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)

In this study, we have investigated the effects of manganese superoxide dismutase (SOD2 or MnSOD) deficiency on mitochondrial function and oxidative stress during Chagas disease. For this, C57BL/6 wild type (WT) and MnSOD+/- mice were infected with Trypanosoma cruzi (Tc), and evaluated at 150 days' post-infection that corresponded to chronic disease phase. Genetic deletion of SOD2 decreased the expression and activity of MnSOD, but it had no effect on the expression of other members of the SOD family. The myocardial expression and activity of MnSOD were significantly decreased in chronically infected WT mice, and it was further worsened in MnSOD+/- mice. Chronic T. cruzi infection led to a decline in mitochondrial complex I and complex II driven, ADP-coupled respiration and ATP synthesis in the myocardium of WT mice. The baseline oxidative phosphorylation (OXPHOS) capacity in MnSOD+/- mice was decreased, and it had an additive effect on mitochondrial dysregulation of ATP synthesis capacity in chagasic myocardium. Further, MnSOD deficiency exacerbated the mitochondrial rate of reactive oxygen species (ROS) production and myocardial oxidative stress (H2O2, protein carbonyls, malondialdehyde, and 4-hydroxynonenal) in Chagas disease. Peripheral and myocardial parasite burden and inflammatory response (myeloperoxidase, IL-6, lactate dehydrogenase, inflammatory infiltrate) were increased in all chagasic WT and MnSOD+/- mice. We conclude that MnSOD deficiency exacerbates the loss in mitochondrial function and OXPHOS capacity and enhances the myocardial oxidative damage in chagasic cardiomyopathy. Mitochondria targeted, small molecule mitigators of MnSOD deficiency will offer potential benefits in averting the mitochondrial dysfunction and chronic oxidative stress in Chagas disease.
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PMID:Manganese superoxide dismutase deficiency exacerbates the mitochondrial ROS production and oxidative damage in Chagas disease. 3004 89

Cognitive issues in stroke arise as a result of reperfusion of a clogged artery, which is reported to exacerbate the injury in the brain leading to oxidative stress. Through the present work, we try to understand the regional variations across brain regions mainly cortex and striatum associated with the progression of ischemia-reperfusion injury (IRI). In a rat model of IRI, the influence of varying ischemia and reperfusion times on the biochemical phases across the brain regions were monitored. IRI resulted in the blood-brain barrier disruption and developed mild areas of risk. The brain's tolerance towards IRI indicated a progressive trend in the injury and apoptosis from ischemia to reperfusion that was supported by the activities of plasma lactate dehydrogenase and tissue caspase-3. Cognitive impairment in these rats was an implication of cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) that persisted by 24-h reperfusion. The oxidative stress was prominent in the cortex than the striatum and was supported by the lower ATP level. Upregulated Mn-SOD expression leading to a preserved mitochondria in the striatum could be attributed to the regional protection. Overall, a progression of IRI was observed from striatum to cortex leading to 5-day cognitive decline.
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PMID:Eventual analysis of global cerebral ischemia-reperfusion injury in rat brain: a paradigm of a shift in stress and its influence on cognitive functions. 3102 39


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