Integrative Profiling of Lysine Acylome in Sepsis-Induced Liver Injury

Sepsis is one of the life-threatening diseases worldwide.Despitethe continuous progress in medicine, the specific mechanism of sepsisremains unclear. A key strategy of pathogens is to use post-translationalmodification to modulate host factors critical for infection. We employedglobal immunoprecipitation technology for lysine acetylation (Kac),succinylation (Ksu), and malonylation (Kmal) for the first globallysine acylation (Kacy) analysis in a cecum ligation and puncture(CLP) model in mouse. This was performed to reveal the pathogenicmechanism of integrative Kacy and the changes in modification sites.In total, 2230 sites of 1,235 Kac proteins, 1,887 sites of 433 Ksuproteins, and 499 sites of 276 Kmal proteins were quantified and normalizedby their protein levels. We focused on 379 sites in 219 upregulatedproteins as the integrative Kacy sites of Kac, Ksu, and Kmal on thebasis of sirtuins decreased in the CLP group. KEGG pathway analysisof integrative Kacy in 219 upregulated proteins revealed three centralmetabolic pathways: glycolysis/gluconeogenesis, pyruvate metabolism,and tricarboxylic acid cycle. These findings reveal the key pathogenicmechanism of integrative PTM alteration in terms of the decreasedsirtuins level and provide an important foundation for an in-depthstudy of the biological function of Kacy in sepsis.