Amyloid beta-peptide promotes permeability transition pore in brain mitochondria.
In this work the effect of the neurotoxic amino acid sequence, Abeta25-35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (deltapsim), mitochondrial respiration and the calcium fluxes were examined. It was observed that Abeta25-35, in the presence of Ca2+, decreased the deltapsim, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Abeta25-35 (Abeta35-25) did not promote the PTP. The alterations promoted by Abeta35-25 and/or Ca2+ could be reversed when Ca2 was removed by EGTA or when ADP plus oligomycin were present. The pretreatment with CsA or ADP plus oligomycin prevented the deltapsim drop and preserved the capacity of mitochondria to accumulate Ca2+. These results suggest that Abeta25-35 can promote the PTP induced by Ca2+.
Moreira
P I
PI
Center for Neuroscience and Cellular Biology of Coimbra, Department of Zoology, Portugal.
Santos
M S
MS
Moreno
A
A
Oliveira
C
C
D000244:Adenosine Diphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D019069:Cell Respiration / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014475:Uncoupling Agents / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D009840:Oligomycins; D014475:Uncoupling Agents; C439320:amyloid beta-protein (25-36); D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D002118:Calcium