PMID- 22421270
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20131121
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 211
IP  - 1
DP  - 2012 May 20
TI  - Reactive oxygen species and mitogen-activated protein kinase induce apoptotic 
      death of SH-SY5Y cells in response to fipronil.
PG  - 18-28
LID - 10.1016/j.toxlet.2012.02.022 [doi]
AB  - There are multiple lines of evidence showing that environmental toxicants 
      including pesticides may contribute to neuronal cell death. Fipronil (FPN) is a 
      phenylpyrazole insecticide that acts on insect GABA receptors. Although the 
      action of FPN is restricted to insect neuronal or muscular transmitter systems, a 
      few studies have assessed the effects of this neurotoxicant on neuronal cell 
      death distinct from an insect. To determine the mechanisms underlying FPN-induced 
      neuronal cell death, we evaluated the ability of this chemical to induce 
      oxidative stress and studied the involvement of mitogen activated protein kinases 
      (MAPKs) in FPN-induced apoptosis stress in human neuroblastoma SH-SY5Y (SH-SY5Y) 
      cells. Exposure of SH-SY5Y cells to FPN led to the production of reactive oxygen 
      species (ROS) and apoptotic cell death via activation of caspase-9 and caspase-3. 
      Interestingly, the antioxidant, N-acetyl-cysteine (NAC) attenuated apoptotic cell 
      death and ROS production induced by FPN. These results indicated that oxidative 
      stress plays a central role in FPN-induced cytotoxicity. Mitochondrial complex I 
      activity was also inhibited by FPN treatment. These finding indicate that FPN 
      triggers intrinsic apoptosis via the mitochondrial signaling pathway that is 
      initiated by the generation of ROS. Furthermore, FPN treatment induced 
      phosphorylation of MAPK members. Activation of these protein kinases by FPN was 
      involved in the onset of apoptosis as inhibitors specific to these kinases 
      protect against FPN-induced cell death as well as ROS generation. Our data 
      indicate that FPN-induced apoptosis is mediated primarily by the generation of 
      ROS and activation of MAPK members followed by activation of the intrinsic 
      apoptotic pathway.
CI  - Crown Copyright (c) 2012. Published by Elsevier Ireland Ltd. All rights reserved.
FAU - Ki, Yeo-Woon
AU  - Ki YW
AD  - Department of Pharmacology, College of Medicine, Hanyang University, Sungdong-Gu, 
      Heandang-Dong 17, 133-791 Seoul, Republic of Korea.
FAU - Lee, Jeong Eun
AU  - Lee JE
FAU - Park, Jae Hyeon
AU  - Park JH
FAU - Shin, In Chul
AU  - Shin IC
FAU - Koh, Hyun Chul
AU  - Koh HC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120307
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Antioxidants)
RN  - 0 (Insecticides)
RN  - 0 (Pyrazoles)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - QGH063955F (fipronil)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Antioxidants/pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Insecticides/*pharmacology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neuroblastoma/metabolism
MH  - Oxidative Stress/drug effects
MH  - Pyrazoles/*pharmacology
MH  - Reactive Oxygen Species/*metabolism
EDAT- 2012/03/17 06:00
MHDA- 2012/06/30 06:00
CRDT- 2012/03/17 06:00
PHST- 2011/12/21 00:00 [received]
PHST- 2012/02/24 00:00 [revised]
PHST- 2012/02/27 00:00 [accepted]
PHST- 2012/03/17 06:00 [entrez]
PHST- 2012/03/17 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
AID - S0378-4274(12)00078-1 [pii]
AID - 10.1016/j.toxlet.2012.02.022 [doi]
PST - ppublish
SO  - Toxicol Lett. 2012 May 20;211(1):18-28. doi: 10.1016/j.toxlet.2012.02.022. Epub 
      2012 Mar 7.