Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic encephalopathy, characterized by cognitive deficits involves hyperglycemia-induced oxidative stress. Impaired mitochondrial functions might play an important role in accelerated oxidative damage observed in diabetic brain. The aim of the present study was to examine the role of mitochondrial oxidative stress and dysfunctions in the development of diabetic encephalopathy along with the neuroprotective potential of N-acetylcysteine (NAC). Chronic hyperglycemia accentuated mitochondrial oxidative stress in terms of increased ROS production and lipid peroxidation. Significant decrease in Mn-SOD activity along with protein and non-protein thiols was observed in the mitochondria from diabetic brain. The activities of mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase were decreased in the diabetic brain. Increased mitochondrial oxidative stress and dysfunctions were associated with increased cytochrome c and active caspase-3 levels in cytosol. Electron microscopy revealed mitochondrial swelling and chromatin condensation in neurons of diabetic animals. NAC administration, on the other hand was found to significantly improve diabetes-induced biochemical and morphological changes, bringing them closer to the controls. The results from the study provide evidence for the role of mitochondrial oxidative stress and dysfunctions in the development of diabetic encephalopathy and point towards the clinical potential of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and/or delaying the progression of CNS complications.
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PMID:Protective effect of N-acetylcysteine supplementation on mitochondrial oxidative stress and mitochondrial enzymes in cerebral cortex of streptozotocin-treated diabetic rats. 2105 8

Diabetic encephalopathy, a proven complication of diabetes is associated with gradually developing end-organ damage in the CNS increasing the risk of stroke, cognitive dysfunction or Alzheimer's disease. This study investigated the response of rat cortical mitochondria to streptozotocin-induced diabetes and the potential for fish oil emulsion (FOE) to modulate mitochondrial function. Diabetes-induced deregulation of the respiratory chain function as a result of diminished complex I activity (CI) and cytochrome c oxidase hyperactivity was associated with attenuation of antioxidant defense of isolated cortical mitochondria, monitored by SOD activity, the thiol content, the dityrosine and protein-lipid peroxidation adduct formation. A parallel reduction in phosphorylation of the energy marker AMPK has pointed out to disrupted energy homeostasis. Dietary FOE administration partially preserved CI activity, restored AMPK phosphorylation, but was unable to attenuate oxidative stress and prevent the shift toward saturated fatty acids in the cardiolipin composition. Moreover, diabetes has induced alterations in the protein expression of the regulatory COX4 subunit of cytochrome c oxidase, in the inhibitory factor IF1 and ATP5A subunit of F0F1-ATP synthase, in the uncoupling protein UCP4 and supramolecular organization of the respiratory complexes. FOE administration to diabetic rats has partially reversed these alterations. This study suggests diabetes-induced dysfunction of brain cortical mitochondria and its modulation by FOE administration. The intricate diabetic milieu and the n-3 FA nutrigenomic strength, however require further investigations to be able to unequivocally evaluate neuroprotective and adverse effects of FOE supplementation on the diabetic brain function.
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PMID:Diabetes-induced abnormalities of mitochondrial function in rat brain cortex: the effect of n-3 fatty acid diet. 2852 35