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)

Brain injury in Mongolian gerbil (Merisones unguiculatus) was induced by occluding bilateral common carotid arteries for 60 min followed by reperfusion for 5 or 30 min. Oxygen free radicals in brain tissue were measured by electron spin resonance (ESR) technique, malondialdehyde (MDA) was measured by fluorescence spectrometry, and superoxide dismutase (SOD) was measured by nitrite kit. Oxygen free radicals and MDA were not significantly increased, but activities of T-SOD and Mn-SOD were decreased after 60 min of cerebral ischemia. The free radicals were increased at 5-min reperfusion, and then reduced to the level of ischemia group after 30-min reperfusion. MDA was increased remarkably after reperfusion of 30 min, whereas the activity of SOD continued to decrease. Sodium diethyldithiocarbamate (DTC), i.v. 5-100 mg.kg-1 15 min before occlusion, decreased the production of MDA and increased the activities of T-SOD and Mn-SOD. The formation of oxygen free radicals was depressed by i.v. DTC 50 mg.kg-1. The result suggested that the protective effects of DTC on ischemia-reperfusion-induced brain injury might be induced by scavenging the oxygen free radicals, increasing the Mn-SOD activity and decreasing the production of MDA.
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PMID:[Effects of sodium diethyldithiocarbamate on ischemia-reperfusion-induced brain injury in Mongolian gerbil]. 771 79

This study investigated the possibility that hyperglycemia induces early expression of various superoxide dismutases (SOD) and nitric oxide synthases (NOS) following focal cerebral ischemia in the rat. MnSOD, CuZnSOD, nNOS and eNOS mRNA and protein expression were examined 3 h after permanent middle cerebral artery occlusion under acute hyperglycemic or normoglycemic conditions. 2,3,5-triphenyltetrazolium chloride (TTC) treatment post-mortem revealed a significant area at risk of infarction following ischemia in hyperglycemic compared to normoglycemic rats. Although no changes in MnSOD, CuZnSOD, nNOS and eNOS mRNA expression were detected, Western blots of ischemic cortex revealed an increase in MnSOD and CuZnSOD protein expression in hyperglycemic compared to normoglycemic rats. Pre-treatment of hyperglycemic rats with the NOS inhibitors L-nitroarginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) or dehydroascorbic acid (DHA), a superoxide scavenger, significantly reduced the TTC delineated zone. The hyperglycemia-induced post-transcriptional upregulation of MnSOD and CuZnSOD levels suggest a response to increased superoxide production which, in the presence of increased nitric oxide production, may play a major role in the increased risk of damage following hyperglycemic stroke.
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PMID:Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat. 1538 Jun 26

The purpose of this study was to investigate the role of superoxide dismutase (SOD) and catalase (CAT) in brain ischemic tolerance induced by ischemic preconditioning. Forebrain cerebral ischemia was induced in rat by four vessel occlusion. The activities of the antioxidant enzymes CuZn-SOD, Mn-SOD and CAT were measured in the hippocampus, striatum and cortex after 5 min of ischemia used as a preconditioning and subsequent reperfusion, by spectrophotometric methods. In all ischemia-reperfusion groups (5 h, 1 and 2 days of reperfusion), CuZn-SOD activities were found to be increased if compared to the sham operated controls. The increase was significant (P < 0.05) in all reperfusion groups, particularly after 5 h of reperfusion (3 times) in all studied brain regions; the largest increase was detected in the more vulnerable hippocampus and striatum. Very similar changes were found in Mn-SOD activity. The activity of CAT was increased too, but reached the peak of postischemic activity 24 h after ischemia. Our attempt to understand the mechanisms of increased SOD and CAT activities by application of protein synthesis inhibitor cycloheximide showed that this increase was caused by de novo synthesis of enzymes during first hours after ischemia. Our findings indicate that both major endogenous antioxidant enzymes SOD and CAT are synthesized as soon as 5 h after ischemia. In spite of significant upregulation of these enzymes a large number of neurons in selectively vulnerable CA1 region of hippocampus undergoes to neurodegeneration within 7 days after ischemia.
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PMID:Changes of endogenous antioxidant enzymes during ischemic tolerance acquisition. 1607 25

1. The aim of this work was to study potential mechanisms participating in postischemic protection of selectively vulnerable CA1 neurons in the hippocampus. Experiments were focused on measuring changes in endogenous antioxidant enzyme activity. 2. Forebrain cerebral ischemia was induced in a rat by four-vessel occlusion. Ten minutes of ischemia induces so-called delayed neuronal death in selectively vulnerable CA1 region 3 days later. After 7 days of reperfusion, 71.6% of neurons succumb to neurodegeneration. When 5 min of ischemia was used as postconditioning, 2 days after 10 min of cerebral ischemia, delayed neuronal death in CA1 was almost completely (89.9%) prevented. 3. Searching for mechanisms of protection, we measured the activity of endogenous antioxidant enzymes. Activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were measured in the hippocampus, striatum and cortex by spectrophotometric methods after 10 min of ischemia used as the preconditioning. Two days after the preconditioning or the sham operation, second ischemia was induced for 5 min. We observed significant increase of total SOD activity in all studied regions of the brain 5 h after postconditioning (5 min of ischemia). SOD activity decreased to control values after 24 h. 4. In some experiments, we used intraperitoneal injections of norepinephrine (3.1 microM/kg) or 3-nitropropionic acid (20 mg/kg) as postconditioning, instead of ischemia. All three treatments resulted in significant increase of SOD activity, but norepinephrine was the most effective. The same effect as was seen for total SOD activity could be observed for CuZn-SOD as well as Mn-SOD activity. Similarly, considerable increase in the activity of catalase was detected 5 h after postconditioning (5 min of ischemia). It is interesting that the greatest changes were established in selectively vulnerable hippocampus and striatum. As in the case of SOD, the highest levels of CAT activity were induced by norepinephrine, while lower but significant increase in CAT activity was induced by 3-nitropropionic acid.5. Our results suggest that endogenous antioxidants SOD and CAT could play considerable neuroprotective role after postconditioning.
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PMID:The changes in endogenous antioxidant enzyme activity after postconditioning. 1674 74

Early oxidative DNA damage is regarded to be an initiator of neuronal apoptotic cell death after cerebral ischemia. Although evidence suggests that HGF has the ability to protect cells from oxidative stress, it remains unclear as to how HGF suppresses oxidative DNA damage after cerebral ischemia. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) is a multifunctional protein in the DNA base repair pathway that is responsible for repairing apurinic/apyrimidinic sites in DNA after oxidation. We demonstrated that both the immunoreactivity and the number of APE/Ref-1-positive cells in the hippocampal CA1 region were decreased after transient forebrain ischemia and that treatment with HGF suppressed this reduction. The expression of Cu/ZnSOD and MnSOD in the hippocampal CA1 region did not change after ischemia, regardless of treatment with or not with HGF. The activity of NADPH oxidase was increased mainly in glia-like cells in the hippocampal CA1 region after ischemia, and this increase was attenuated by HGF treatment. These results suggest that the protective effects of HGF against cerebral ischemia-induced cell death in the hippocampal CA1 region are related to the improvement of neuronal APE/Ref-1 expression and the inhibition of NADPH oxidase activity in glia-like cells.
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PMID:The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. 1697 82

This study monitored the effects of sub-lethal ischemia (post-conditioning) applied after a previous ischemic attack by way of the MnSOD immune-reactivity examined in CA1 and dentate gyrus of the rat hippocampus. The experimental 10 min transient cerebral ischemia was followed by 2 days of reperfusion, the rats then underwent a second ischemia (4 or 6 min post-conditioning). MnSOD immune-reactivity was evaluated after 5 h, 1 and 2 days. Results obtained by computer microdensitometric image analysis indicated that 4 min of ischemic post-conditioning caused higher MnSOD immune-reactivity than 6 min. However, higher viability of CA1 neurons after stronger (6 min) post-conditioning when production of MnSOD is lower, as well as differences between MnSOD in CA1 and dentate gyrus indicates another mechanism switching pro-apoptotic destination of CA1 neurons to anti-apoptotic.
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PMID:Post-conditioning exacerbates the MnSOD immune-reactivity after experimental cerebral global ischemia and reperfusion in the rat brain hippocampus. 1793 46

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect neurodegenerative changes in two models of brain ischemia, photothrombotic cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in rodents. After systemic Mn(2+) injection to both ischemic models, a close pattern of T1-weighted hyperintensity was observed throughout different brain regions in comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby conventional MRI could hardly detect such. In addition, the infarct volumes in the posterior parts of the brain had significantly reduced after Mn(2+) injection to the MCAO model. It is suggested that exogenous Mn(2+) injection may provide enhanced MEMRI detection of oxidative stress and gliosis early after brain ischemia. Manganese may also mediate infarctions at remote brain regions in transient focal cerebral ischemia before delayed secondary damage takes place.
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PMID:Early detection of neurodegeneration in brain ischemia by manganese-enhanced MRI. 1916 61

Cumulative evidence demonstrates that apoptosis caused by oxidative stress plays a key role in neuronal cell death after transient focal cerebral ischemia. In this study, we investigated exactly the immunohistochemical alterations of neuronal nuclei (NeuN), Cu/Zn-SOD (superoxide dismutase), Mn-SOD, 4-hydroxy-2-nonenal (HNE), and single strand DNA (ssDNA) in the striatum from 3 h up to 15 days after transient focal cerebral ischemia in rats under the same conditions. A conspicuous decrease of NeuN immunoreactive neurons was observed in the ipsilateral striatum from 3 h up to 15 days after focal ischemia. For Cu/Zn-SOD, Mn-SOD and HNE immunostainings, the alteration of Cu/Zn-SOD and HNE immunoreactivity was more pronounced than that of Mn-SOD immunoreactivity in the shrunken or atrophic neurons of ipsilateral striatum 3 h after focal ischemia. Thereafter, a significant increase of HNE immunoreactivity was observed in the shrunken or atrophic neurons of ipsilateral striatum up to 15 days after focal ischemia. In contrast, a significant decrease of Cu/Zn-SOD immunoreactivity was found in the ipsilateral striatum from 3 up to 15 days after focal ischemia. On the other hand, a significant increase of Mn-SOD immunereactivity was observed in the ipsilateral striatum from 1 up to 7 days after focal ischemia. In addition, our Western blot analysis also showed a significant increase of Cu/Zn-SOD and Mn-SOD in the ipsilateral striatum 1 day after focal ischemia, as compared to sham-operated group. In contrast, a significant increase in the number of ssDNA immunoreactive apoptotic neurons was observed in the ipsilateral striatum from 3 h to 3 days after focal cerebral ischemia. The present results also suggest that increased reactive oxygen species (ROS) production during reperfusion may contribute to the induction of the alteration of lipid peroxidation and could thereby lead to apoptosis in neurons of the ipsilateral striatum after transient focal ischemia, because of an insufficient expression of Cu/Zn-SOD and Mn-SOD. Furthermore, our findings demonstrate that the lipid peroxidation against mitochondrial membrane may contribute to apoptosis of striatal neurons after transient focal ischemia. Thus our findings demonstrate that the protection of lipid peroxidation against mitochondrial membrane may offer a novel therapeutic strategy for brain stroke in humans.
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PMID:Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats. 1923 18

The oxidation of xanthine by xanthine oxidase (XO) or xanthine dehydrogenase represents an important source of reactive oxygen species (ROS), which contribute to the damaging consequences of cerebral ischemia, inflammation, and neurodegenerative disorders. However, both enzymes are also able to act on reduced nicotinamide adenine dinucleotide (NADH). The FAD binding site to which NADH binds is distinct from that of the xanthine binding site. We report that the combination of xanthine oxidase and NADH is toxic to cultures of cerebellar granule neurons. Protection by superoxide dismutase (Cu,Zn-SOD or Mn-SOD) or catalase indicates mediation of the toxicity by superoxide and hydrogen peroxide. In addition, pre-incubating XO with EDTA at concentrations as low as 2 microM, prevented the toxicity, indicating that a metal contaminating XO is involved in producing the toxic effects of XO/NADH. It is possible that such a metal might play a role in the toxicity of XO in vivo.
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PMID:Xanthine oxidase-induced neuronal death via the oxidation of NADH: prevention by micromolar EDTA. 1945 May 65

Cerebral ischemia and reperfusion increase superoxide anions (O(2)(*-)) in brain mitochondria. Manganese superoxide dismutase (Mn-SOD; SOD2), a primary mitochondrial antioxidant enzyme, scavenges superoxide radicals and its overexpression provides neuroprotection. However, the regulatory mechanism of Mn-SOD expression during cerebral ischemia and reperfusion is still unclear. In this study, we identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse Mn-SOD gene, and elucidated the mechanism of O(2)(*-) overproduction after transient focal cerebral ischemia (tFCI). We found that Mn-SOD expression is significantly reduced by reperfusion in the cerebral ischemic brain. We also found that activated STAT3 is usually recruited into the mouse Mn-SOD promoter and upregulates transcription of the mouse Mn-SOD gene in the normal brain. However, at early postreperfusion periods after tFCI, STAT3 was rapidly downregulated, and its recruitment into the Mn-SOD promoter was completely blocked. In addition, transcriptional activity of the mouse Mn-SOD gene was significantly reduced by STAT3 inhibition in primary cortical neurons. Moreover, we found that STAT3 deactivated by reperfusion induces accumulation of O(2)(*-) in mitochondria. The loss of STAT3 activity induced neuronal cell death by reducing Mn-SOD expression. Using SOD2-/+ heterozygous knock-out mice, we found that Mn-SOD is a direct target of STAT3 in reperfusion-induced neuronal cell death. Our study demonstrates that STAT3 is a novel transcription factor of the mouse Mn-SOD gene and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the mouse brain.
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PMID:Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia. 1947 27


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