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

Hanafy M. Ismail, Paul M. O'Neill, David W. Hong, Robert D. Finn, Colin J. Henderson, Aaron T. Wright, Benjamin F. Cravatt, Janet Hemingway (Lead / Corresponding author), Mark J. I. Paine (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    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 b(5) 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.
    Original languageEnglish
    Pages (from-to)19766-19771
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume110
    Issue number49
    DOIs
    Publication statusPublished - 3 Dec 2013

    Fingerprint

    Pyrethrins
    Insecticides
    Cytochrome P-450 Enzyme System
    Enzymes
    Glucuronosyltransferase
    Cytochromes b
    Arthropods
    Liver Microsomes
    Microsomes
    Culicidae
    Knockout Mice
    Rodentia
    Oxidoreductases
    Pharmacology
    Liver

    Cite this

    Ismail, Hanafy M. ; O'Neill, Paul M. ; Hong, David W. ; Finn, Robert D. ; Henderson, Colin J. ; Wright, Aaron T. ; Cravatt, Benjamin F. ; Hemingway, Janet ; Paine, Mark J. I. / Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 49. pp. 19766-19771.
    @article{b6ddca46188e446d9d6be43296aed87e,
    title = "Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions",
    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 b(5) 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.",
    author = "Ismail, {Hanafy M.} and O'Neill, {Paul M.} and Hong, {David W.} and Finn, {Robert D.} and Henderson, {Colin J.} and Wright, {Aaron T.} and Cravatt, {Benjamin F.} and Janet Hemingway and Paine, {Mark J. I.}",
    year = "2013",
    month = "12",
    day = "3",
    doi = "10.1073/pnas.1320185110",
    language = "English",
    volume = "110",
    pages = "19766--19771",
    journal = "Proceedings of the National Academy of Sciences",
    issn = "0027-8424",
    publisher = "National Academy of Sciences",
    number = "49",

    }

    Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions. / Ismail, Hanafy M.; O'Neill, Paul M.; Hong, David W.; Finn, Robert D.; Henderson, Colin J.; Wright, Aaron T.; Cravatt, Benjamin F.; Hemingway, Janet (Lead / Corresponding author); Paine, Mark J. I. (Lead / Corresponding author).

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 49, 03.12.2013, p. 19766-19771.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions

    AU - Ismail, Hanafy M.

    AU - O'Neill, Paul M.

    AU - Hong, David W.

    AU - Finn, Robert D.

    AU - Henderson, Colin J.

    AU - Wright, Aaron T.

    AU - Cravatt, Benjamin F.

    AU - Hemingway, Janet

    AU - Paine, Mark J. I.

    PY - 2013/12/3

    Y1 - 2013/12/3

    N2 - 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 b(5) 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.

    AB - 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 b(5) 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.

    U2 - 10.1073/pnas.1320185110

    DO - 10.1073/pnas.1320185110

    M3 - Article

    C2 - 24248381

    VL - 110

    SP - 19766

    EP - 19771

    JO - Proceedings of the National Academy of Sciences

    JF - Proceedings of the National Academy of Sciences

    SN - 0027-8424

    IS - 49

    ER -