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Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins.
Neurotoxicology. 2011 Dec; 32(6):702-10.N

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 1990 s 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.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Hanyang University, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21907236

Citation

Lee, Jeong Eun, et al. "Fluazinam-induced Apoptosis of SH-SY5Y Cells Is Mediated By P53 and Bcl-2 Family Proteins." Neurotoxicology, vol. 32, no. 6, 2011, pp. 702-10.
Lee JE, Kang JS, Shin IC, et al. Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins. Neurotoxicology. 2011;32(6):702-10.
Lee, J. E., Kang, J. S., Shin, I. C., Lee, S. J., Hyun, D. H., Lee, K. S., & Koh, H. C. (2011). Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins. Neurotoxicology, 32(6), 702-10. https://doi.org/10.1016/j.neuro.2011.08.004
Lee JE, et al. Fluazinam-induced Apoptosis of SH-SY5Y Cells Is Mediated By P53 and Bcl-2 Family Proteins. Neurotoxicology. 2011;32(6):702-10. PubMed PMID: 21907236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluazinam-induced apoptosis of SH-SY5Y cells is mediated by p53 and Bcl-2 family proteins. AU - Lee,Jeong Eun, AU - Kang,Jin Sun, AU - Shin,In Chul, AU - Lee,Soo-Jin, AU - Hyun,Dong-Hoon, AU - Lee,Kyung Suk, AU - Koh,Hyun Chul, Y1 - 2011/09/03/ PY - 2011/03/30/received PY - 2011/07/26/revised PY - 2011/08/21/accepted PY - 2011/9/13/entrez PY - 2011/9/13/pubmed PY - 2012/5/4/medline SP - 702 EP - 10 JF - Neurotoxicology JO - Neurotoxicology VL - 32 IS - 6 N2 - 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 1990 s 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. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/21907236/Fluazinam_induced_apoptosis_of_SH_SY5Y_cells_is_mediated_by_p53_and_Bcl_2_family_proteins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(11)00133-1 DB - PRIME DP - Unbound Medicine ER -