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)

The transgenic mice overexpressing heat shock protein 72 (HSP72) or antioxidants have been reported to be more resistant to myocardial ischemia/reperfusion injury. However, it remains unknown whether whole body heat stress (HS) which may induce HSP72 or endogenous antioxidants affords similar protection in the mouse heart. Adult male mice were treated with either HS (42 degrees C for 15 min) or anesthesia only (SC) against a group of non-stressed controls (NC). At 6 or 24 h later, the hearts were excised and perfused at a constant pressure of 55 mmHg in Langendorff mode. Following 30 min equilibration, hearts were subjected to 20 min of global ischemia and 30 min reperfusion (37 degrees C). Ventricular force was measured by a force-displacement transducer attached to the apex. Leakage of intracellular enzymes (CK, LDH) was measured in coronary efflux. Infarct size was determined by tetrazolium staining. The results showed that no significant differences between HS, SC, and NC groups in ventricular contractile function, CK and LDH release, or infarct size were observed at either time window. HS enhanced the expression of HSP72 in mouse hearts by two- to three-fold, whereas antioxidant enzyme activities (catalase and MnSOD) did not change significantly. We conclude that HS does not precondition the isolated perfused mice hearts against ischemia/reperfusion injury, despite induction of HSP72.
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PMID:Whole body heat shock fails to protect mouse heart against ischemia/reperfusion injury: role of 72 kDa heat shock protein and antioxidant enzymes. 992 59

The role of Cu/Zn-superoxide dismutase (SOD) in myocardial ischemic reperfusion injury was studied by using a mouse model with targeted disruption of the mouse Sod I gene. Inactivation of the functional mouse Sod I gene in hearts by gene targeting (Sod I(+/-)) resulted in a 50% reduction of Cu/Zn-SOD mRNA and significant reduction of Cu/Zn-SOD enzyme activity compared with that of wild-type Sod I(+/+) mice. Cu/Zn-SOD mRNA could not be detected in Sod I(-/-) heart. The isolated buffer-perfused hearts from the knockout mice devoid of any functional copy of the Sod I (Sod I(-/-)) and matched nontransgenic control mice were subjected to 30 minutes of global ischemia followed by 2 hours of reperfusion. For both groups of mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the Sod I(-/-) was less compared with the wild-type mice. Thus, the postischemic recovery of the developed force and the maximum first derivative of the developed force were consistently lower for the Sod I(-/-) mouse hearts compared with wild-type control hearts. The coronary flow was lower compared with the baseline levels for both groups of hearts, but there was no significant difference between the groups. The myocardial infarction determined from the ratio of infarct size/area of risk was higher for the Sod I(-/-) mice compared with the control mice. The amount of creatine kinase release from the wild-type mouse hearts was less compared with the Sod I(-/-) mouse hearts. In concert, a reduced amount of oxidative stress was found in the hearts of wild-type mice compared with Sod I(-/-) mouse hearts. These results documented that Sod I(-/-) mouse hearts were more susceptible to ischemic reperfusion injury compared with corresponding wild-type mouse hearts, suggesting that the Sod I gene constitutes an important defense element for the hearts.
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PMID:Targeted disruption of the mouse Sod I gene makes the hearts vulnerable to ischemic reperfusion injury. 1067 76

Reactive oxygen species (ROS; O2-, H2O2, and OH), normal by-products of cellular metabolic processes, are kept in control by antioxidant enzymes, such as catalase, glutathione peroxidase (GPX) and superoxide dismutases (SODs). To understand the role of antioxidant enzymatic defenses against ROS injury following ischemia-reperfusion, we examined the effect on kidney exposed to varying periods (30, 60 or 90 min) of ischemia followed by different periods of reperfusion. The enzymatic activities and protein levels of catalase, GPX, CuZnSOD and MnSOD were relatively unaffected at 30 min of ischemia followed by 0, 2 or 24 h reperfusion. However, 60 or 90 min of ischemia followed by 0, 2 or 24 h of reperfusion resulted in a decrease in activities and protein levels which paralleled the duration of ischemic injury. MnSOD activity tended to recover towards normal during reperfusion. Examination of the mRNA levels of these antioxidant enzymes demonstrated a severe decrease in mRNA levels of catalase and GPX at a time point of minimal ischemic injury (30 min of ischemia followed by reperfusion) suggesting that loss of mRNA of catalase and GPX may be the first markers of alterations in cellular redox in ischemia-reperfusion injury. Greater loss of mRNA for catalase, GPX and CuZnSOD was observed following longer periods (60 or 90 min) of ischemia. The mRNA for MnSOD was upregulated at all time points of ischemia-reperfusion injury. Actually, the greater decrease in mRNAs for catalase, GPX and CuZnSOD in the acute phase (within 24 h) subsequently showed a further decrease in these enzyme activities in the subacute phase (72 or 120 h after ischemia). These enzyme activities in the 30 min ischemia group, (but not in the 90 min group), already showed tendencies for normalization at 120 h after ischemia. To understand the molecular basis of the loss of mRNA of these antioxidant enzymes during ischemia-reperfusion injury, we examined the rate of transcription by nuclear run-on assays. The similar rates of transcription in control and kidney exposed to ischemia-reperfusion indicates that the loss of mRNA for catalase, GPX and CuZnSOD is possibly due to the increased rate of turnover of their mRNAs. These studies suggest that expression of antioxidant genes during ischemia-reperfusion are not coordinately expressed and that the differential loss of antioxidant enzymes may be the contributing factor(s) towards the heterogeneous renal tissue damage as a result of ischemia-reperfusion induced oxidative stress.
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PMID:Kidney ischemia-reperfusion: modulation of antioxidant defenses. 1082 17

Little is known concerning the effect of oxidative stress on the expression of antioxidative enzymes in the decompensated cardiac hypertrophy of spontaneously hypertensive rats (SHR), considered as a model of dilative cardiomyopathy in man. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) were characterized in isolated perfused hearts of 18 month old SHR and the age-matched normotensive control Wistar-Kyoto (WKY) rats, before and after 30 min infusion of 25 microM H(2)O(2). After infusion of H(2)O(2), aortic flow decreased in WKY from 26.2 +/- 2.2 to 16.0 +/- 0.8 ml/min (p <.05) but not in SHR (18.2 +/- 1.9 vs. 20.7 +/- 2.2 ml/min). This protection was related to the higher myocardial activities of GPx, MnSOD and CuZnSOD in SHR, compared with those of the WKY group. Although total SOD activity in the SHR fell after H(2)O(2) exposure (to 1.81 +/- 0.13 from 3.56 +/- 0.49 U/mg of protein), catalase activity increased (to 2.46 +/- 0.34 from 1.56 +/- 0.29 k min(-1)mg(-1)protein), compared with the pre-infusion period (p <.05 in each case). In additional studies, hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The results obtained in ischemic/reperfused hearts show the same changes in enzyme activities measured as it was observed in H(2)O(2) perfused hearts, indicating that oxidative stress is independent of the way it was induced. The higher catalase activity derived from elevated mRNA synthesis. The antioxidative system in dilative cardiomyopathic hearts of SHR is induced, probably due to episodes of oxidative stress, during the process of decompensation. This conditioning of the antioxidative potential may help overcome acute stress situations caused by reactive oxygen species in the failing myocardium.
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PMID:Effects of oxidative stress on the expression of antioxidative defense enzymes in spontaneously hypertensive rat hearts. 1103 13

Acute damage following ischemia and reperfusion (I/R) in the liver is in part caused by the generation of reactive oxygen species, such as superoxides, during the reperfusion event. Gene therapy directed at attenuating mitochondrial superoxide production following warm I/R injury in the liver has demonstrated great promise in reducing acute hepatocellular damage. In the present study, we have compared the therapeutic effects of ectopic expression of mitochondrial (MnSOD) and cytoplasmic (Cu/ZnSOD) superoxide dismutase using recombinant adenoviral vectors for reducing I/R damage in the liver. Consistent with previous observations, recombinant adenoviral delivery of MnSOD to the liver significantly attenuated both acute liver damage and AP-1 activation following I/R injury to the livers of mice. However, ectopic expression of Cu/ZnSOD diminished neither I/R-induced elevations in serum alanine transaminase (ALT) nor AP-1 activation. Interestingly, baseline activation of AP-1 before I/R-induced injury was seen in livers infected with recombinant Ad.Cu/ZnSOD, but not Ad.MnSOD or Ad.LacZ, vectors. The level of Cu/ZnSOD-induced AP-1 activation was significantly reduced by ablation of Kupffer cells or by coexpression of catalase, suggesting that increased H(2)O(2) production facilitated by Cu/ZnSOD in hepatocytes and/or Kupffer cells may be responsible for AP-1 activation. In vitro reconstitution studies using hepatocyte and macrophage cell lines demonstrated that Cu/ZnSOD overexpression induces AP-1 in both cell types, and that secretion of a Cu/ZnSOD-induced macrophage factor is capable of elevating AP-1 in hepatocytes. In summary, our findings demonstrate that subcellular sites of superoxide production in the liver can differentially affect the outcome of I/R injury in the liver and selectively influence AP-1 activation.
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PMID:Subcellular site of superoxide dismutase expression differentially controls AP-1 activity and injury in mouse liver following ischemia/reperfusion. 1128 55

The efficacy of glutathione (GSH) in protecting ischaemia-reperfusion (I-R) induced cardiac dysfunction and myocardial oxidative stress was studied in open-chest, stunned rat heart model. Female Sprague-Dawley rats were randomly divided into three experimental groups: (1) GSH-depletion, by injection of buthionine sulphoxamine (BSO, 4 mmol kg(-1), i.p.) 24 h prior to I-R, (2) BSO injection (4 mmol kg(-1), i.p.) in conjunction with acivicin (AT125, 0.05 mmol kg(-1), i.v.) infusion 1 h prior to I-R, and (3) control (C), receiving saline treatment. Each group was further divided into I-R, with surgical occlusion of the main left coronary artery (LCA) for 30 min followed by 20 min reperfusion, and sham. Myocardial GSH content and GSH : glutathione disulphide (GSSG) ratio were decreased by approximately 50% (P < 0.01) in both BSO and BSO + AT125 vs. C. Ischaemia-reperfusion suppressed GSH in both left and right ventricles of C (P < 0.01) and left ventricles of BSO and BSO + AT125 (P < 0.05). Contractility (+dP/dt and -dP/dt) in C heart decreased 55% (P < 0.01) after I and recovered 90% after I-R, whereas +/-dP/dt in BSO decreased 57% (P < 0.01) with ischaemia and recovered 76 and 84% (P < 0.05), respectively, after I-R. For BSO + AT125, +/-dP/dt were 64 and 76% (P < 0.01) lower after ischaemia, and recovered only 67 and 61% (P < 0.01) after I-R. Left ventricular systolic pressure in C, BSO and BSO + AT125 reached 95 (P > 0.05) 87 and 82% (P < 0.05) of their respective sham values after I-R. Rate-pressure double product was 11% (P > 0.05) and 25% (P < 0.05) lower in BSO and BSO + AT125, compared with Saline, respectively. BSO and BSO + AT125 rats demonstrated significantly lower liver GSH and heart Mn superoxide dismutase activity than C rats after I-R. These data indicate that GSH depletion by inhibition of its synthesis and transport can exacerbate cardiac dysfunction inflicted by in vivo I-R. Part of the aetiology may involve impaired myocardial antioxidant defenses and whole-body GSH homeostasis.
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PMID:Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stress. 1143 34

To clarify the mechanism of ischemic tolerance induced by HBO, we investigated the effect of HBO on immunoreactivity to Bcl-2 and Bax, apoptosis-regulating protein, or Mn-SOD, a radical scavenging system, in the CA1 sector of the gerbil hippocampus. Pretreatment comprising, five sessions at 2 ATA (atmosphere absolute) every other day, but not that comprising, ten sessions at 3 ATA every day, caused significant increases in Bcl-2 and Mn-SOD immunoreactivity in the CA1 sector compared with in the sham pretreatment group. No significant differences in Bax immunoreactivity and neuronal density in the CA1 hippocampal neurons was observed between the groups. These results suggest that protection against mitochondrial alterations after ischemia through Mn-SOD and/or Bcl-2 expression is related to the ischemic tolerance induced by repeated HBO pre-treatment.
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PMID:Mn-SOD and Bcl-2 expression after repeated hyperbaric oxygenation. 1145 26

We have characterized the temporal changes in iNOS, MnSOD and nitrotyrosine immune reactivity in a rat model of permanent middle cerebral artery occlusion under acute hyperglycemic or normoglycemic conditions followed by either 3- or 24-h recovery. We found that the macroscopic labeling pattern for all three antibodies colocalized with the ischemic core and penumbra which was determined by cresyl violet histological evaluation in adjacent sections. Hyperglycemia induced prior to ischemia resulted in earlier infarction which correlated with increased immunoreactivity for iNOS, MnSOD and nitrotyrosine. In the penumbral region of the frontal cortex, labeling of specific cell structures was largely limited to cortical neurons near the corpus callosum and was apparent earlier in the hyperglycemic rats. Increased polymorphonuclear leukocyte adhesion in blood vessels was observed at 24 h in the hyperglycemic group. At both of the recovery times studied, we observed only minor vascular staining for nitrotyrosine and none for iNOS. Our results are consistent with hyperglycemia resulting in an early and concomitant increase in both superoxide and nitric oxide production which can lead to peroxynitrite formation that then nitrates tyrosine residues. It would appear that hyperglycemic ischemia contributes to the early induction of key enzymes involved in nitric oxide bioavailability.
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PMID:Immunohistochemical detection of inducible nitric oxide synthase, nitrotyrosine and manganese superoxide dismutase following hyperglycemic focal cerebral ischemia. 1168 37

Previous studies have demonstrated that preconditioning the brain with cortical spreading depression (CSD) induces tolerance to a subsequent episode of ischemia. In other models of preconditioning, induction of ischemic tolerance has been associated with increased expression of the antioxidant enzyme, superoxide dismutase (SOD). The objective of the present study was to determine whether CSD upregulates Cu/Zn-SOD or Mn-SOD. CSD was induced in one hemisphere by applying 2 M KCl to the frontal cortex in Wistar rats. After 2 or 24 h of recovery, Cu/Zn-SOD and Mn-SOD mRNA levels were determined in both hemispheres using Northern blot analysis. In separate rats, Cu/Zn-SOD and Mn-SOD protein levels were determined 24 and 72 h after CSD using Western blot analysis. In addition, total SOD, Cu/Zn-SOD and Mn-SOD enzymatic activities were measured 24 and 72 h after CSD using spectrophotometric and zymographic assays. At the times investigated, no significant differences in mRNA or protein levels for Cu/Zn-SOD or Mn-SOD were observed between the ipsilateral and contralateral cortex. Further, there were no significant differences in Cu/Zn-SOD or Mn-SOD enzymatic activities between the two hemispheres at 24 or 72 h after CSD. In addition, CSD did not alter the activities of Cu/Zn-SOD or Mn-SOD in either hemisphere, relative to those in unoperated animals. Taken together, these results fail to support the hypothesis that CSD-induced tolerance is mediated through the upregulation of Cu/Zn-SOD or Mn-SOD.
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PMID:Preconditioning with cortical spreading depression does not upregulate Cu/Zn-SOD or Mn-SOD in the cerebral cortex of rats. 1173 Oct 8

The purpose of this study was to investigate the effectiveness of superoxide dismutase (SOD) overexpression in an acute model of hepatic oxidative stress. Oxidative stress was established using a warm ischemia-reperfusion model, where nearly 70% of the liver was made hypoxic by clamping the hepatic artery and a branch of the portal vein for 1 hr followed by restoration of blood flow. Animals were infected i.v. with 1 x 10(9) plaque-forming units (PFU) of adenovirus containing the transgene for cytosolic Cu/Zn-SOD (Ad.SOD1), mitochondrial Mn-SOD (Ad.SOD2), extracellular Cu/Zn-SOD (Ad.SOD3), or the bacterial reporter gene for beta-galactosidase (Ad.lacZ) 3 days prior to experiments. Ad.SOD1 and Ad.SOD2 caused a three-fold increase in SOD expression and activity in liver compared to Ad.lacZ-treated control animals. Intravenous administration of Ad.SOD3 increased SOD activity slightly in serum but not in liver. Increases in serum transaminases and pathology due to ischemia-reperfusion were blunted by Ad.SOD1 and Ad.SOD2; however, extracellular SOD had no significant effect. Moreover, lipid-derived free radical adducts (a(N) = 15.65 G and a(H)(beta) = 2.78 G) were increased by ischemia-reperfusion. This effect was blunted by about 60% in Ad.SOD1- and Ad.SOD2-infected animals, but was unaffected by Ad.SOD3. However, when high doses of Ad.SOD3 (3 x 10(10) PFU) were administered. serum SOD activity was elevated three-fold and was protective against hepatic ischemia-reperfusion injury under these conditions. These data demonstrate that adenoviral delivery of superoxide dismutase can effectively reduce hepatic oxidative stress.
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PMID:Comparison of the effect of adenoviral delivery of three superoxide dismutase genes against hepatic ischemia-reperfusion injury. 1177 1


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