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 A² amyloid peptide required for cytotoxicity i.e., A²(31-35) and A²(2535) peptides, was studied. We have shown that A²(31-35) peptide induces neurotoxicity in undifferentiated PC 12 cell via an apoptotic cell death pathway, including caspase activation and DNA fragmentation. A²(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 A²(25-35) peptide-induced neurotoxicity is not associated with any biochemical features of apoptosis. The differences observed between the neurotoxic properties of A²(31-35) and A²(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 A²(31-35) and A²(25-35) peptides affect in a different way the toxic behaviour of these two short amyloid fragments. Taken together our results suggest that A²(31-35) peptide induces cell death by apoptosis, unlike the A²(25-35) peptide and that role played by methionine-35 in A² induced neurotoxicity might be related to the A² aggregation state.