期刊
NEUROTOXICOLOGY
卷 32, 期 6, 页码 935-943出版社
ELSEVIER
DOI: 10.1016/j.neuro.2011.04.006
关键词
Fipronil; SH-SY5Y; Apoptosis; Mitochondrial uncoupler; Anaerobic glycolysis
资金
- ISCIII (Ministerio de Ciencia e Innovacion, Spain) [PI070400, CP0800010]
- Ministerio de Ciencia e Innovacion, Spain [SAF2010-14993, BIO2008-04542-C02-02]
- Junta de Extremadura, Spain [GR10054]
- FUNDESALUD [PRIS10013]
- Junta de Extremadura
- Universidad de Extremadura
- Ministerio de Educacion
- Miguel Servet contract
Fipronil is a phenylpyrazole insecticide known to elicit neurotoxicity via an interaction with ionotropic receptors, namely GABA and glutamate receptors. Recently, we showed that fipronil and other phenylpyrazole compounds trigger cell death in Caco-2 cells. In this study, we investigated the mode of action and the type of cell death induced by fipronil in SH-SY5Y human neuroblastoma cells. Flow cytometric and western blot analyses demonstrated that fipronil induces cellular events belonging to the apoptosis process, such as mitochondrial potential collapse, cytochrome c release, caspase-3 activation, nuclear condensation and phosphatidylserine externalization. In addition, fipronil induces a rapid ATP depletion with concomitant activation of anaerobic glycolysis. This cellular response is characteristic of mitochondrial injury associated with a defect of the respiration process. Therefore, we also investigated the effect of fipronil on the oxygen consumption in isolated mitochondria. Interestingly, we show for the first time that fipronil is a strong uncoupler of oxidative phosphorylation at relative low concentrations. Thus in this study, we report a new mode of action by which the insecticide fipronil could triggers apoptosis. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据