Beta-amyloid-induced activation of caspase-3 in primary cultures of rat neurons.
It is known that beta-amyloid peptide (Abeta) contributes to the neurodegeneration in Alzheimer's disease (AD) and operates through activation of an apoptotic pathway. Apoptotic signal is driven by a family of cysteine proteases called caspases. The beta-amyloid precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated beta-amyloid peptide formation. Cerebellar neurons from rat pups were treated with the aged Abeta(25-35) at 1 and 5 microM and fluorescence assays of caspase activity performed over 4 days. We observed an increase in caspase activity after 48 h treatment in both 1 and 5 microM treated cells, then (72-96 h) caspase activity decreased to control values. The data presented support the hypothesis that Abeta(25-35)-induced apoptosis is mediated by the activation of Caspase-3 and that this is a transient effect.
Marín
N
N
Neurophysiology and Neurotoxicology Unit, Department of Physiology, School of Medicine and Dentistry, University of Valencia, Av. Blasco Ibañez 17, E-46010, Valencia, Spain.
Romero
B
B
Bosch-Morell
F
F
Llansola
M
M
Felipo
V
V
Romá
J
J
Romero
F J
FJ
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases