The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, China.
The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, China; Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, China.
J Proteomics. 2022 Jun 30;262:104597. doi: 10.1016/j.jprot.2022.104597. Epub 2022 Apr 27.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology in which the posttranslational modifications (PTMs) of proteins play an important role. PTMs, such as those involved in the formation of neutrophil extracellular traps (NETs), have been well studied. The excessive formation and release of NETs can mediate inflammation and joint destruction in RA. It has been gradually recognized that lysine malonylation (Kmal) can regulate some biological processes in some prokaryotes and eukaryotes. However, less is known about the role of Kmal in RA. We therefore performed proteome and malonylome analyses to explore the proteomic characteristics of the peripheral blood mononuclear cells from 36 RA patients and 82 healthy subjects. In total, 938 differentially expressed proteins (DEPs) and 42 differentially malonylated proteins (DMPs) with 55 Kmal sites were detected through a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis. Functional analysis showed that two DEPs with four malonylated sites and one DMP with a malonylated site were identified in the neutrophil extracellular trap formation (NETosis) pathway. Altogether, this study not only describes the characteristics of the malonylome in RA for the first time, but it also reveals that malonylation may be involved in the NETosis pathway. SIGNIFICANCE: This is the first report that reveals the proteomic features of Kmal in RA through a LC-MS/MS-based method. In this study, we found that several key DMPs were associated with the NETosis pathway, which contributes to the development of RA. The present results provide an informative dataset for the future exploration of Kmal in RA.
类风湿关节炎（RA）是一种病因不明的自身免疫性炎症性疾病，其中蛋白质的翻译后修饰（PTMs）起着重要作用。翻译后修饰，如涉及中性粒细胞胞外陷阱（NETs）形成的翻译后修饰，已经得到了很好的研究。NETs 的过度形成和释放可以介导 RA 中的炎症和关节破坏。人们逐渐认识到赖氨酸丙二酰化（Kmal）可以调节某些原核生物和真核生物中的一些生物学过程。然而，关于 Kmal 在 RA 中的作用知之甚少。因此，我们进行了蛋白质组和丙二酰组分析，以探索 36 例 RA 患者和 82 例健康对照者外周血单个核细胞的蛋白质组学特征。通过基于液相色谱-串联质谱（LC-MS/MS）的分析，共检测到 938 个差异表达蛋白（DEPs）和 42 个差异丙二酰化蛋白（DMPs），其中有 55 个 Kmal 位点。功能分析表明，在中性粒细胞胞外陷阱形成（NETosis）途径中鉴定出两个具有四个丙二酰化位点的 DEP 和一个具有丙二酰化位点的 DMP。总的来说，这项研究不仅首次描述了 RA 中丙二酰组的特征，还揭示了丙二酰化可能参与了 NETosis 途径。意义：这是首次通过 LC-MS/MS 方法报道揭示 RA 中 Kmal 的蛋白质组特征。在这项研究中，我们发现几个关键的 DMPs与 NETosis 途径有关，这有助于 RA 的发展。本研究结果为今后进一步探索 RA 中的 Kmal 提供了有价值的数据集。
