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Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

Title
Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis
Authors
Na, Ann-YaePaudel, SanjitaChoi, SoyoungLee, Jun HyungKim, Min-SikBae, Jong-SupLee, Sangkyu
DGIST Authors
Na, Ann-Yae; Paudel, Sanjita; Choi, Soyoung; Lee, Jun Hyung; Kim, Min-Sik; Bae, Jong-Sup; Lee, Sangkyu
Issue Date
2021-08
Citation
International Journal of Molecular Sciences, 22(16)
Type
Article
Article Type
Article
Author Keywords
HyperacetylationLysine acetylationPyruvate kinase M2Sepsis-induced liver dysfunctionSIRT
Keywords
SYSTEMIC INFLAMMATIONINHIBITIONLIVERSIRT5SHOCK
ISSN
1661-6596
Abstract
Sepsis-induced liver dysfunction (SILD) is a common event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification and diseases is challenging. We studied the relationship among lysine acetylation (Kac), sirtuin (SIRTs), and the factors involved in SILD, which was induced in LPS-stimulated HepG2 cells. Protein hy-peracetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1449 Kac sites based on comparative acetylome analysis and quantified 1086 Kac sites on 410 proteins for acetylation. Interestingly, the upregulated Kac proteins are enriched in glycolysis/glu-coneogenesis pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed at three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, consequently increasing the lactate concentration. In conclusion, this study is the first to conduct global profiling of Kac, suggesting that the Kac mechanism of PKM2 in glycolysis is associated with sepsis. Moreover, it helps to further understand the systematic information regarding hyperacetylation during the sepsis process. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
URI
http://hdl.handle.net/20.500.11750/14004
SYSTEMIC INFLAMMATION;INHIBITION;LIVER;SIRT5;SHOCK
DOI
10.3390/ijms22168529
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Related Researcher
  • Author Kim, Min-Sik Laboratory for QBIO and Precision Medicine
  • Research Interests Cancer Proteogenomics, Biomarker Discovery, Integrative Multi-Omics
Files:
Collection:
Department of New BiologyLaboratory for QBIO and Precision Medicine1. Journal Articles


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