Chemoproteomic Profiling of Acetanilide Herbicides Reveals Their Role in Inhibiting Fatty Acid Oxidation.

doi:10.1021/acschembio.6b01001

Paper

Chemoproteomic Profiling of Acetanilide Herbicides Reveals Their Role in Inhibiting Fatty Acid Oxidation.

Published Jan 20, 2017 · Jessica L. Counihan, Megan Duckering, Esha D. Dalvie

ACS chemical biology

Q1 SJR score

23

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0

Influential Citations

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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.

In Vitro Study

Study Snapshot

Acetanilide herbicides inhibit fatty acid oxidation, leading to increased free fatty acids, triglycerides, and cholesteryl esters in the liver.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Chemoproteomic Profiling of Acetanilide Herbicides Reveals Their Role in Inhibiting Fatty Acid Oxidation.

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References

Activity-based protein profiling for mapping and pharmacologically interrogating proteome-wide ligandable hotspots.

Activity-based protein profiling can map ligandable hotspots in proteomes, enabling the development of highly selective small-molecule inhibitors against disease-related protein targets.

Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation.

Hepatic fatty acid oxidation is essential for maintaining systemic energy balance during starvation by constraining adipocyte lipolysis and regulating systemic catabolism when glucose is limiting.

GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity.

GSTP1 inhibitors show potential as a novel therapeutic strategy for combating triple-negative breast cancer by impairing key cancer metabolism and signaling pathways.

Proteome-wide covalent ligand discovery in native biological systems

Fragment-based ligand discovery identifies small-molecule probes for difficult-to-target proteins, revealing protein functions and potential therapeutic targets in native biological systems.

Loss of Adipose Fatty Acid Oxidation Does Not Potentiate Obesity at Thermoneutrality.

Loss of adipose fatty acid oxidation does not increase obesity in mice when housed at thermoneutrality, despite cellular and physiological deficits in brown adipose tissue.

Citations

An in-depth analysis of the effects of excessive acetochlor exposure on chicken liver health

Excessive acetochlor exposure significantly disrupts chicken liver health, affecting liver function and highlighting the need for better herbicide risk assessment, pollution control, and sustainable agricultural practices.

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New iron regulatory system inhibitors, such as V004-0872, could help limit iron availability and oxidative stress in iron-overloaded diseases.

Ligand Modification-Free Methods for the Profiling of Protein-Environmental Chemical Interactions.

Ligand modification-free methods have been developed to effectively profile protein-environmental chemical interactions, aiding in toxicological mechanisms and health risk assessment.

Cellular Exposure to Chloroacetanilide Herbicides Induces Distinct Protein Destabilization Profiles

Cellular exposure to chloroacetanilide herbicides, such as acetochlor, alachlor, and propachlor, leads to distinct protein destabilization profiles, primarily affecting proteins with reactive cysteine residues.

The herbicide acetochlor causes lipid peroxidation by inhibition of glutathione peroxidase 4

Acetochlor, a common agricultural pesticide, disrupts lipid homeostasis by inhibiting glutathione peroxidase 4, leading to lipid peroxidation and metabolic disruption, potentially contributing to obesity in rural populations.

Ligandability of E3 Ligases for Targeted Protein Degradation Applications.

Chemoproteomics-enabled covalent screening strategies can discover new E3 ligase recruiters for targeted protein degradation, expanding the druggable proteome.

A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline

The novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease by impairing lysosomal function and facilitating amyloid- pathology and cognitive decline.