Constitutive activation of the Nrf2/Keap1 pathway in insecticide-resistant strains of Drosophila
| Autor: | Geanette Lam, Jyoti R. Misra, Carl S. Thummel |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Insecticides
Pesticide resistance Biochemistry Article Insecticide Resistance Transcriptional regulation Animals Drosophila Proteins Humans Promoter Regions Genetic Molecular Biology Gene Regulation of gene expression Genetics Binding Sites Kelch-Like ECH-Associated Protein 1 biology Microarray analysis techniques Intracellular Signaling Peptides and Proteins biology.organism_classification Oxidative Stress Drosophila melanogaster Gene Expression Regulation Insect Science Inactivation Metabolic Signal transduction Drosophila Protein Protein Binding Signal Transduction |
| Zdroj: | Insect Biochemistry and Molecular Biology. 43:1116-1124 |
| ISSN: | 0965-1748 |
| Popis: | Pesticide resistance poses a major challenge for the control of vector-borne human diseases and agricultural crop protection. Although a number of studies have defined how mutations in specific target proteins can lead to insecticide resistance, much less is known about the mechanisms by which constitutive overexpression of detoxifying enzymes contributes to metabolic pesticide resistance. Here we show that the Nrf2/Keap1 pathway is constitutively active in two laboratory-selected DDT-resistant strains of Drosophila, 91R and RDDTR, leading to the overexpression of multiple detoxifying genes. Disruption of the Drosophila Nrf2 ortholog, CncC, or overexpression of Keap1, is sufficient to block this transcriptional response. In addition, a CncC-responsive reporter is highly active in both DDT-resistant strains and this response is dependent on the presence of an intact CncC binding site in the promoter. Microarray analysis revealed that ∼20% of the genes differentially expressed in the 91R strain are known CncC target genes. Finally, we show that CncC is partially active in these strains, consistent with the fitness cost associated with constitutive activation of the pathway. This study demonstrates that the Nrf2/Keap1 pathway contributes to the widespread overexpression of detoxification genes in insecticide-resistant strains and raises the possibility that inhibitors of this pathway could provide effective synergists for insect population control. |
| Databáze: | OpenAIRE |
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