Comprehensive analysis of lysine crotonylation in proteome of maintenance hemodialysis patients.
Comprehensive analysis of lysine crotonylation in proteome of maintenance hemodialysis patients.
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DOI：
10.1097/md.0000000000012035
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发表时间：
2018-09
期刊：
影响因子：
1.6
通讯作者：
Diao H
中科院分区：
文献类型：
--
作者：
Chen W;Tang D;Xu Y;Zou Y;Sui W;Dai Y;Diao H
组蛋白翻译后修饰（PTM）携带表观遗传信息，在染色质水平上调节各种细胞过程。巴豆酰化是最重要和最常见的蛋白质翻译后修饰之一，在多种生物学过程的调控中起着关键作用。然而，没有研究评估赖氨酸巴豆酰化在维持性血液透析患者（MHP）中的作用。在这里，我们比较评估的巴豆酰化蛋白质组的正常对照（NC）和MHP使用液相色谱串联质谱（LC-MS/MS）加上高灵敏度的免疫亲和纯化。共有1109个赖氨酸修饰位点分布在347个蛋白质上，分别包括93个和252个巴豆酰化上调和下调的蛋白质。因此，在接受维持性血液透析的肾衰竭患者中观察到组蛋白的巴豆酰化减少。深入的生物信息学分析表明，大多数巴豆酰化蛋白分布在细胞质、细胞核、线粒体和细胞外区域。基因本体富集分析表明，巴豆酰化蛋白质显着富集在血小板α颗粒腔，血小板脱粒，细胞粘附分子结合。此外，蛋白质结构域，包括纤维蛋白原α/β/γ链，锌指，和WD 40-重复的结构域，显着丰富的巴豆酰化蛋白。基于京都基因和基因组百科全书（KEGG）的功能富集分析显示，巴豆酰化蛋白在补体和凝血级联、心肌收缩和造血细胞谱系中富集，所有这些都与血液透析并发症有重要关联。这是首次报道的全球巴豆酰化蛋白质组的MHP。赖氨酸巴豆酰化在MHP的病理生理过程中起着重要的调节作用。
Supplemental Digital Content is available in the text Histone post-translational modifications (PTMs) carry epigenetic information to regulate diverse cellular processes at the chromatin level. Crotonylation, one of the most important and common PTMs, plays a key role in the regulation of various biological processes. However, no study has evaluated the role of lysine crotonylation in maintenance hemodialysis patients (MHP). Here, we comparatively evaluated the crotonylation proteome of normal controls (NC) and MHP using liquid chromatography tandem mass spectrometry (LC-MS/MS) coupled with highly sensitive immune-affinity purification. A total of 1109 lysine modification sites distributed on 347 proteins were identified, including 93 and 252 crotonylated upregulated and downregulated proteins, respectively. Thus, a decrease in crotonylation of histone proteins was observed in patients with kidney failure undergoing maintenance hemodialysis. Intensive bioinformatic analysis revealed that most of the crotonylated proteins were distributed in the cytoplasm, nucleus, mitochondria, and extracellular region. Gene ontology enrichment analysis showed that the crotonylated proteins were significantly enriched in the platelet alpha granule lumen, platelet degranulation, and cell adhesion molecule binding. In addition, protein domain, including fibrinogen alpha/beta/gamma chain, zinc finger, and WD40-repeat-containing domain, were significantly enriched in crotonylated proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment analysis revealed that crotonylated proteins were enriched in complement and coagulation cascades, cardiac muscle contraction, and hematopoietic cell lineage, all of which have important associations with hemodialysis complications. This is the first report on the global crotonylation proteome of MHP. Lysine crotonylation was found to play important regulatory roles in pathophysiological processes in MHP.