title: Spinosad induces programmed cell death involves mitochondrial dysfunction and cytochrome C release in Spodoptera frugiperda Sf9 cells.
abstract: Spinosad, a reduced-risk insecticide, acts on the nicotinic acetylcholine receptors and the gamma-aminobutyric acid receptor in the nervous system of target insects. However, its mechanism of action in non-neural insect cells is unclear. This study aimed to evaluate mitochondrial functional changes associated with spinosad in Spodoptera frugiperda (Sf9) insect cells. Our results indicate that in Sf9 cells, spinosad induces programmed cell death and mitochondrial dysfunction through enhanced reactive oxygen species production, mitochondrial permeability transition pore (mPTP) opening, and mitochondrial membrane potential collapse, eventually leading to cytochrome C release and apoptosis. The cytochrome C release induced by spinosad treatment was partly inhibited by the mPTP inhibitors cyclosporin A and bongkrekic acid. Subsequently, we found that spinosad downregulated Bcl-2 expression and upregulated p53 and Bax expressions, activated caspase-9 and caspase-3, and triggered PARP cleavage in Sf9 cells. These findings suggested that spinosad-induced programmed cell death was modulated by mitochondrial dysfunction and cytochrome C release.
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: College of Life and Environmental Sciences, Shanghai Normal University, Shanghai, 200234, China.
authors.forename: Jufang
authors.initials: J
authors.lastname: Gao
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xu
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China. Electronic address: taolm@ecust.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism*; D004338:Drug Combinations; D007306:Insecticides / Q000633:toxicity*; D018942:Macrolides / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species / Q000378:metabolism; D061987:Sf9 Cells / Q000378:metabolism; D018411:Spodoptera; D018675:Toxicity Tests
chemical_list: D004338:Drug Combinations; D007306:Insecticides; D018942:Macrolides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; C415329:spinosad
keywords: Cytochrome C release; Mitochondrial dysfunction; Programmed cell death; Spinosad