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)

Lipid peroxidation has been considered one of the most important factors involved in the pathogenesis of neuronal damage following subarachnoid hemorrhage. In the brain, the protective systems most involved against peroxidative and free radicals generated reactions are superoxide-dismutase (SOD) and glutathione-peroxidase (GSH-Px). Since these activities are subjected to a significant reduction following experimental SAH induction in rats, we investigated in the present study if the beneficial effect of high-dose methylprednisolone (MP) in inhibiting lipid peroxidative processes in SAH is possibly linked to an influence on anti-oxidant enzymatic activities. In brain cortex, after MP treatment, Cu-Zn SOD activity in the early phase and more dramatically in the late phase after SAH was restored (4.06 +/- 0.06 and 4.07 +/- 0.14 enzymatic units/mg of protein, respectively) if compared to hemorrhagic non-treated controls (3.69 +/- 0.16 and 2.96 +/- 0.06 enzymatic U/mg of protein) while Mn-SOD and GSH-Px activities were improved in treated animals only in the early and late phases after SAH, respectively. In the hippocampus, in treated rats Cu-Zn activity was partially restored only at 6 h, while Mn-SOD activity recovered at 48 h after SAH; no significant changes in GSH-Px activity were found in treated animals at any time. In the brain stem, in treated animals, Cu-Zn SOD activity was restored in the early phase (3.86 +/- 0.12 enzymatic U/mg of protein) up to control values of non-hemorrhagic rats (3.44 +/- 0.30 enzymatic U/mg of protein), while GSH-Px activity recovered in the late phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of high-dose methylprednisolone on anti-oxidant enzymes after experimental SAH. 140 93

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 have previously shown that the polyethylene glycol conjugated superoxide dismutase (SOD), which has a plasma half-life of more than 24 h, protects the blood perfused rabbit heart against injury during ischaemia and reperfusion. However, the profile for the dose-dependency of protection was bell-shaped with loss of efficacy below 6000 and above 30,000 U/kg. In the present study, isolated rabbit hearts, perfused with blood from support rabbits, were subjected to a 2 min infusion with St Thomas' Hospital cardioplegic solution followed by 60 min of global ischaemia (37 degrees C) and 60 min of reperfusion. PEG-SOD was administered 1 h or 12-24 h before ischaemia. We assessed the effect of PEG-SOD on ischaemia- and reperfusion-induced changes in: (i) the tissue content of reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) and (ii) the activity of CuZn-SOD, Mn-SOD and glutathione peroxidase and reductase (GPD and GRD). Ischaemia and reperfusion reduced tissue GSH content by 70% and increased GSSG content by 400% (from their fresh aerobic values of 13.1.9 and 0.09 +/- 0.01 nmol/mg protein, respectively). PEG-SOD, given intravenously at various doses to donor and support rabbits 1 h or 12-24 h before ischaemia, protected against these changes with a bell-shaped dose-response relationship. Thus, with 0, 3000, 6000, 12,000, 30,000 and 60,000 U/kg, GSH content was 4.1 +/- 0.4, 4.8 +/- 0.4, 8.5 +/- 0.5, 12.3 +/- 1.6, 12.3 +/- 1.6 and 5.0 +/- 0.5 nmol/mg protein in the 1 h pretreatment group and 4.1 +/- 0.4, 4.2 +/- 0.5, 10.4 +/- 1.5, 11.2 +/- 1.1, 11.4 +/- 0.7 and 4.7 +/- 0.6 nmol/mg protein in the 12-24 h pretreatment group (means +/- S.E.M.). For GSSG the corresponding values were 0.36 +/- 0.04, 0.34 +/- 0.03, 0.12 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.41 +/- 0.03 nmol/mg protein for the 1 h group and 0.36 +/- 0.04, 0.35 +/- 0.02, 0.15 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.34 +/- 0.02 nmol/mg protein for the 12-24 h group. Ischaemia and reperfusion had no effect on tissue MDA content or CuZn-SOD, GDP and GRD activity, and in general, PEG-SOD also lacked significant effect on any of these variables at any dose studied. However, Mn-SOD activity was severely reduced by ischaemia and reperfusion (from 42 +/- 7 U/mg protein in fresh aerobic controls to 6 +/- 1 U/mg protein at the end of reperfusion).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:PEG-SOD and myocardial antioxidant status during ischaemia and reperfusion: dose-response studies in the isolated blood perfused rabbit heart. 143 18

Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age-related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region-specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined.
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PMID:Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat. 143 48

We have studied the pattern of enzymatic antioxidant activities (Cu-Zn superoxide dismutase = SOD, Mn-SOD and glutathione peroxidase = GSH-Px) in brain cortex of rats subjected to experimental induction of subarachnoid hemorrhage (SAH), in order to discuss the modifications of antioxidant systems in relation to the development of lipid peroxidative processes occurring in brain cortex. Lipid peroxidation (quantified as TBRAs content) did not show significantly changes, when sham-operated and SAH rats were compared; meanwhile at 1 hour TBARs content shows an increasing trend both in sham-operated and hemorrhagic rats. The release of leukotriene C4, the major lipoxygenase metabolite, is significantly enhanced at 1, 6 and 48 hours after SAH induction. Cu-Zn SOD activity is significantly reduced at 6 and 48 hours after SAH induction; Mn-SOD activity is significantly affected at 1, 6 and 48 hours after the hemorrhage. GSH-Px activity is significantly reduced only in the late phase (48 hours) after SAH. The results of the present study suggests that: (a) in brain compartment a significant reduction of antioxidant enzymatic activities is related to the increasing trend of enzymatic lipid peroxidation; (b) antioxidant activities showed specific time-dependent modifications: Cu-Zn and Mn SOD activities, which are specific scavengers of superoxide radicals, showed an early impairment, while GSH-Px activity is significantly reduced only after 48 hours; (c) the enhancement of enzymatic lipid peroxidation via the lipoxygenase pathway seems to play a primary role in brain response to SAH. These results should be considered the rationale for pharmacological treatment with antioxidant compounds for brain protection against detrimental effects of subarachnoid hemorrhage.
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PMID:Brain damage following subarachnoid hemorrhage: the imbalance between anti-oxidant systems and lipid peroxidative processes. 150 Sep 55

In the present study, we have assayed the enzymatic activity of Cu,Zn-SOD, Mn-SOD, GSH-Px, GSH-Red, Cat, and G6PD in rat retina as a function of age. Conjugated diene levels and MDA formation were also determined. The conjugated diene levels in rat retina were found to increase significantly with age, accompanied by a marked decrease in GSH-Px and Cat activities. No age-related change in MDA levels and in GSH-Red and G6PD activity was found, whereas a significant increase in SOD activity was observed between 1 and 4 months. Decreased GSH-Px and Cat activity is related to increased lipid peroxidation with age.
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PMID:Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age. 160 66

1. The activity of antioxidant defense enzymes (SOD, CAT, GSH-Px and GST) was analysed during the autumn and winter in the ground squirrel adapted to 30 degrees C and subsequently exposed to cold for 6 and 24 hr. 2. The liver CAT activity as well as the IBAT CAT and GSH-Px activities differed between animals adapted to 30 degrees C, studied in autumn, and those studied in winter. 3. MnSOD activity in the liver was increased in autumn but decreased in winter after 6 hr cold exposure reaching the control level 24 hr later. Cold exposure induced a decrease in CAT activity (except after 24 hr cold exposure in winter) and an increase in GSH-Px activity. Lower GST activity was found after 24 hr exposure to cold in winter. 4. The IBAT SOD activity decreased under the influence of cold during both seasons with a tendency to return to the control level only in winter. Cold exposure produced a decrease in GST in both seasons and CAT activity in autumn. GSH-Px activity was increased in winter only. 5. The results indicate a seasonal dependence of the activity of antioxidant defence enzymes in the ground squirrel. Seasonal influence was evidenced in animals exposed to cold as well.
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PMID:Seasonal dependence of the activity of antioxidant defence enzymes in the ground squirrel (Citellus citellus): the effect of cold. 161 72

HA-1 hamster fibroblasts receiving fresh media every 24 h were continuously passaged in progressively increasing O2 concentrations for 18 mo (designated O2R95). These cells were significantly more resistant than parental HA-1 to clonogenic inactivation mediated by 95% O2 without media replacement. The O2R95 cell line exhibited increases in the activities of catalase (CAT), Mn superoxide dismutase (MnSOD), Cu,Zn superoxide dismutase (Cu,Zn SOD), and glutathione peroxidase (GPx). O2R95 cells demonstrated uniformly distributed increased staining for CAT, MnSOD, Cu,Zn SOD, and GPx proteins, as determined by immunohistochemistry. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a toxic byproduct of lipid peroxidation implicated in mechanisms of O2 toxicity, was examined in HA-1 and O2R95 cell lines. O2R95 cells were significantly more resistant to 4HNE cytotoxicity, which was accompanied by a significant increase in 4HNE metabolism. O2R95 cells also demonstrated an increase in total glutathione (GSH) and glutathione S-transferase (GST) activity, an enzymatic system believed to be involved with 4HNE metabolism. Furthermore, homogenates from O2R95 cells consumed greater quantities of 4HNE in the presence of NADPH (but not NADH, NAD+, or NADP+), suggesting that an enzyme(s) utilizing NADPH contributes to 4HNE metabolism, resistance to 95% O2 and 4HNE as well as increased total GSH, antioxidant enzyme activities, and NADPH-dependent metabolism of 4HNE, persisted in O2R95 cells for 75 days of growth in 21% O2. These findings are compatible with the hypothesis that aldehydic byproducts of lipid peroxidation contribute to mechanisms of O2 toxicity and the selective pressure exerted by exposure of cells to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A stable O2-resistant cell line: role of lipid peroxidation byproducts in O2-mediated injury. 161 58

Oxidants are toxic, but at low doses they can stimulate rather than inhibit the growth of mammalian cells and play a role in the etiology of cancer and fibrosis. The effect of oxidants on cells is modulated by multiple interacting antioxidant defense systems. We have studied the individual roles and the interaction of Cu,Zn-superoxide dismutase (SOD) and catalase (CAT) in transfectants with human cDNAs of mouse epidermal cells JB6 clone 41. Since only moderate increases in these enzymes are physiologically meaningful, we chose the following five clones for in-depth characterization: CAT 4 and CAT 12 with 2.6-fold and 4.2-fold increased catalase activities, respectively, SOD 15 and SOD 3 with 2.3-fold and 3.6-fold increased Cu,Zn-SOD activities, respectively, and SOCAT 3 with a 3-fold higher catalase activity and 1.7-fold higher Cu,Zn-SOD activity than the parent JB6 clone 41. While the increases in enzyme activities were moderate, the human cDNAs were highly expressed in the transfectants. As demonstrated for the clone SOD 15, this discordance between message concentrations and enzyme activities may be due to the low stability of the human Cu,Zn-SOD mRNA in the mouse recipient cells. According to immunoblots the content of Mn-SOD was unaltered in the transfectants. While the activities of glutathione peroxidase were comparable in all strains, the concentrations of reduced glutathione (GSH) were significantly lower in SOD 3 and SOD 15. This decrease in GSH may reflect a chronic prooxidant state in these Cu,Zn-SOD overproducers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The balance between Cu,Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. 165 93

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


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