The Arctic Alzheimer mutation enhances sensitivity to toxic stress in human neuroblastoma cells.
The E693G (Arctic) mutation of the amyloid precursor protein was recently found to lead to early-onset Alzheimer's disease in a Swedish family. In the present study, we report that the Arctic mutation decreases cell viability in human neuroblastoma cells. The cell viability, as measured by the MTT assay and propidium iodide staining, was further compromised following exposure to calcium ionophore A23187, microtubule-binding colchicine or oxidative stress inducer hydrogen peroxide. The manner of cell death was found to be apoptotic. During apoptosis, cells with the Arctic mutation also decreased their secretion of beta-secretase cleaved amyloid precursor protein. The enhanced sensitivity to toxic stress in cells with the Arctic mutation most likely contributes to the pathogenic pathway leading to Alzheimer's disease.
Sennvik
Kristina
K
Section of Experimental Geriatrics, Neurotec, Karolinska Institutet, KFC Novum, plan 4, 141 86 Huddinge, Sweden. kristina.sennvik@neurotec.ki.se
Nilsberth
Camilla
C
Stenh
Charlotte
C
Lannfelt
Lars
L
Benedikz
Eirikur
E
D000470:Alkaloids / Q000009:adverse effects; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D000001:Calcimycin / Q000009:adverse effects; D003078:Colchicine / Q000009:adverse effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D007476:Ionophores / Q000009:adverse effects; D009154:Mutation; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007476:Ionophores; D000001:Calcimycin; D006861:Hydrogen Peroxide; D003078:Colchicine