Apoptotic cell death induced by beta-amyloid 1-42 peptide is cell type dependent.
beta-Amyloid peptide (A beta), a proteolytic fragment of the beta-amyloid precursor protein, is a major component of senile plaques in the brain of Alzheimer's disease patients. This neuropathological feature is accompanied by increased neuronal cell loss in the brain and there is evidence that A beta is directly neurotoxic. In the present study reduced cell viability in four different neuroblastoma cell types was observed after treatment with human A beta 1-42 for 1 day. Of the cell types tested rat PC12 and human IMR32 cells were most susceptible to A beta toxicity. Chromosomal condensation and fragmentation of nuclei were seen in PC12, NB2a, and B104 cells but not in IMR32 cells irrespective of their high sensitivity to A beta. Electrophoretic analysis of cellular DNA confirmed internucleosomal DNA fragmentation typical for apoptosis in all cell types except IMR32. These findings suggest that the form of A beta-induced cell death (necrosis or apoptosis) may depend on the cell type.
Gschwind
M
M
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Huber
G
G
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000473:pathology*; D009498:Neurotoxins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016564:Amyloid beta-Protein Precursor; D009498:Neurotoxins; D010446:Peptide Fragments; D000001:Calcimycin; D004247:DNA