title: The molecular action of the novel insecticide, Pyridalyl.
abstract: Pyridalyl is a recently discovered insecticide that exhibits high insecticidal activity against Lepidoptera and Thysanoptera. Pyridalyl action requires cytochrome P450 activity, possibly for production of a bioactive derivative, Pyridalyl metabolism being prevented by general P450 inhibitors. Apoptosis is apparently not involved in the cytotoxicity. Continuous culture of Spodoptera frugiperda Sf21 cells in sub-lethal doses of Pyridalyl, results in a Pyridalyl-resistant cell line. Probing the molecular action of Pyridalyl by comparison of the proteomes of Pyridalyl-resistant and -susceptible cell lines, revealed differential expression of a number of proteins, including the up-regulation of thiol peroxiredoxin (TPx), in the resistant cells. Treatment of Bombyx mori larvae with Pyridalyl, followed by comparison of the midgut microsomal sub-proteome, revealed the up-regulation of three proteasome subunits. Such subunits, together with Hsp70 stress proteins, glyceraldehyde 3-phosphate dehydrogenases (GAPDHs) and thiol peroxiredoxin (TPx) were also up-regulated in the whole proteome of B. mori BM36 cells following treatment with the insecticide. The foregoing results lead to the hypothesis that cytochrome P450 action leads to an active Pyridalyl metabolite, which results in production of reactive oxygen species (ROS), that leads to damage to cellular macromolecules (e.g., proteins) and enhanced proteasome activity leads to increased protein degradation and necrotic cell death.
authors.affiliation: School of Biological Sciences, The University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Powell
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ward
authors.forename: Mark C
authors.initials: MC
authors.lastname: Prescott
authors.forename: David G
authors.initials: DG
authors.lastname: Spiller
authors.forename: Michael R H
authors.initials: MR
authors.lastname: White
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Turner
authors.forename: Fergus G P
authors.initials: FG
authors.lastname: Earley
authors.forename: Janet
authors.initials: J
authors.lastname: Phillips
authors.forename: Huw H
authors.initials: HH
authors.lastname: Rees
mesh_terms: D000818:Animals; D012831:Bombyx; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007300:Insect Control / Q000379:methods; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D007814:Larva; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D010647:Phenyl Ethers / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D018840:HSP70 Heat-Shock Proteins; D019476:Insect Proteins; D007306:Insecticides; D010647:Phenyl Ethers; D020543:Proteome; D017382:Reactive Oxygen Species; D003577:Cytochrome P-450 Enzyme System; D054464:Peroxiredoxins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D046988:Proteasome Endopeptidase Complex; C418569:S 1812