A comparative study of beta-amyloid peptides Abeta1-42 and Abeta25-35 toxicity in organotypic hippocampal slice cultures.
Accumulation of the neurotoxic amyloid beta-peptide (Abeta) in the brain is a hallmark of Alzheimer's disease (AD). Several synthetic Abeta peptides have been used to study the mechanisms of toxicity. Here, we sought to establish comparability between two commonly used Abeta peptides Abeta1-42 and Abeta25-35 on an in vitro model of Abeta toxicity. For this purpose we used organotypic slice cultures of rat hippocampus and observed that both Abeta peptides caused similar toxic effects regarding to propidium iodide uptake and caspase-3 activation. In addition, we also did not observe any effect of both peptides on Akt and PTEN phosphorylation; otherwise the phosphorylation of GSK-3beta was increased. Although further studies are necessary for understanding mechanisms underlying Abeta peptide toxicity, our results provide strong evidence that Abeta1-42 and the Abeta25-35 peptides induce neural injury in a similar pattern and that Abeta25-35 is a convenient tool for the investigation of neurotoxic mechanisms involved in AD.
Frozza
Rudimar Luiz
RL
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Av. Ramiro Barcelos, 2600 - anexo, Porto Alegre, RS, CEP 90035-003, Brazil.
Horn
Ana Paula
AP
Hoppe
Juliana Bender
JB
Simão
Fabrício
F
Gerhardt
Daniéli
D
Comiran
Ricardo Argenta
RA
Salbego
Christianne Gazzana
CG
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; D053148:Caspase 3