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자연과학대학
생명과학전공
Journal papers
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Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins
Title
Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins
Authors
Lee J.E.
;
Kang J.S.
;
Shin I.C.
;
Lee S.-J.
;
Hyun D.-H.
;
Lee K.S.
;
Koh H.C.
Ewha Authors
현동훈
SCOPUS Author ID
현동훈
Issue Date
2011
Journal Title
NeuroToxicology
ISSN
0161-813X
Citation
NeuroToxicology vol. 32, no. 6, pp. 702 - 710
Indexed
SCI; SCIE; SCOPUS
Document Type
Article
Abstract
A number of epidemiological studies have demonstrated a strong association between the incidence of neurodegenerative disease and pesticide exposure. Fluazinam (FZN) is a preventative fungicide from the pyridinamine group that was introduced in the 1990s and that quickly established itself as a new standard for the control of blight caused by Phytophthora infestans in potatoes. We used human neuroblastoma SH-SY5Y cells to investigate mechanisms of neuronal cell death in response to FZN and showed that FZN was cytotoxic to SH-SY5Y cells in a concentration- and time-dependent manner. Additionally, we showed that FZN treatment significantly decreased the neuron numbers including dopaminergic neurons and mitochondrial complex I activity. The cytotoxic effects of FZN were associated with an increase in reactive oxygen species (ROS) generation because pretreatment with N-acetyl cysteine, an anti-oxidant, reduced cell death. We showed that neuronal cell death in response to FZN was due to apoptosis because FZN increased cytochrome C release into the cytosol and activated caspase-3 through the accumulation of p53. FZN also reduced the levels of Bcl-2 protein but increased the levels of Bax. Our results provide insight into the molecular mechanisms of FZN-induced apoptosis in neuronal cells. © 2011.
DOI
10.1016/j.neuro.2011.08.004
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