Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein

Acrolein exists in common pollutants, such as cigarette smoke and car exhaust, which has been implicated with many pathological processes. It is also one type of endogenous lipid-derived electrophile (LDE) generated from lipid peroxidation when cells are under oxidative stress. Chemically, acrolein is able to covalently modify nucleophilic residues in proteins so as to influence their structures and functions, and identification of targets of acrolein modification in proteomes is critical for understanding its biological roles. Here, we report a quantitative chemoproteomic method to globally profile acrolein modifications using an aldehyde-directed aniline-based probe. Collectively, we identified >2300 proteins and >500 cysteine sites that are targeted by acrolein. Our data provide valuable information for understanding acrolein-mediated toxicity and expanding our knowledge of oxidative stress-mediated damage and signaling.