Integrative Profiling of Lysine Acylome in Sepsis-Induced Liver Injury

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