Luo Weiguang, He Mei, Luo Qizhi, Li Yi
Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Henan Medical Key Laboratory of Arrhythmia, The 7th People's Hospital of Zhengzhou, Zhengzhou Cardiovascular Hospital, Zhengzhou, China.
Front Cardiovasc Med. 2023 Jan 9;9:1066822. doi: 10.3389/fcvm.2022.1066822. eCollection 2022.
Lysine ß-hydroxybutyrylation (kbhb), a novel modification of lysine residues with the ß-hydroxybuty group, is associated with ketone metabolism in numerous species. However, its potential role in diabetes, especially in diabetic cardiomyopathy (DCM), remains largely unexplored. In this study, using affinity enrichment and liquid chromatography-mass spectrometry (LC-MS/MS) method, we quantitatively analyze the kbhb residues on heart tissues of a DCM model rat. A total of 3,520 kbhb sites in 1,089 proteins were identified in this study. Further analysis showed that 336 kbhb sites in 143 proteins were differentially expressed between the heart tissues of DCM and wild-type rats. Among them, 284 kbhb sites in 96 proteins were upregulated, while 52 kbhb sites in 47 proteins were downregulated. Bioinformatic analysis of the proteomic results revealed that these kbhb-modified proteins were widely distributed in various components and involved in a wide range of cellular functions and biological processes (BPs). Functional analysis showed that the kbhb-modified proteins were involved in the tricarboxylic acid cycle, oxidative phosphorylation, and propanoate metabolism. Our findings demonstrated how kbhb is related to many metabolic pathways and is mainly involved in energy metabolism. These results provide the first global investigation of the kbhb profile in DCM progression and can be an essential resource to explore DCM's pathogenesis further.
赖氨酸β-羟基丁酰化（kbhb）是一种赖氨酸残基被β-羟基丁酰基团修饰的新型修饰方式，与众多物种的酮代谢相关。然而，其在糖尿病尤其是糖尿病性心肌病（DCM）中的潜在作用仍 largely unexplored。在本研究中，我们使用亲和富集和液相色谱-质谱联用（LC-MS/MS）方法，对DCM模型大鼠心脏组织中的kbhb残基进行了定量分析。本研究共鉴定出1089种蛋白质中的3520个kbhb位点。进一步分析表明，DCM大鼠和野生型大鼠心脏组织中，143种蛋白质上的336个kbhb位点存在差异表达。其中，96种蛋白质上的284个kbhb位点上调，47种蛋白质上的52个kbhb位点下调。对蛋白质组学结果的生物信息学分析表明，这些被kbhb修饰的蛋白质广泛分布于各种组分中，并参与多种细胞功能和生物学过程（BPs）。功能分析表明，被kbhb修饰的蛋白质参与三羧酸循环、氧化磷酸化和丙酸代谢。我们的研究结果表明了kbhb与许多代谢途径的关系，并且主要参与能量代谢。这些结果首次对DCM进展过程中的kbhb谱进行了全面研究，可为进一步探索DCM的发病机制提供重要资源。
