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

Selim Terhzaz; Pablo Cabrero; Robert A. Brinzer; Kenneth Agerlin Halberg; Julian A T Dow; Shireen-A Davies

doi:10.1016/j.ibmb.2015.06.002

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

Selim Terhzaz, Pablo Cabrero, Robert A. Brinzer, Kenneth Agerlin Halberg, Julian A T Dow, Shireen-A Davies

34 Citations (Scopus)

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.

Original language	English
Journal	Insect Biochemistry and Molecular Biology
Volume	67
Pages (from-to)	38-46
Number of pages	9
ISSN	0965-1748
DOIs	https://doi.org/10.1016/j.ibmb.2015.06.002
Publication status	Published - 1 Dec 2015
Externally published	Yes

Keywords

Faculty of Science

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16. Terhzaz et al., 2015Final published version, 1.58 MB

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title = "A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance",

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.",

keywords = "Faculty of Science, Drosophila, Insecticide resistance",

author = "Selim Terhzaz and Pablo Cabrero and Brinzer, {Robert A.} and Halberg, {Kenneth Agerlin} and Dow, {Julian A T} and Shireen-A Davies",

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T1 - A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance

AU - Terhzaz, Selim

AU - Cabrero, Pablo

AU - Brinzer, Robert A.

AU - Halberg, Kenneth Agerlin

AU - Dow, Julian A T

AU - Davies, Shireen-A

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - Drosophila

KW - Insecticide resistance

U2 - 10.1016/j.ibmb.2015.06.002

DO - 10.1016/j.ibmb.2015.06.002

M3 - Journal article

C2 - 26073628

SN - 0965-1748

VL - 67

SP - 38

EP - 46

JO - Insect Biochemistry and Molecular Biology

JF - Insect Biochemistry and Molecular Biology

ER -

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

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