Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identifies Hyperacetylation of PKM2 as a Metabolic Reg-ulator in Sepsis

ABSTRACT: Sepsis-induced liver dysfunction is a frequent event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification (PTM) and diseases is challenging. We studied the relationship among the lysine acetylation (Kac), the sirtuin (SIRTs), and their interactors carefully selected in sepsis-induced liver dysfunction (SILD), per-formed on LPS-stimulated HepG2 cells. Protein hyperacetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1,449 Kac sites based on comparative acetylome analysis, and quantified 1,086 Kac sites on 410 proteins for acetylation. Interestingly, the up-regulated Kac proteins are enriched in glycolysis/gluconeogenesis pathways in the KEGG category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed in three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, increasing the lactate concentration as a result. In conclusion, this study is the first to conduct global profiling of Kac, suggesting the Kac mecha-nism of PKM2 in glycolysis of sepsis. Moreover, it helps further understand the systematical in-formation of hyperacetylation during the sepsis process.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte

DISEASE(S): Bacterial Sepsis

SUBMITTER: Ann-Yae Na  

LAB HEAD: Sangkyu lee

PROVIDER: PXD027496 | Pride | 2024-01-30

REPOSITORIES: Pride