The molecular action of the novel insecticide, Pyridalyl

• Published in: Insect biochemistry and molecular biology Vol. 41; no. 7; pp. 459 - 469
• Main Authors: Powell, Gerard F., Ward, Deborah A., Prescott, Mark C., Spiller, David G., White, Michael R.H., Turner, Phillip C., Earley, Fergus G.P., Phillips, Janet, Rees, Huw H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2011
• Subjects: Animals; apoptosis; Bombyx; Bombyx mori; Cell Culture Techniques; Cell Death - drug effects; Cell Line; cytochrome P-450; Cytochrome P-450 Enzyme System - metabolism; cytotoxicity; gene expression regulation; glyceraldehyde-3-phosphate dehydrogenase; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Insect Control - methods; Insect Proteins - genetics; Insect Proteins - metabolism; insecticidal properties; Insecticide; Insecticide Resistance; insecticides; Insecticides - pharmacology; Larva; larvae; Lepidoptera; metabolism; midgut; Molecular action; peroxiredoxin; Peroxiredoxins - genetics; Peroxiredoxins - metabolism; Phenyl Ethers - pharmacology; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - metabolism; protein degradation; proteome; Proteome - genetics; Proteome - metabolism; Proteomics; Pyridalyl; reactive oxygen species; Reactive Oxygen Species - metabolism; ROS; Spodoptera - cytology; Spodoptera - drug effects; Spodoptera frugiperda; Thysanoptera; Up-Regulation; Pyridalyl; Molecular action; Insecticide; Lepidoptera; Proteomics; ROS; TPx; GAPDH
• ISSN: 0965-1748; 1879-0240
• DOI: 10.1016/j.ibmb.2011.03.007

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. Investigation of involvement of cytochrome P450s and of apoptosis, together with proteomic analysis of Pyridalyl (PAL)-resistant and –susceptible Spodopterafrugiperda Sf21 cells and of proteomes from Bombyx tissues following PAL treatment, led to a hypothesis of PAL action. [Display omitted] ► Pyridalyl (insecticide) action requires cytochrome P450 activity and does not involve apoptosis. ► Thiol peroxiredoxin is up-regulated in Pyridalyl-resistant cells. ► Pyridalyl leads to up-regulation of proteasome subunits in Bombyx cells/larvae. ► A hypothesis for Pyridalyl action involves P450, ROS, and proteasome activity.