College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
J Proteome Res. 2023 Dec 1;22(12):3683-3691. doi: 10.1021/acs.jproteome.3c00156. Epub 2023 Oct 28.
Among the various cell types that constitute the liver, Kupffer cells (KCs) are responsible for the elimination of gut-derived foreign products. Protein lysine acetylation (Kac) and lactylation (Kla) are dynamic and reversible post-translational modifications, and various global acylome studies have been conducted for liver and liver-derived cells. However, no such studies have been conducted on KCs. In this study, we identified 2198 Kac sites in 925 acetylated proteins and 289 Kla sites in 181 lactylated proteins in immortalized mouse KCs using global acylome technology. The subcellular distributions of proteins with Kac and Kla site modifications differed. Similarly, the specific sequence motifs surrounding acetylated or lactylated lysine residues also showed differences. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to better understand the differentially expressed proteins in the studies by Kac and Kla. In the newly identified Kla, we found K82 lactylation in the high-mobility group box-1 protein in the neutrophil extracellular trap formation category using KEGG enrichment analyses. Here, we report the first proteomic survey of Kac and Kla in KCs.
在构成肝脏的各种细胞类型中，库普弗细胞（KCs）负责清除肠道来源的外来产物。蛋白赖氨酸乙酰化（Kac）和乳酰化（Kla）是动态和可逆的翻译后修饰，已经对肝脏和肝源性细胞进行了各种全局酰基组研究。然而，在 KCs 中尚未进行此类研究。在这项研究中，我们使用全局酰基组技术在永生化的小鼠 KCs 中鉴定了 925 个乙酰化蛋白中的 2198 个 Kac 位点和 181 个乳酰化蛋白中的 289 个 Kla 位点。具有 Kac 和 Kla 位点修饰的蛋白质的亚细胞分布不同。同样，围绕乙酰化或乳酰化赖氨酸残基的特定序列基序也显示出差异。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，以更好地理解 Kac 和 Kla 研究中的差异表达蛋白。在新鉴定的 Kla 中，我们使用 KEGG 富集分析在中性粒细胞胞外诱捕网形成类别中发现了高迁移率族框-1 蛋白中的 K82 乳酰化。在这里，我们报告了 KCs 中 Kac 和 Kla 的首次蛋白质组学调查。
