Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins

Jeong Eun Lee, Jin Sun Kang, In Chul Shin, Soo Jin Lee, Dong Hoon Hyun, Kyung Suk Lee, Hyun Chul Koh

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish
Pages (from-to)702-710
Number of pages9
JournalNeuroToxicology
Volume32
Issue number6
DOIs
StatePublished - Dec 2011

Bibliographical note

Funding Information:
This work was supported by a grant from the “ Research Program for Agriculture Science & Technology Development ( PJ006483200901 )” Rural Development Administration, Republic of Korea and by a grant from the Korea Science and Engineering Foundation ( 2010-0029506 ) through the MRC for Regulation of Stem Cell Behaviors at Hanyang University College of Medicine, Republic of Korea.

Keywords

  • Apoptosis
  • Bcl-2 family
  • Fluazinam
  • P53
  • Reactive oxygen species

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