Acrolein is a universal contaminant with high nucleophilicity in environment and also an endogenous product from lipid peroxidation or polyamine metabolism. Acrolein can react with nucleophilic amino acids, such as cysteines, lysines and histidines via Michael addition. Also, Schiff base products can be formed between acrolein and free amine of lysines. Accumulating evidences demonstrated that acrolein is involved in many diseases, including Alzheimer's disease (AD). Previously we found that oral exposure of acrolein induced AD-like pathology in rats. Here we investigated the acrolein-conjugated proteins in the hippocampus of acrolein-treated mice (3.0 mg/kg/d by gavage for 4 weeks) and aged APP/PS1 mice (the age of 22 months). Acrolein-conjugated proteins were enriched by an aniline-based aldehyde-directed probe, meta-aminophenylacetylene (m-APA). Combined with a quantitative chemoproteomic strategy, 912 proteins were finally identified. Gene ontology analysis revealed several acrolein affected pathways including glycolysis, tricarboxylic acid (TCA) cycle and carbon metabolism. Acrolein are mainly conjugated with 14-3-3 protein and members of small GTPase family in hippocampus. Taken together, our results provide new evidences for the roles of acrolein in AD.
Keywords: 14-3-3 protein; Acrolein-conjugated protein; Alzheimer’s disease; Chemoproteomics; Protein modification.
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