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  2. 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

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 Lett. 2005 May 23;579(13):2913-8. doi: 10.1016/j.febslet.2005.04.041.
M Elisabetta Clementi 1 Stefano Marini Massimo Coletta Federica Orsini Bruno Giardina Francesco Misiti
Affiliations

Affiliation

  • 1 Institute of Biochemistry and Clinical Biochemistry and CNR Institute Chimica del Riconoscimento Molecolare Faculty of Medicine, Catholic University Largo F. Vito 1, Rome, Italy. elisabetta.clement@icrm.cr.it
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.

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