TitleBenzo[ a]pyrene Induction of Glutathione S-Transferases: An Activity-Based Protein Profiling Investigation.
Publication TypeJournal Article
Year of Publication2019
AuthorsStoddard, EG, Killinger, BJ, Nag, S, Martin, J, Corley, RA, Smith, JN, Wright, AT
JournalChem Res Toxicol
Volume32
Issue6
Pagination1259-1267
Date Published2019 06 17
ISSN1520-5010
KeywordsAnimals, Benzo(a)pyrene, Enzyme Induction, Female, Glutathione Transferase, Liver, Mice, Mice, Inbred Strains, Molecular Probes, Molecular Structure, Proteomics, RNA, Messenger
Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated from combustion of carbon-based matter. Upon ingestion, these molecules can be bioactivated by cytochrome P450 monooxygenases to oxidized toxic metabolites. Some of these metabolites are potent carcinogens that can form irreversible adducts with DNA and other biological macromolecules. Conjugative enzymes, such as glutathione S-transferases or UDP-glucuronosyltransferases, are responsible for the detoxification and/or facilitate the elimination of these carcinogens. While responses to PAH exposures have been extensively studied for the bioactivating cytochrome P450 enzymes, much less is known regarding the response of glutathione S-transferases in mammalian systems. In this study, we investigated the expression and activity responses of murine hepatic glutathione S-transferases to benzo[ a]pyrene exposure using global proteomics and activity-based protein profiling for chemoproteomics, respectively. Using this approach, we identified several enzymes exhibiting increased activity including GSTA2, M1, M2, M4, M6, and P1. The activity of one GST enzyme, GSTA4, was found to be downregulated with increasing B[ a]P dose. Activity responses of several of these enzymes were identified as being expression-independent when comparing global and activity-based data sets, possibly alluding to as of yet unknown regulatory post-translational mechanisms.

DOI10.1021/acs.chemrestox.9b00069
Alternate JournalChem Res Toxicol
PubMed ID30938511
PubMed Central IDPMC7138413
Grant ListP41 GM103493 / GM / NIGMS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States