A beta(31-35) peptide induce apoptosis in PC 12 cells: Contrast with A beta(25-35) peptide and examination of underlying mechanisms

The toxic behaviour of the two shorter sequences of the native Aβ amyloid peptide required for cytotoxicity i.e., Aβ(31-35) and Aβ(2535) peptides, was studied. We have shown that Aβ(31-35) peptide induces neurotoxicity in undifferentiated PC 12 cell via an apoptotic cell death pathway, including caspase activation and DNA fragmentation. Aβ(25-35) peptide, like the shorter amyloid peptide has the ability to induce neurotoxicity, as evaluated by the MTS reduction assay and by adherent cell count, but the Aβ(25-35) peptide-induced neurotoxicity is not associated with any biochemical features of apoptosis. The differences observed between the neurotoxic properties of Aβ(31-35) and Aβ(25-35) peptides might result on their different ability to be internalised within the neuronal cells. Furthermore, this study reveals that the redox state of methionine residue, C-terminal in Aβ(31-35) and Aβ(25-35) peptides affect in a different way the toxic behaviour of these two short amyloid fragments. Taken together our results suggest that Aβ(31-35) peptide induces cell death by apoptosis, unlike the Aβ(25-35) peptide and that role played by methionine-35 in Aβ induced neurotoxicity might be related to the Aβ aggregation state. © 2005 Elsevier Ltd. All rights reserved.