Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions

Ismail, Hanafy, O'Neill, Paul, Hong, David, Finn, Robert, Henderson, Colin, Wright, Aaron, Cravatt, Benjamin, Hemingway, Janet and Paine, Mark (2013) Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions. Proceedings of the National Academy of Sciences of the United States of America, 110 (49). pp. 19766-19771. ISSN 0027-8424

[img]
Preview
PDF (Article freely available through PNAS open access option)
PNAS-2013-Ismail-19766-71.pdf - Published Version

Download (861kB) | Preview
Official URL: http://dx.doi.org/10.1073/pnas.1320185110

Abstract

Pyrethroid insecticides are used to control diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid-metabolizing and nonmetabolizing mosquito P450s, as well as rodent microsomes, to measure labeling specificity, plus cytochrome P450 oxidoreductase and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using PyABPs, we were able to profile active enzymes in rat liver microsomes and identify pyrethroid-metabolizing enzymes in the target tissue. These included P450s as well as related detoxification enzymes, notably UDP-glucuronosyltransferases, suggesting a network of associated pyrethroid-metabolizing enzymes, or “pyrethrome.” Considering the central role P450s play in metabolizing insecticides, we anticipate that PyABPs will aid in the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450–insecticide interactions and aiding the development of unique tools for disease control.

Item Type: Article
Additional Information: Published online before print.
Uncontrolled Keywords: insecticide resistance, drug metabolism, interactome, malaria
Subjects: C900 Others in Biological Sciences
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: Ay Okpokam
Date Deposited: 21 Nov 2013 17:16
Last Modified: 12 May 2017 04:59
URI: http://nrl.northumbria.ac.uk/id/eprint/14690

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics


Policies: NRL Policies | NRL University Deposit Policy | NRL Deposit Licence