases, gamma glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase, and the concentrations of H2O2 and reduced and oxidized glutathione were determined in the various developmental stages of houseflies. Housefly development was correlated with a progressive increase of cellular oxidizing equivalents and a loss of cellular reducing capacity. The loss of reducing equivalents appeared to result from a decrease in the activity of enzymes involved in glutathione and NADPH synthesis and a concomitant increase in glutathione-oxidizing enzymes. Relatively little change was observed in SOD activity during housefly development; however, the electrophoretic pattern of MnSOD varied in a manner specific to developmental stage. A striking increase in H2O2 concentration occurred prior to pupation possibly due to changes in substrate catabolism. These results support the hypothesis that the cellular environment becomes progressively more oxidizing during development.
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PMID:Developmental patterns in the antioxidant defenses of the housefly, Musca domestica. 199 75

Antioxidant enzyme levels were determined in kidneys during estrogen-induced cortical renal tumorigenesis in male Syrian hamsters. The activity of these enzymes in renal tumors were compared to those in the kidney cortex of untreated male castrated hamsters of different ages and in age-matched animals treated with diethylstilbestrol (DES) for varying periods. A transient increase in kidney Mn superoxide dismutase (MnSOD) and total SOD activity was seen after 1.5 and 3.1 months of DES treatment compared to untreated controls. However, after 4.4 months of DES exposure the activities of these antioxidant enzymes fell below untreated levels. The level of MnSOD and CuZnSOD was 3- to 10-fold lower compared to castrated male renal cortical values in DES-induced primary, serially transplanted and in autonomous renal tumour variants. Catalase activity declined steadily at 1.5 to 4.4 months of DES treatment. Low levels of catalase activity were found in all tumors examined. In general, Western blot analysis of immunoreactive proteins confirmed these findings, indicating that the low enzyme activities were due to low levels of enzyme proteins. Immunohistochemistry of the earliest tumor foci exhibited negligible antioxidant enzyme activity. The levels of these antioxidant enzymes were similar in all tumors surveyed, both primary and autonomous variants and in newborn kidneys, and they were about 10-fold lower than in normal kidney cortex or isolated proximal tubules.
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PMID:Superoxide dismutase and catalase levels during estrogen-induced renal tumorigenesis, in renal tumors and their autonomous variants in the Syrian hamster. 204 4

Cu,Zn superoxide dismutase (Cu,Zn-SOD; EC 1.15.1.1) is known to be inhibited slowly by H2O2. Using EPR and the spin traps 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN), we have shown that Cu,Zn-SOD catalyzes the formation of "free" .OH radicals from H2O2 in pH 7.6 bicarbonate buffer. Supporting evidence includes the following: (i) H2O2 and active Cu,Zn-SOD are required to yield significant signals from spin-trap-OH adducts. (ii) With O2-., Cu,Zn-SOD causes the appearance of intense resonance signals due to DMPO-OH adducts. These signals were inhibited strongly by catalase. (iii) With H2O2, Cu,Zn-SOD, and DMPO, radical scavengers formate and azide, but not ethanol, decrease DMPO-OH signals while causing new intense signals due to their corresponding DMPO-radical adducts. Failure of ethanol to quench DMPO-OH signals is discussed in light of the positively charged active channel of the enzyme. (iv) With PBN as a spin trap, ethanol quenches .OH radical signals and yields PBN-trapped hydroxyethyl radical signals. (v) Mn-SOD does not catalyze "free" .OH radical formation and it also exerts no effect on the signals of DMPO-OH adducts when added together with the Cu,Zn-SOD. The capacity of Cu,Zn-SOD to generate "free" .OH radicals from H2O2 may in part explain the biological damage associated with elevated intracellular SOD activity.
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PMID:Copper, zinc superoxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide. 216 16

The antioxidant defenses of the liver, erythrocytes, blood plasma, and interscapular brown adipose tissue (IBAT) of male ground squirrels were compared with those of male rats kept under identical conditions and fed the same diet. Superoxide dismutase (SOD), ascorbate, vitamin E, catalase, glutathione, and enzymes of glutathione metabolism were measured. In general, antioxidant defenses in erythrocytes were lower in ground squirrels than in rats. The same was true in liver, except that catalase-specific activity was higher. In IBAT, ascorbate, vitamin E, catalase, and glutathione reductase were higher than in rat and more of the SOD activity present was cyanide-insensitive (MnSOD). It is suggested that IBAT in ground squirrels may need a relatively greater antioxidant defense because of its important role in thermogenesis, especially in reawakening from hibernation. No major differences in antioxidant defenses between male and female ground squirrels were observed, except that the SOD activity of IBAT was higher in females.
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PMID:Antioxidant defenses in the ground squirrel Citellus citellus. 1. A comparison with the rat. 229 34

Antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total glutathione concentration were determined in guinea pig lung and liver over the final period of gestation (days 50-68) and at several ages post-partum. Pulmonary antioxidant capacity increased markedly over the final days of gestation, individual changes ranging from 29% (glutathione) to 198% (GSH-Px). Liver antioxidant capacity was always 4-fold to 10-fold greater than that of the lung and exhibited very similar developmental profiles to those observed in the lung. From day 60 gestation to term (68 days), activity of the liver antioxidants increased, ranging from 246% (CAT) to 610% (glutathione). A number of antioxidants in both lung and liver exhibited either immediate pre- or post-birth decreases in activity. These falls could not be attributed to the way in which the results were expressed: i.e. they were similar, expressed per unit DNA, per unit protein, or per g wet wt. Following birth, liver antioxidant capacity increased such that the highest enzyme activities or glutathione concentration were recorded at 66 days post-partum. In lung, only Mn-SOD and glutathione exhibited higher levels at 66 days postpartum than at birth. In combination, these results of pulmonary and hepatic antioxidant enzyme activity indicate that the lung is not unique in acquiring increased antioxidant protection in the final period of gestation. They also suggest that a tissue's antioxidant requirement is dictated more by metabolic rate (hence free radical production) than incident partial pressure of oxygen.
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PMID:Developmental expression of antioxidant enzymes in guinea pig lung and liver. 235 Oct 72


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