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.