In order to clarify the basis of neuronal toxicity exerted by the shortest active peptides of amyloid beta-protein (Abeta), the toxic effects of Abeta(31-35) and Abeta(25-35) peptides on isolated rat brain mitochondria were investigated. The results show that exposure of isolated rat brain mitochondria to Abeta(31-35) and Abeta(25-35) peptides determines: (i) release of cytochrome c; (ii) mitochondrial swelling and (iii) a significant reduction in mitochondrial oxygen consumption. In contrast, the amplitude of these events resulted attenuated in isolated brain mitochondria exposed to the Abeta(31-35)Met35(OX) in which methionine-35 was oxidized to methionine sulfoxide. The Abeta peptide derivative with norleucine substituting Met-35, i.e., Abeta(31-35)Nle-35, had not effect on any of the biochemical parameters tested. We have further characterized the action of Abeta(31-35) and Abeta(25-35) peptides on neuronal cells. Taken together our result indicate that Abeta(31-35) and Abeta(25-35) peptides in non-aggregated form, i.e., predominantly monomeric, are strongly neurotoxic, having the ability to enter within the cells, determining mitochondrial damage with an evident trigger of apoptotic signals. Such a mechanism of toxicity seems to be dependent by the redox state of methionine-35.

Clementi, M., Marini, S., Coletta, M., Orsini, F., Giardina, B., Misiti, F. (2005). Abeta(31-35) and Abeta(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35. FEBS LETTERS, 579(13), 2913-2918 [10.1016/j.febslet.2005.04.041].

Abeta(31-35) and Abeta(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35

MARINI, STEFANO;COLETTA, MASSIMILIANO;
2005

Abstract

In order to clarify the basis of neuronal toxicity exerted by the shortest active peptides of amyloid beta-protein (Abeta), the toxic effects of Abeta(31-35) and Abeta(25-35) peptides on isolated rat brain mitochondria were investigated. The results show that exposure of isolated rat brain mitochondria to Abeta(31-35) and Abeta(25-35) peptides determines: (i) release of cytochrome c; (ii) mitochondrial swelling and (iii) a significant reduction in mitochondrial oxygen consumption. In contrast, the amplitude of these events resulted attenuated in isolated brain mitochondria exposed to the Abeta(31-35)Met35(OX) in which methionine-35 was oxidized to methionine sulfoxide. The Abeta peptide derivative with norleucine substituting Met-35, i.e., Abeta(31-35)Nle-35, had not effect on any of the biochemical parameters tested. We have further characterized the action of Abeta(31-35) and Abeta(25-35) peptides on neuronal cells. Taken together our result indicate that Abeta(31-35) and Abeta(25-35) peptides in non-aggregated form, i.e., predominantly monomeric, are strongly neurotoxic, having the ability to enter within the cells, determining mitochondrial damage with an evident trigger of apoptotic signals. Such a mechanism of toxicity seems to be dependent by the redox state of methionine-35.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Con Impact Factor ISI
Rats; Animals; Rats, Sprague-Dawley; Peptide Fragments; Apoptosis; Amyloid beta-Peptides; Methionine; Male; PC12 Cells
Clementi, M., Marini, S., Coletta, M., Orsini, F., Giardina, B., Misiti, F. (2005). Abeta(31-35) and Abeta(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35. FEBS LETTERS, 579(13), 2913-2918 [10.1016/j.febslet.2005.04.041].
Clementi, M; Marini, S; Coletta, M; Orsini, F; Giardina, B; Misiti, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/29348
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