Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells.
The cytoprotective effect of vinpocetine [14-ethoxycarbonyl-(3alpha, 16alpha-ethyl)-14,15-eburnamine] was investigated on PC12 cells treated with the amyloid beta-peptides (Abeta) for 24 hours. Vinpocetine was shown to protect cells from the inhibition in redox status induced by exposure to Abeta25-35 and Abeta1-40, the maximal protection being achieved at a vinpocetine concentration of 40 microM. At this concentration, vinpocetine blocked the inhibition of the mitochondrial respiratory chain complexes II-III and IV and completely abolished the depletion of pyruvate levels induced by toxic concentrations of Abeta peptides. Furthermore, the accumulation of ROS in cells exposed to Abeta25-35 and Abeta1-40 evaluated using the fluorescent probe 2',7'-dichlorofluorescin (DCF), was reduced in the presence of 40 microM vinpocetine. Taken together, the data presented herein demonstrate that vinpocetine protects cells from Abeta toxicity, preventing the generation of oxidative stress due to the excessive accumulation of ROS. This study suggests that vinpocetine can exert neuroprotective properties which might be of importance and contribute to its clinical efficacy in the treatment of Alzheimer's disease or other neurodegenerative disorders in which oxidative stress is involved.
Pereira
C
C
Center for Neuroscience of Coimbra, Faculty of Medicine, University of Coimbra, Portugal. cpereira@cnc.uc.pt
Agostinho
P
P
Oliveira
C R
CR
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D004579:Electron Transport; D006019:Glycolysis; D008928:Mitochondria / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014748:Vinca Alkaloids / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D018697:Nootropic Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014748:Vinca Alkaloids; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C013983:vinpocetine; D019289:Pyruvic Acid