CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats.
Using brain mitochondria isolated from 20-month-old diabetic Goto-Kakizaki rats, we evaluated the efficacy of CoQ10 treatment against mitochondrial dysfunction induced by Abeta1-40. For that purpose, several mitochondrial parameters were evaluated: respiratory indexes (RCR and ADP/O ratio), transmembrane potential (DeltaPsim), repolarization lag phase, repolarization and ATP levels and the capacity of mitochondria to produce hydrogen peroxide. We observed that 4 microM Abeta1-40 induced a significant decrease in the RCR and ATP content and a significant increase in hydrogen peroxide production. CoQ10 treatment attenuated the decrease in oxidative phosphorylation efficiency and avoided the increase in hydrogen peroxide production induced by the neurotoxic peptide. These results indicate that CoQ10 treatment counteracts brain mitochondrial alterations induced by Abeta1-40 suggesting that CoQ10 therapy can help to avoid a drastic energy deficiency that characterizes diabetes and Alzheimer's disease pathophysiology.
Moreira
Paula I
PI
Center for Neuroscience and Cell Biology, Department of Zoology-Faculty of Sciences and Technology, University of Coimbra, 3004-517 Coimbra, Portugal.
Santos
Maria S
MS
Sena
Cristina
C
Nunes
Elsa
E
Seiça
Raquel
R
Oliveira
Catarina R
CR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects; D003067:Coenzymes; D003924:Diabetes Mellitus, Type 2; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D003067:Coenzymes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D014451:Ubiquinone; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; C024989:coenzyme Q10