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)

Hypertension, cigarette smoking, and nicotine augment the clinical significance of other risk factors associated with cardiovascular diseases by mechanisms which are poorly understood. Since altered trace element metabolism and antioxidant status have also been implicated in these diseases, the present study investigated the interaction of nicotine treatment and hypertension on tissue trace element concentrations and select indices of antioxidant status. Spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with nicotine, via a time release tablet at an average rate of 75 micrograms/h for 6 weeks. Systolic blood pressure in nicotine-treated SHRs was significantly higher at weeks 3 and 6 of treatment than in the SHR-controls. Blood pressure in WKY rats was not affected by nicotine. Plasma and liver iron concentrations in the nicotine-treated SHR were higher than the SHR-controls and the WKY groups. Nicotine treatment did not affect plasma and liver zinc and copper concentrations or liver manganese (Mn) concentrations. Plasma ceruloplasmin activity was increased by nicotine treatment in the SHRs. Liver Mn superoxide dismutase (MnSOD) activities and glutathione concentrations, and liver and heart glutathione reductase activities, were higher in both groups of SHRs than in the WKY groups. Red cell SOD activity in the nicotine-treated SHR was lower than in the SHR-controls. In summary, blood pressure increased more rapidly in the nicotine-treated SHRs compared to the controls. The marked effects on antioxidant status observed were attributable more to hypertension than to the nicotine treatment.
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PMID:Comparative effects of 6-week nicotine treatment on blood pressure and components of the antioxidant system in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. 774 May 54

Pretreatment of the gerbil brain with a 2-min period of sublethal ischemia protects against neuronal damage following a subsequent 3-min period of ischemia, which normally destroys pyramidal neurons in the CA1 region of the hippocampus. To clarify the role of superoxide dismutase (SOD) in this ischemic tolerance, we immunohistochemically investigated the alterations in copper-zinc SOD (CuZnSOD) and manganese SOD (Mn-SOD) in the gerbil hippocampus following 3-min ischemia with or without the first mild ischemia. Normal hippocampus showed an intense CuZnSOD immunostaining in pyramidal neurons but relatively less MnSOD immunostaining. MnSOD, but not CuZnSOD, immunoreactivity increased after the first ischemia. Both CuZnSOD and MnSOD immunoreactivities decreased throughout the hippocampus 4 h after 3 min of ischemia both with and without the first ischemia. The immunostaining recovered in resistant regions (CA3 and dentate gyrus) after 1 day in both groups and in the pretreated CA1 after 2 days. Without pretreatment, however, the immunostaining never recovered in the vulnerable CA1 region. The results suggest that ischemic tolerance is induced in part by enhanced synthesis of MnSOD in the tolerance-acquired hippocampus. Both CuZnSOD and MnSOD immunoreactivities decreased after the second ischemia even in the pretreated hippocampus in the early reperfusion periods, but ischemic tolerance facilitated the recovery from the postischemic reductions in SOD immunoreactivity.
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PMID:Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance. 779 39

We have reported that members of the bcl-2 gene family are expressed and gonadotropin regulated in ovarian granulosa cells during follicular maturation and atresia. Because Bcl-2, a protein that prevents apoptosis in several cell types, is reported to function as an antioxidant or free radical scavenger, the present studies were designed to investigate if oxidative stress plays a role in granulosa cell apoptosis during follicular atresia in the immature rat ovary. In the first series of experiments, the role of oxidative stress in the induction of granulosa cell apoptosis was directly tested using a defined in vitro follicle culture system. Healthy antral follicles obtained from equine CG (eCG)-primed immature (27 day old) rats were incubated in serum-free medium for 24 h in the absence or presence of FSH (100 ng/ml; a control for inhibiting apoptosis), superoxide dismutase (SOD; 10-1000 U/ml), ascorbic acid (0.01-1 mM; a free radical scavenger), N-acetyl-L-cysteine (25-100 mM; a free radical scavenger and stimulator of endogenous glutathione peroxidase activity), or catalase (10-1000 U/ml). Granulosa cells within follicles incubated in medium alone exhibited extensive apoptosis after 24 h of incubation, and this onset of apoptosis was blocked by treatment with FSH (29 +/- 4% of controls; P < 0.001, n = 3). Moreover, apoptosis in follicles was also inhibited by treatment with SOD (44 +/- 4% of controls at 1000 U/ml; P < 0.01, n = 3), ascorbic acid (55 +/- 9% of controls at 1 mM; P < 0.05, n = 3), N-acetyl-L-cysteine (24 +/- 7% of controls at 100 mM; P < 0.001, n = 3), or catalase (35 +/- 6% of controls at 1000 U/ml; P < 0.001, n = 3). In the second series of experiments, complementary DNAs corresponding to secreted (SEC-SOD), copper/zinc-containing (Cu/Zn-SOD), and manganese-containing (Mn-SOD) forms of rat SOD, rat seleno-cysteine glutathione peroxidase (GSHPx), and rat catalase were isolated and used to synthesize antisense RNA probes for Northern and slot blot analysis of changes in SOD, GSHPx, and catalase gene expression during follicular maturation. In vivo priming of 25-day-old female rats for 2 days with 10 IU eCG, which promoted antral follicular growth and survival, increased levels of messenger RNA encoding SEC-SOD (216 +/- 9% of saline-treated controls, P < 0.05, n = 3) and Mn-SOD (222 +/- 14% of saline-treated controls, P < 0.05, n = 3) vs. saline-treated controls.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibitors of oxidative stress mimic the ability of follicle-stimulating hormone to suppress apoptosis in cultured rat ovarian follicles. 782 37

Because superoxide (O2-.) is a mediator of inflammation, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) has been employed as an anti-inflammatory compound. However, Cu,Zn-SOD can increase intra- and extracellular H2O2. This may react with the Cu atom of SOD in a Fenton-type reaction producing the hydroxyl radical (.OH). With a non-physiological concentration of H2O2 (0.8 mmol/l) to stimulate chemiluminescence (CL) at a level < 2 mV, it was observed that the addition of Cu,Zn-SOD (100 micrograms/ml) yielded an increase of 204.7 +/- 78.2 mV (P < 0.05). This increase in CL depended on the concentrations of H2O2 and Cu,Zn-SOD and was only seen with luminol (reacts with O2-. and .OH) but not with lucigenin (reacts with O2-.). No CL was observed when Cu,Zn-SOD was heat inactivated, or when Mn-SOD was used. Dissipators of H2O2, copper chelators and .OH scavengers attenuated this CL. In electron paramagnetic resonance, with the use of the spin-trap dimethylpyrroline-N-oxide (DMPO), it was demonstrated that, in the reaction between H2O2 and Cu,Zn-SOD, .OH was generated. The oxidation of keto-methylthiobutyric acid (KMB) to ethylene, assessed by gas chromatography, demonstrated that H2O2/Cu,Zn-SOD-generated .OH can react with KMB and not only with the SOD molecule itself. We conclude that H2O2 reduces SOD-bound Cu2+ to Cu1+ which, in reaction with H2O2 catalyses its reduction to OH. Whether this 'pro-inflammatory' reaction occurs in vivo remains to be established.
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PMID:Copper, zinc-superoxide dismutase and hydrogen peroxide: a hydroxyl radical generating system. 785 Sep 93

1. Control and copper-deficient rats were treated with: (i) indomethacin; (ii) indomethacin in the presence of cimetidine; and (iii) indomethacin in the presence of Cu(cimetidine)2. The levels of copper, zinc and manganese as well as the nature of superoxide dismutase activity in the liver were studied. 2. Copper deficiency caused a decrease of enzyme SOD activity, EDTA-insensitive (by 84%) and the appearance of nonenzyme SOD-like activity, EDTA-sensitive. The levels of copper and zinc decreased by 67% and 40% and the manganese level increased by 53%. 3. The above-mentioned treatments (i, ii, iii) of copper-deficient rats induced a progressive increase of enzyme SOD activity (by 19, 90 and 176%, respectively) without, however, changing nonenzyme SOD-like activity. It was only indomethacin treatment in the presence of Cu(cimetidine)2 that increased the copper level in control (by 82%) and copper-deficient (by 182%) rats. 4. The liver contained 4 CuZnSOD- and 1 MnSOD-isoenzymes, whose number and position on the gel were affected neither by copper deficiency nor by indomethacin treatment in the presence of Cu(cimetidine)2. Copper deficiency significantly increased the MnSOD-band and reduced the CuZnSOD-bands, particularly that with pI approximately 5.7. Indomethacin in the presence of Cu(cimetidine)2 changed neither the MnSOD-band nor the reduced CuZnSOD-band with pI approximately 5.7, but restored to normal all the other CuZnSOD-bands.
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PMID:Do indomethacin and cimetidine or Cu(cimetadine)2 affect the nature of superoxide dismutase activity in the liver of copper-deficient rats? 795 24

To investigate the involvement of oxygen radicals in the development of asthma, we examined the time course of changes in the expression of superoxide dismutases (SODs) both at mRNA and protein levels in the rat model of allergic asthma. We then examined the effects of recombinant-human SOD (r-hSOD) on these expressions and on the late asthmatic response (LAR). 1) In situ hybridization histochemistry and immunocytochemistry revealed that non-sensitized and sensitized rats before challenge had a very low level of manganese SOD (MnDOS) in the bronchial epithelial cells, although they showed a significant level of copper-zinc SOD (CuZnSOD). 2) All of the animals displayed LAR within 7 hours after the challenge, when they showed dramatic induction of MnSOD, but not of CuZnSOD, in the epithelial cells. 3) Treatment with r-hSOD almost completely suppressed LAR, with abolishment of MnSOD induction. This study suggests that the oxygen radical plays an important role in the inflammatory state of bronchial asthma, during which some cytokines induce the expression of MnSOD in the lung.
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PMID:[Superoxide dismutase suppressed asthmatic response with inhibition of manganese superoxide induction in rat lung]. 800 57

Oxidants are ubiquitous in our aerobic environment and could play an etiological role in aging and neurodegenerative diseases such as Alzheimer's disease. All cells contain several antioxidant enzymes, most importantly, superoxide dismutases (MnSOD and CuZnSOD), glutathione peroxidase (GSH-Px), glutathione reductase and catalase. The individual contribution of these antioxidant enzymes in neuronal protection during aging and under in vivo conditions remains unknown. We feel that the use of genetic manipulations to construct cells and/or transgenic mice that specifically overexpress or lack a single function represent a way to an understanding of the role of the individual antioxidant enzymes in neuronal aging. Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all tissues of Down syndrome (DS) patients. It has been suggested that this increment, by accelerating hydrogen peroxide formation, might promote oxidative damage within DS cells and might be involved in the various neurobiological abnormalities found in DS such as premature aging and Alzheimer-type neurological lesions. Moreover, the level of CuZnSOD protein and mRNA is particularly high in pyramidal hippocampal neurons susceptible to degenerative processes in Alzheimer's disease, and in dopaminergic melanized-neurons vulnerable in Parkinson's disease. In order to test this hypothesis, we have created transfected cells and transgenic mice which express human CuZnSOD gene. An oversupply of this enzyme is not beneficial to the brain of transgenic mice and causes increased thiobarbituric-reactive substances (TBARS), an index of lipid peroxidation, and may be due to peroxides generated by an imbalance between enzymatic activities of CuZnSOD and GSH-Px. Unlike what has been observed in transfected cells with the human CuZnSOD gene, but similar to what was found in the DS fetal brain, the GSH-Px activity was not increased in the brain of transgenic mice. One possibility to explain this discrepancy could be the differential cellular localization of these two enzymes in the brain (CuZnSOD in neurons and GSH-Px in glial cells). This heterogeneous cellular distribution of the enzymes implicated in oxygen-free radicals detoxification could participate to a selective neuronal degeneration. Interestingly, overexpression of CuZnSOD in the brain of transgenic mice is associated with an increased MnSOD activity, the mitochondrial form of the enzyme. This increased MnSOD might be a defense response to protect mitochondria from oxidative damage.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Transgenic mice overexpressing copper-zinc superoxide dismutase: a model for the study of radical mechanisms and aging]. 801 10

The effects of dietary copper deprivation on the activities, immunoreactive protein concentrations, and mRNA abundance of copper/zinc- and manganese-superoxide dismutase (Cu/Zn- and Mn-SOD) were examined in liver, heart, and brain of weanling rats fed a Cu-deficient diet for 4 weeks. Hepatic Cu/Zn-SOD activity, enzyme content, and mRNA abundance were significantly reduced, and, conversely, the activity, protein, and mRNA levels of Mn-SOD were significantly elevated in Cu-deficient rats. In Cu-deficient heart, the activity and protein content for Cu/Zn-SOD were reduced, whereas those for Mn-SOD were increased; the levels of mRNAs for these two enzymes was unaffected. Dietary Cu deficiency was without effect on the activities, enzyme contents, and mRNA abundance of brain Cu/Zn- and Mn-SOD. These results indicate that SODs from liver, heart, and brain exhibit differential sensitivities to dietary Cu deprivation, and that different mechanisms (transcriptional, posttranscriptional, or posttranslational) may be involved in their regulation.
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PMID:Differential regulation of superoxide dismutase in copper-deficient rat organs. 802 4

Copper deficiency in rats resulted in a decrease of liver cytosolic and lysosomal CuZnSOD activity (by 71% and by 55%, respectively) and in an increase of mitochondrial MnSOD (by 185%). The content of copper and zinc decreased by 64% and 38%, respectively, and that of manganese increased by 47%. Cytosolic CuZnSOD activity, both in control and copper-deficient rats, increased (by 71.5 units/mg protein and by 83.0 units/mg protein, respectively) after indomethacin treatment. Rat liver contained four CuZnSOD (cytosolic and lysosomal) and one MnSOD isoenzyme. Neither copper deficiency nor indomethacin treatment changed the position and the number of bands. The CuZnSOD-band with pI approximately 5.7 was greatly decreased by copper deficiency and was not restored to normal after indomethacin treatment.
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PMID:Liver superoxide dismutases after copper deficiency and/or indomethacin treatment of rats. 806 49

Changes in zinc (Zn) metabolism and interleukin-1 beta (IL-1 beta) release occur as part of the physiological response to tissue injury and trauma. In the present study, the influence of Zn status on the response to continuous low-dose IL-1 beta administration was evaluated. Rats were fed 50 micrograms Zn/g (adequate zinc; AZn) or 5 micrograms Zn/g (marginal zinc; MZn) diets for 14 days. On day 15, rats were infused via osmotic minipumps, with IL-1 beta (2.3 ng/hr) or saline (control, C) and euthanized 1, 3, or 7 days later. In the AZn rats, IL-1 beta infusion resulted in increased plasma copper (Cu) concentrations and ceruloplasmin (Cp) activity, and decreased iron (Fe) concentrations throughout the 7d period. These effects were most pronounced on d1 and d3. A similar trend was observed in the MZn rats, but IL-1 beta-induced increases in plasma Cu and Cp activity were less than in the AZn fed rats. In MZn and AZn IL-1 beta infused rats, plasma Zn was decreased on Day 1, and Day 3, respectively, compared with their respective controls. AZn IL-1 beta-infused rats were characterized by high liver Fe, Zn, and metallothionein (MT) concentrations on Day 1; by Day 7, only MT concentrations remained elevated. Liver MnSOD activity was 13%-29% higher in both the AZn- and MZn-IL-1 beta-infused rats than their respective controls on Day 3 and Day 7, with most significant increase observed on Day 7. These data show that Zn status can influence the response to low-dose IL-1 beta; this influence of Zn should be considered when IL-1 beta is given therapeutically.
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PMID:Zinc status and interleukin-1 beta-induced alterations in mineral metabolism in rats. 807 54


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