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β‐Amyloid Induces Oxidative DNA Damage and Cell Death through Activation of c‐Jun N Terminal Kinase
Author(s) -
JANG JUNGHEE,
SURH YOUNGJOON
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04639.x
Subject(s) - oxidative stress , programmed cell death , senile plaques , reactive oxygen species , dna damage , chemistry , apoptosis , microbiology and biotechnology , tunel assay , c jun , amyloid beta , presenilin , intracellular , alzheimer's disease , biology , biochemistry , dna , peptide , pathology , medicine , gene , disease , transcription factor
A bstract : Oxidative stress induced by reactive oxygen species has been implicated in the pathophysiology of many neurodegenerative disorders including Alzheimer's disease (AD). In this study, we have investigated the molecular mechanisms underlying oxidative cell death induced by β‐amyloid, a neurotoxic peptide associated with senile plaques found in the brains of patients with AD. PC12 cells treated with β‐amyloid underwent apoptotic cell death as determined by characteristic morphological features, cleavage of poly(ADP‐ribose)polymerase, and positive in situ terminal‐end labeling (TUNEL). Furthermore, β‐amyloid treatment led to activation of c‐Jun N terminal kinase (JNK) and intracellular accumulation of ROS. In another experiment, β‐amyloid caused strand scission in φX174 DNA in the presence of ferrous iron. These findings suggest that production of ROS and subsequent activation of JNK play an important role in β‐amyloid‐induced apoptotic cell death.