Dataset Information

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

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 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.

SUBMITTER: Na AY

PROVIDER: S-EPMC8395202 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Na Ann-Yae AY Paudel Sanjita S Choi Soyoung S Lee Jun Hyung JH Kim Min-Sik MS Bae Jong-Sup JS Lee Sangkyu S

International journal of molecular sciences 20210808 16

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 ...[more]

PMID: 34445236

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Project description:Lysine acetylation is a highly conserved posttranslational modification that plays essential roles in multiple biological functions in a variety of organisms. Deinococcus radiodurans (D. radiodurans) is famous for its extreme resistance to radiation. However, few studies have focused on the lysine acetylation in D. radiodurans. In the present study, antibody enrichment technology and high-resolution liquid chromatography mass spectrometry are used to perform a global analysis of lysine acetylation of D. radiodurans. We create the largest acetylome data set in D. radiodurans to date, totally identifying 4,364 lysine acetylation sites on 1,410 acetylated proteins. Strikingly, of the 3,085 proteins annotated by the uniport database, 45.7% of proteins are acetylated in D. radiodurans. In particular, the glutamate (G) preferentially appears at the -1 and +1 positions of acetylated lysine residues by motif analysis. The acetylated proteins are involved in metabolic pathways, propanoate metabolism, carbon metabolism, fatty acid metabolism, and the tricarboxylic acid cycle. Protein-protein interaction networks demonstrate that four clusters are involved in DNA damage repair, including homologous recombination, mismatch repair, nucleotide excision repair, and base excision repair, which suggests that acetylation plays an indispensable role in the extraordinary capacity to survive high levels of ionizing radiation. Taken together, we report the most comprehensive lysine acetylation in D. radiodurans for the first time, which is of great significance to reveal its robust resistance to radiation. IMPORTANCE D. radiodurans is distinguished by the most radioresistant organism identified to date. Lysine acetylation is a highly conserved posttranslational modification that plays an essential role in the regulation of many cellular processes and may contribute to its extraordinary radioresistance. We integrate acetyl-lysine enrichment strategy, high-resolution mass spectrometry, and bioinformatics to profile the lysine acetylated proteins for the first time. It is striking that almost half of the total annotated proteins are identified as acetylated forms, which is the largest acetylome data set reported in D. radiodurans to date. The acetylated proteins are involved in metabolic pathways, propanoate metabolism, carbon metabolism, fatty acid metabolism, and the tricarboxylic acid cycle. The results of this study reinforce the notion that acetylation plays critical regulatory roles in diverse aspects of the cellular process, especially in DNA damage repair and metabolism. It provides insight into the roles of lysine acetylation in the robust resistance to radiation.

Dataset Information

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

Publications

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

Similar Datasets

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