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Effect of amyloid β‐peptide on permeability transition pore: A comparative study
Author(s) -
Moreira Paula I.,
Santos Maria S.,
Moreno António,
Rego A. Cristina,
Oliveira Catarina
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10282
Subject(s) - oligomycin , mitochondrion , mitochondrial permeability transition pore , egta , biophysics , cytochrome c , biochemistry , respiration , biology , chemistry , calcium , anatomy , programmed cell death , apoptosis , atpase , organic chemistry , enzyme
Abstract A potentially central factor in neurodegeneration is the permeability transition pore (PTP). Because of the tissue‐specific differences in pore properties, we directly compared isolated brain and liver mitochondria responses to the neurotoxic Aβ peptides. For this purpose, the following parameters were examined: mitochondrial membrane potential (ΔΨm), respiration, swelling, ultrastructural morphology, and content of cytochrome c. Both peptides, Aβ 25–35 (50 μM) and Aβ 1–40 (2 μM), had a similar toxicity, exacerbating the effects of Ca 2+ , although, per se, they did not induce (PTP). In liver mitochondria, Aβ led to a drop in ΔΨm and potentiated matrix swelling and disruption induced by Ca 2+ . In contrast, brain mitochondria, exposed to the same conditions, demonstrated a higher capacity to accumulate Ca 2+ before the ΔΨm drop and a slight increase of mitochondrial swelling compared with liver mitochondria. Furthermore, mitochondrial respiratory state 3 was depressed in the presence of Aβ, whereas state 4 was unaltered, resulting in an uncoupling of respiration. In both types of mitochondria, Aβ did not affect the content of cytochrome c. The ΔΨm drop was reversed when Ca 2+ was removed by EGTA or when ADP plus oligomycin was present. Pretreatment with cyclosporin A or ADP plus oligomycin prevented the deleterious effects promoted by Aβ and/or Ca 2+ . It can be concluded that brain and liver mitochondria show a different susceptibility to the deleterious effect of Aβ peptide, brain mitochondria being more resistant to the potentiation by Aβ of Ca 2+ ‐induced PTP. © 2002 Wiley‐Liss, Inc.