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Article

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

1
BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea
2
Department of New Biology, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988, Korea
*
Author to whom correspondence should be addressed.
Academic Editors: Guido R. M. M. Haenen and Narasimham L. Parinandi
Int. J. Mol. Sci. 2021, 22(16), 8529; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168529
Received: 17 June 2021 / Revised: 29 July 2021 / Accepted: 5 August 2021 / Published: 8 August 2021
(This article belongs to the Collection Feature Papers in Molecular Toxicology)
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 hyperacetylation 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/gluconeogenesis 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. View Full-Text
Keywords: sepsis-induced liver dysfunction; hyperacetylation; SIRT; lysine acetylation; pyruvate kinase M2 sepsis-induced liver dysfunction; hyperacetylation; SIRT; lysine acetylation; pyruvate kinase M2
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MDPI and ACS Style

Na, A.-Y.; Paudel, S.; Choi, S.; Lee, J.H.; Kim, M.-S.; Bae, J.-S.; Lee, S. Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis. Int. J. Mol. Sci. 2021, 22, 8529. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168529

AMA Style

Na A-Y, Paudel S, Choi S, Lee JH, Kim M-S, Bae J-S, Lee S. Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis. International Journal of Molecular Sciences. 2021; 22(16):8529. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168529

Chicago/Turabian Style

Na, Ann-Yae, Sanjita Paudel, Soyoung Choi, Jun H. Lee, Min-Sik Kim, Jong-Sup Bae, and Sangkyu Lee. 2021. "Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis" International Journal of Molecular Sciences 22, no. 16: 8529. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168529

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