title: Chemoproteomic Profiling of Acetanilide Herbicides Reveals Their Role in Inhibiting Fatty Acid Oxidation.
abstract: Acetanilide herbicides are among the most widely used pesticides in the United States, but their toxicological potential and mechanisms remain poorly understood. Here, we have used chemoproteomic platforms to map proteome-wide cysteine reactivity of acetochlor (AC), the most widely used acetanilide herbicide, in vivo in mice. We show that AC directly reacts with >20 protein targets in vivo in mouse liver, including the catalytic cysteines of several thiolase enzymes involved in mitochondrial and peroxisomal fatty acid oxidation. We show that the fatty acids that are not oxidized, due to impaired fatty acid oxidation, are instead diverted into other lipid pathways, resulting in heightened free fatty acids, triglycerides, cholesteryl esters, and other lipid species in the liver. Our findings show the utility of chemoproteomic approaches for identifying novel mechanisms of toxicity associated with environmental chemicals like acetanilide herbicides.
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Counihan
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Duckering
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Esha
authors.initials: E
authors.lastname: Dalvie
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Wan-Min
authors.initials: WM
authors.lastname: Ku
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Bateman
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Fisher
authors.affiliation: Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, 127 Morgan Hall, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Daniel K
authors.identifier: 0000-0003-1614-8360
authors.initials: DK
authors.lastname: Nomura
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D002853:Chromatography, Liquid; D005227:Fatty Acids / Q000378:metabolism*; D056945:Hep G2 Cells; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D020543:Proteome; D053719:Tandem Mass Spectrometry
chemical_list: D000083:Acetanilides; D005227:Fatty Acids; D006540:Herbicides; D020543:Proteome; C508827:acetanilide