title: Abamectin resistance in Drosophila is related to increased expression of P-glycoprotein via the dEGFR and dAkt pathways.
abstract: Many insects have evolved resistance to abamectin but the mechanisms involved in this resistance have not been well characterized. P-glycoprotein (P-gp), an ATP-dependent drug-efflux pump transmembrane protein, may be involved in abamectin resistance. We investigated the role of P-gp in abamectin (ABM) resistance in Drosophila using an ABM-resistant strain developed in the laboratory. A toxicity assay, Western blotting analysis and a vanadate-sensitive ATPase activity assay all demonstrated the existence of a direct relationship between P-gp expression and ABM resistance in these flies. Our observations indicate that P-gp levels in flies' heads were higher than in their thorax and abdomen, and that both P-gp levels and LC(50) values were higher in resistant than in susceptible and P-gp-deficient strains. In addition, P-gp levels in the blood-brain barrier (BBB) of resistant flies were higher than in susceptible and P-gp-deficient flies, which is further evidence that a high level of P-gp in the BBB is related to ABM resistance. Furthermore, we found greater expression of Drosophila EGFR (dEGFR) in the resistant strain than in the susceptible strain, and that the level of Drosophila Akt (dAkt) was much higher in resistant than in susceptible flies, whereas that in P-gp-deficient flies was very low. Compared to susceptible flies, P-gp levels in the resistant strain were markedly suppressed by the dEGFR and dAkt inhibitors lapatinib and wortmannin. These results suggest that the increased P-gp in resistant flies was regulated by the dEGFR and dAkt pathways and that increased expression of P-gp is an important component of ABM resistance in insects.
authors: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors: Liang
authors: L
authors: Luo
authors: Ying-Jian
authors: YJ
authors: Sun
authors: Yi-Jun
authors: YJ
authors: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides / Q000633:toxicity; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D018010:Receptors, Invertebrate Peptide / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D029721:Drosophila Proteins; D007306:Insecticides; D018010:Receptors, Invertebrate Peptide; C048324:abamectin; D007559:Ivermectin; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Avermectin; Drosophila; EGFR; Resistance