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Anopheles gambiae P450 reductase is highly expressed in oenocytes and in vivo knockdown increases permethrin susceptibility
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Insect Molecular Biology
Yazar(lar) :
G. J. Lycett , L. A. McLaughlin , H. Ranson , J. Hemingway , F. C. Kafatos , T. G. Loukeris , M. J. I. Paine
Konu :
Insect Science, Genetics, Molecular Biology
Yıl :
2006
L. A. McLaughlin
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
We describe an in vivo model for investigation of detoxification mechanisms of the mosquito Anopheles gambiae, important for the development of malaria control programmes. Cytochrome P450s are involved in metabolic insecticide resistance and require NADPH cytochrome P450 reductase (CPR) to function. Here we demonstrate that the major sites of adult mosquito CPR expression are oenocytes, mid‐gut epithelia and head appendages. High CPR expression was also evident in Drosophila oenocytes indicating a general functional role in these insect cells. RNAi mediated knockdown drastically reduced CPR expression in oenocytes, and to a lesser extent in mid‐gut epithelia; the head was unaffected. These flies showed enhanced sensitivity to permethrin, demonstrating a key role for abdominal/mid‐gut P450s in pyrethroid metabolism, aiding the development of insecticides.
DOI : 10.1111/j.1365-2583.2006.00647.x
ISSN: 0962-1075
Sayı: 3
Cilt: 15
Sayfa: 321-327
2
Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Insect Molecular Biology
Yazar(lar) :
L. A. Mclaughlin , U. Niazi , J. Bibby , J.-P. David , J. Vontas , J. Hemingway , H. Ranson , M. J. Sutcliffe , M. J. I. Paine
Konu :
Insect Science, Genetics, Molecular Biology
Yıl :
2008
L. A. Mclaughlin
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Kaydet Alıntıla
Three CYP6Z genes are linked to a major pyrethroid resistance locus in the mosquito Anopheles gambiae. We have expressed CYP6Z2 in Escherichia coli and produced a structural model in order to examine its role in detoxification. E. coli membranes co‐expressing CYP6Z2 and An. gambiae P450 reductase (AgCPR) catalysed the dealkylation of benzyloxyresorufin with kinetic parameters Km = 0.13 µM; Kcat = 1.5 min‐1. The IC50 values of a wide range of compounds were measured. Pyrethroids cypermethrin and permethrin produced low IC50 values, but were not metabolized. Plant flavanoids were the most potent inhibitors. Several compounds were shown to be substrates, suggesting that CYP6Z2 has broad substrate specificity and plays an important chemo‐protective role during the herbivorous phase of the life‐cycle.
DOI : 10.1111/j.1365-2583.2007.00788.x
ISSN: 0962-1075
Sayı: 2
Cilt: 17
Sayfa: 125-135

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