A Drosophila systems approach to xenobiotic metabolism

Yang, J., McCart, C., Woods, D. J., Terhzaz, S. , Greenwood, K. G., Ffrench-Constant, R. H. and Dow, J. A.T. (2007) A Drosophila systems approach to xenobiotic metabolism. Physiological Genomics, 30(3), pp. 223-231. (doi:10.1152/physiolgenomics.00018.2007)

Yang, J., McCart, C., Woods, D. J., Terhzaz, S. , Greenwood, K. G., Ffrench-Constant, R. H. and Dow, J. A.T. (2007) A Drosophila systems approach to xenobiotic metabolism. Physiological Genomics, 30(3), pp. 223-231. (doi:10.1152/physiolgenomics.00018.2007)

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Abstract

Insecticide resistance is a major problem for both medicine and agriculture and is frequently associated with overexpression of metabolic enzymes that catalyze the breakdown of pesticides, leading to broad-spectrum resistance. However, the insect tissues within which these metabolic enzymes normally reside remain unclear. Microarray analysis of nine adult tissues from Drosophila melanogaster reveals that cytochrome P-450s and glutathione-S-transferases show highly tissue-specific expression patterns; most were confined to one or more epithelial tissues, and half showed dominant expression in a single tissue. The particular detoxifying enzymes encountered by a xenobiotic thus depend critically on the route of administration. In particular, known insecticide metabolism genes are highly enriched in insect Malpighian (renal) tubules, implicating them in xenobiotic metabolism. The tubules thus display, with the fat body, roles analogous to the vertebrate liver and immune system, as well as its acknowledged renal function. To illustrate this, when levels of a single gene, Cyp6g1, were manipulated in just the Malpighian tubules of adult Drosophila, the survival of the whole insect after 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) challenge was altered, whereas corresponding manipulations in the nervous system or the fat body were without effect. This shows that, although detoxification enzymes are widely distributed, baseline protection against DDT resides primarily in the insect excretory system, corresponding to less than 0.1% of the mass of the organism.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yang, Dr Jingli and Dow, Professor Julian and Terhzaz, Dr Selim
Authors: Yang, J., McCart, C., Woods, D. J., Terhzaz, S., Greenwood, K. G., Ffrench-Constant, R. H., and Dow, J. A.T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Physiological Genomics
ISSN:1094-8341
ISSN (Online):1531-2267
Published Online:08 May 2007

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
415661Spatiotemporal filtering in calcium control of mitochondrial functionJulian DowBiotechnology and Biological Sciences Research Council (BBSRC)BB/D013852/1Institute of Molecular Cell and Systems Biology
325421Affymetrix array service for the UK Drosophila CommunityJulian DowBiotechnology and Biological Sciences Research Council (BBSRC)G17767Institute of Molecular Cell and Systems Biology