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

Ismail, Hanafy ORCID: https://orcid.org/0000-0002-9953-9588, O'Neill, Paul M, Hong, David W, Finn, Robert D, Henderson, Colin J, Wright, Aaron T, Cravatt, Benjamin F, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173 and Paine, Mark ORCID: https://orcid.org/0000-0003-2061-7713 (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, Vol 110, Issue 49, pp. 19766-19771.

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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
Subjects:	QU Biochemistry > Enzymes > QU 140 Oxidoreductases QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by) WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 190 Hemoglobin and other hemeproteins. Porphyrins (Associated with hemoglobin)
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.1320185110
Depositing User:	Samantha Sheldrake
Date Deposited:	10 Dec 2013 11:33
Last Modified:	06 Feb 2018 13:06
URI:	https://archive.lstmed.ac.uk/id/eprint/3497

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