Abeta(31-35) peptide induce apoptosis in PC 12 cells: contrast with Abeta(25-35) peptide and examination of underlying mechanisms.
The toxic behaviour of the two shorter sequences of the native Abeta amyloid peptide required for cytotoxicity i.e., Abeta(31-35) and Abeta(25-35) peptides, was studied. We have shown that Abeta(31-35) peptide induces neurotoxicity in undifferentiated PC 12 cell via an apoptotic cell death pathway, including caspase activation and DNA fragmentation. Abeta(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 Abeta(25-35) peptide-induced neurotoxicity is not associated with any biochemical features of apoptosis. The differences observed between the neurotoxic properties of Abeta(31-35) and Abeta(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 Abeta(31-35) and Abeta(25-35) peptides affect in a different way the toxic behaviour of these two short amyloid fragments. Taken together our results suggest that Abeta(31-35) peptide induces cell death by apoptosis, unlike the Abeta(25-35) peptide and that role played by methionine-35 in Abeta induced neurotoxicity might be related to the Abeta aggregation state.
Misiti
Francesco
F
Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, Largo F. Vito 1-00168 Rome, Italy. fmisiti@rm.unicatt.it
Sampaolese
Beatrice
B
Pezzotti
Michela
M
Marini
Stefano
S
Coletta
Massimo
M
Ceccarelli
Lia
L
Giardina
Bruno
B
Clementi
Maria Elisabetta
ME
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D008715:Methionine / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C113042:amyloid beta-protein (31-35); D008715:Methionine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases