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)

A correlation between the changes in the rates of superoxide radical generation, upsilon, in microsomes, mitochondria, and nuclei and the Cu, Zn- and Mn-SOD activities in rat liver during the first 5 days after partial hepatectomy, has been studied. Level of upsilon in microsomal and mitochondrial membranes in the regeneration process was reduced. The Cu, Zn- and Mn-SOD activities changed in an extreme and antibate manner: the former was characterized by a minimum, whereas the latter-by a maximum with an extreme on the 3rd day after surgery. Analysis of the correlation between the values of upsilon in the nuclear membranes and cell cycle stages (on a literary basis) revealed that the upsilon was decreased 2 times on the stage of DNA synthesis. When mitosis was at maximum, upsilon showed a 4-5-fold increase in comparison with the control, the Cu, Zn-SOD activity being essentially unchanged. A role of SOD and O2-. in cell division is postulated. O2-. is assumed to play a role in gene expression, disassembly, and regeneration of the nuclear membrane; that of SOD is thought to consist in regulation of the proliferative activity.
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PMID:[Formation of superoxide radicals in membranes of subcellular organelles in regenerating liver]. 132 94

An acute dose of ethanol was used to investigate the biochemical response of tissues with a compromised antioxidant defense system to a surge of oxygen radical production. The copper (Cu)-deficient rat served as the animal model for this study based on its compromised antioxidant defense system. Rats were fed control (10 micrograms Cu/g) or Cu-deficient (0.2 microgram Cu/g) diet for 14 days. In order to minimize secondary effects associated with chronic Cu deficiency, the chelator triethylenetetramine was added to the Cu-deficient diet to shorten the time required for the induction of Cu deficiency. On day 14, rats were gavaged with ethanol (4.5 g/kg b.wt.) or saline and killed 9 hours postgavage. Rats fed the Cu-deficient diets had lower liver superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities than controls. Ethanol treatment had no effect on liver CuZnSOD or Gpx activity, while MnSOD activity was higher than saline control levels following EtOH treatment. Despite low GPx and SOD activity, Cu-deficient rats did not exhibit higher hepatic thiobarbituric acid reacting substances (TBARS) than controls; in fact, hepatic microsomal TBARS were lower in saline-treated Cu-deficient rats relative to Cu-sufficient rats. Ethanol treatment resulted in higher whole homogenate and mitochondrial TBARS than in saline-gavaged rats. Copper status did not influence hepatic TBARS production in response to an acute EtOH load. These data suggest that compensatory mechanisms contribute to the protection of the liver from excessive free radical production in this model of Cu deficiency.
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PMID:Influence of copper status on the response to acute ethanol exposure in rats. 178 25

O2-generation rate (Vo2-) in microsomal, mitochondrial and nuclei liver membranes was measured by ESR method, by accumulation of stable nitroxide radicals. These Vo2- values were compared with Cu, ZnSOD and MnSOD activities after 2 hours ischemia and 24 hours reoxygenation. O2- radicals generated by electron transfer chains are concluded to damage mainly during the ischemia, but not the reoxygenation.
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PMID:[Membranes of subcellular organelles as the source of superoxide radicals in liver ischemia]. 239 90

A sensitive and reliable assay method was developed to characterize crude cell homogenates and subcellular fractions with regard to their superoxide dismutase (SOD) activities. The determination of SOD activities was based on the well-known spectrophotometric assay introduced by McCord & Fridovich [(1969) J. Biol. Chem. 244, 6049-6055], with partially succinylated (3-carboxypropionylated) rather than native ferricytochrome c as indicating scavenger. Partial succinylation of cytochrome c resulted in minimization of interference associated with the interaction of cytochrome c with mitochondrial cytochrome c oxidase or cytochrome c reductases. The further increase in specificity, with regard to exclusion of cytochrome c oxidase interference, gained as a consequence of the high pH of 10 enabled the analysis of samples as rich in cytochrome c oxidase activity as the mitochondrial fraction in the presence or absence of membrane-disrupting detergents. Linear relationships for the dependence of the SOD activities with protein concentration were obtained with rat liver homogenate, mitochondrial and microsomal fractions, indicating negligible interference. Furthermore, by choosing a high pH for the assay medium, a 4-fold increase in sensitivity compared with the classical SOD assay, carried out at pH 7.8, was gained as well as a more precise resolution of Cu/Zn-SOD and Mn-SOD by 2 mM-KCN in samples with a high ratio of Mn-SOD to Cu/Zn-SOD, such as mitochondria. The complete trapping of the O2.- radicals, which was more feasible at pH 10 than at pH 7.8, enabled the application of a simple equation derived for the calculation of appropriately defined units of SOD activity from a single experiment.
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PMID:A spectrophotometric assay for superoxide dismutase activities in crude tissue fractions. 302 8

Fish (Sparus aurata) were intraperitoneally injected with model xenobiotics and several biomarkers of oxidative stress were analysed after 2 and 7 days exposure. The levels of soluble thiobarbituric acid reactive substances (TBARS) increased markedly in animals treated with polar xenobiotics, CuCl2 or paraquat; exposure to the apolar xenobiotics, dieldrin or malathion, enhanced significantly the microsomal TBARS while decreasing the microsomal glutathione transferase activity. The specific superoxide dismutase (SOD) activity increased in Cu(II)-injected animals but diminished in fish exposed to paraquat. After isoelectrofocusing separation and activity staining cell-free extracts of fish exposed to Cu(II), dieldrin or malathion displayed two new Cu,Zn-SOD isoforms of intermediate pI. An additional Mn-SOD was observed in dieldrin-injected fish, but only a faint new acidic isoform was observed in paraquat-injected animals. The new SOD bands were reproduced in vitro by incubation of cell-free extracts with systems generating superoxide anion or hydrogen peroxide and with a tert-butyl hydroperoxide/ADP-Fe system. Metallothionein induction was observed in Cu(II) or paraquat-exposed fish, but not in animals injected with apolar xenobiotics. So, the new SOD bands are possibly oxidized forms of this enzyme and can be considered as useful early biomarkers of oxidative stress due to transition metals or organic xenobiotics.
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PMID:Oxidative stress in fish exposed to model xenobiotics. Oxidatively modified forms of Cu,Zn-superoxide dismutase as potential biomarkers. 854 64

We demonstrated previously that dietary manganese (Mn) deficiency depressed Mn concentrations in most tissues and consistently depressed Mn superoxide dismutase (MnSOD) levels in heart. To examine the functional consequences of these effects, we fed weanling male Sprague-Dawley rats (n = 12/diet) diets containing 20% (wt/wt) corn oil or 19% menhaden oil + 1% corn oil by weight and 0.75 or 82 mg Mn/kg diet for 2 mo (the fish oil mixture was supplemented with (+)-(mixed)-alpha-tocopherol to the level in corn oil). Heart and liver Mn concentrations in the Mn-deficient rats were 56% of those in Mn-adequate rats (P < 0.0001), confirming Mn deficiency. The Mn-deficient rats had more conjugated dienes in heart mitochondria than Mn-adequate rats (P < 0.001); rats fed fish oil had more conjugated dienes than those fed corn oil (P < 0.001). The MnSOD activity was inversely correlated with conjugated dienes (r = -0.71, P < 0.005), and Mn-deficient rats had 37% less MnSOD activity in the heart than did Mn-adequate rats (P < 0.0001). The dietary treatments did not affect heart microsomal conjugated diene formation, possibly because of compensation by copper-zinc (CuZn) SOD activity; CuZnSOD activities were 35% greater in the hearts of Mn-deficient animals (P < 0.01). Liver was less sensitive to Mn deficiency than was the heart as judged by MnSOD activity and conjugated diene formation. This work is the first to demonstrate that dietary Mn protects against in vivo oxidation of heart mitochondrial membranes.
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PMID:Manganese protects against heart mitochondrial lipid peroxidation in rats fed high levels of polyunsaturated fatty acids. 855 11

The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p < 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p < 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.
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PMID:Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion. 940 79

The effects in fish (Sparus aurata) of dieldrin, previously reported to be an inducer of peroxisomal enzymes (Pedrajas et al., Comp. Biochem. Physiol. 115C (1996) 125-131), were compared with those of clofibrate. Although dieldrin provoked the more severe peroxisomal changes, both compounds induced oxidative stress as detected by the increased levels of microsomal thiobarbituric acid reactive substances; however the malondialdehyde (MDA) content, determined after HPLC separation of the MDA-TBA complex, was not significantly altered. These results suggest that, besides MDA, other aldehydes were formed in xenobiotic-injected fish, leading us to assess the oxidative effects of such xenobiotics by following changes in superoxide dismutase (SOD) pattern. New active SOD isoforms were detected by isoelectrofocusing in the light mitochondrial (LMF) and cytosolic (CF) fractions. Most of the new SOD bands could be reproduced in vitro by incubation of fish liver cell-free extracts with MDA. To clarify the effects of aldehydes, Cu,Zn- and Mn-SOD isoforms were purified and amino acid analysis was carried out. The new bands found in LMF and CF fractions were reproduced in vitro after incubation of pure SODs with MDA and 4-hydroxy-2-nonenal (HNE), the new SOD bands formed being coincident with the loss of Lys or His residues. Lysine residues were preferentially derivatized after treatment of Cu,Zn-SOD with MDA, but in Mn-SOD the lysine residues were modified only after treatment with MDA, while the histidine residues were modified only by HNE. No change of SOD activity was detected after MDA or HNE exposure, although at the higher aldehyde concentrations used protein aggregates were formed. Therefore, the appearance of new active SOD bands, after isoelectrofocusing separation, can be proposed as a biomarker of oxidative stress.
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PMID:Incubation of superoxide dismutase with malondialdehyde and 4-hydroxy-2-nonenal forms new active isoforms and adducts. An evaluation of xenobiotics in fish. 987 97

The stimulatory effect of iron and ascorbate on the damaging action of cyclosporine in kidney mitochondria, microsomes and epithelial cells was examined. Cyclosporine induced malondialdehyde formation and hydrogen peroxide production in mitochondria and attenuated the activity of MnSOD and glutathione peroxidase. The damaging effect of cyclosporine (50 microM) plus Fe2+(20 microM) on mitochondrial and microsomal lipids and proteins as well as mitochondrial thiols was greater than the summation of the oxidizing action of cyclosporine alone and Fe2+ alone. As for tissue components, iron enhanced cyclosporine-induced viability loss in kidney epithelial cells. Fe2+, EDTA and H2O2- induced 2-alpha deoxyribose degradation was attenuated by 10 mM DMSO and 200 microM DTPA but not affected by 200 microM cyclosporine. The addition of Fe2+ caused a change in the absorbance spectrum of cyclosporine in the wavelength range 230-350 nm. The simultaneous addition of cyclosporine (50 microM) and ascorbate (100 microM) showed the enhanced peroxidative effect on mitochondrial and microsomal lipids, which was inhibited by DTPA and EDTA (1 mM). Similar to iron, ascorbate enhanced cyclosporine-induced cell viability loss. The results show that iron and ascorbate promote the damaging action of cyclosporine in kidney cortex mitochondria and microsomes and in kidney epithelial cells, which may contribute to the enhancement of cyclosporine-induced nephrotoxicity.
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PMID:Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes. 1124 18

Activities of protective antioxidant enzymes, the rate of superoxide formation (v) in microsomal membranes and submitochondrial particles (SMP), and the concentrations of reduced and oxidized glutathione in cytosol were studied in the liver of AKR mice during the development of spontaneous leucosis. It was found that in the latent period of leucosis (mice of 3-6 months of age) the glutathione reductase (GR) activity in cytosol and mitochondria decreased and v in SMP increased. The increase in v in SMP did not result in the induction of Mn-SOD. In this stage of leucosis, the activities of Cu,Zn-SOD, GSH-Px, and G-6-PDH in cytosol were unchanged; at the same time, the GR activity and the concentration of reduced glutathione smoothly decreased. In the stage of developed leucosis (mice of 7-9 months of age), non-synchronous changes in the antioxidant system resulting in the shift of metabolism towards the prooxidant state were found. Comparison of our findings and the literature data demonstrates that the observed decrease in the SOD/GSH-Px ratio, the decrease in GR activity, and the increase in the v/Mn-SOD activity ratio are typical for pre-neoplastic changes in cell metabolism.
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PMID:Imbalance in the enzymatic system of production and consumption of active oxygen species in liver of AKR mice with spontaneous leucosis. 1156 51


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