title: Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells.
abstract: Fipronil is the first phenylpyrazole insecticide widely used in controlling pests, including pyrethroid, organophosphate and carbamate insecticides. It is generally accepted that fipronil elicits neurotoxicity via interactions with GABA and glutamate receptors, although alternative mechanisms have recently been proposed. This study evaluates the genotoxicity of fipronil and its likely mode of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated the concentration- and time-dependent S2 cell proliferation. Intracellular biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major executioner caspase downstream of caspase-9 in Drosophila, enzyme activity assays were used to determine the activities of caspase-3 and caspase-9. Our results indicated that fipronil effectively induced apoptosis in Drosophila S2 cells through caspase-dependent mitochondrial pathways.
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Baoyan
authors: B
authors: Zhang
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: zhipingxu@ecust.edu.cn.
authors: Zhiping
authors: Z
authors: Xu
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China.
authors: Yixi
authors: Y
authors: Zhang
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Xusheng
authors: X
authors: Shao
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Xiaoyong
authors: X
authors: Xu
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Jiaogao
authors: J
authors: Cheng
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Zhong
authors: Z
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007306:Insecticides / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D011720:Pyrazoles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D029721:Drosophila Proteins; D007306:Insecticides; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9; C082360:fipronil
keywords: Apoptosis; Caspase; Cytochrome c; Drosophila S2 cells; Fipronil; Mitochondrion