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|Title:||Effect of amyloid beta-peptide on permeability transition pore: A comparative study||Authors:||Moreira, Paula I.
Santos, Maria S.
Rego, A. Cristina
|Issue Date:||2002||Citation:||Journal of Neuroscience Research. 69:2 (2002) 257-267||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 Abeta peptides. For this purpose, the following parameters were examined: mitochondrial membrane potential (DeltaPsim), respiration, swelling, ultrastructural morphology, and content of cytochrome c. Both peptides, Abeta25-35 (50 muM) and Abeta1-40 (2 muM), had a similar toxicity, exacerbating the effects of Ca2+, although, per se, they did not induce (PTP). In liver mitochondria, Abeta led to a drop in DeltaPsim and potentiated matrix swelling and disruption induced by Ca2+. In contrast, brain mitochondria, exposed to the same conditions, demonstrated a higher capacity to accumulate Ca2+ before the DeltaPsim drop and a slight increase of mitochondrial swelling compared with liver mitochondria. Furthermore, mitochondrial respiratory state 3 was depressed in the presence of Abeta, whereas state 4 was unaltered, resulting in an uncoupling of respiration. In both types of mitochondria, Abeta did not affect the content of cytochrome c. The DeltaPsim drop was reversed when Ca2+ 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 Abeta and/or Ca2+. It can be concluded that brain and liver mitochondria show a different susceptibility to the deleterious effect of Abeta peptide, brain mitochondria being more resistant to the potentiation by Abeta of Ca2+-induced PTP. © 2002 Wiley-Liss, Inc.||URI:||http://hdl.handle.net/10316/8324||DOI:||10.1002/jnr.10282||Rights:||openAccess|
|Appears in Collections:||FCTUC Ciências da Vida - Artigos em Revistas Internacionais|
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