Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic
Ivanović-Burmazović, Ivana S
Filipović, Milos R
Korac, Aleksandra B
Markelić, Milica B
Velicković, Ksenija D
Buzadžić, Biljana J.
Korać, Bato M.
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Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl-2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level >= 12 mM. Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1 alpha - the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1 alpha to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated. To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl-2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder. (C) 2013 Elsevier Inc. All rights reserved.
Извор:Brain Research Bulletin, 2013, 99, null, 153-33