A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance

Terhzaz, S. , Cabrero, P. , Brinzer, R. A., Halberg, K. A., Dow, J. A.T. and Davies, S.-A. (2015) A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance. Insect Biochemistry and Molecular Biology, (doi:10.1016/j.ibmb.2015.06.002) (PMID:26073628) (PMCID:PMC4673087)

Terhzaz, S. , Cabrero, P. , Brinzer, R. A., Halberg, K. A., Dow, J. A.T. and Davies, S.-A. (2015) A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance. Insect Biochemistry and Molecular Biology, (doi:10.1016/j.ibmb.2015.06.002) (PMID:26073628) (PMCID:PMC4673087)

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Abstract

The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila melanogaster Malpighian (renal) tubules are critical organs in the detoxification and elimination of these foreign compounds, so the tubule response induced by dietary exposure to the insecticide permethrin was examined. We found that expression of the gene encoding Cytochrome P450-4e3 (Cyp4e3) is significantly up-regulated by Drosophila fed on permethrin and that manipulation of Cyp4e3 levels, specifically in the principal cells of the Malpighian tubules, impacts significantly on the survival of permethrin-fed flies. Both dietary exposure to permethrin and Cyp4e3 knockdown cause a significant elevation of oxidative stress-associated markers in the tubules, including H2O2 and lipid peroxidation byproduct, HNE (4-hydroxynonenal). Thus, Cyp4e3 may play an important role in regulating H2O2 levels in the endoplasmic reticulum (ER) where it resides, and its absence triggers a JAK/STAT and NF-κB-mediated stress response, similar to that observed in cells under ER stress. This work increases our understanding of the molecular mechanisms of insecticide detoxification and provides further evidence of the oxidative stress responses induced by permethrin metabolism.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cabrero, Mr Pablo and Dow, Professor Julian and Terhzaz, Dr Selim and Davies, Professor Shireen and Halberg, Dr Kenneth
Authors: Terhzaz, S., Cabrero, P., Brinzer, R. A., Halberg, K. A., Dow, J. A.T., and Davies, S.-A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Insect Biochemistry and Molecular Biology
Publisher:Elsevier Ltd.
ISSN:0965-1748
ISSN (Online):1879-0240
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Insect Biochemistry and Molecular Biology 2015
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
503711Epithelial stress sensors: novel roles for cytochrome P450s and organellar calcium in integrated stress and immune responses.Shireen DaviesBiotechnology and Biological Sciences Research Council (BBSRC)BB/G020620/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
626691Functional Genomics of the enigmatic stellate cell.Shireen DaviesBiotechnology and Biological Sciences Research Council (BBSRC)BB/L002647/1RI MOLECULAR CELL & SYSTEMS BIOLOGY