当前位置: X-MOL 学术Cell. Mol. Neurobiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Deep Succinylproteomics of Brain Tissues from Intracerebral Hemorrhage with Inhibition of Toll-Like Receptor 4 Signaling
Cellular and Molecular Neurobiology ( IF 3.6 ) Pub Date : 2021-08-30 , DOI: 10.1007/s10571-021-01144-w
Yan-Jing Liang 1 , Yuan-Rui Yang 2 , Chuan-Yuan Tao 3 , Su-Hao Yang 1 , Xin-Xiao Zhang 1 , Jing Yuan 1 , Yuan-Hong Deng 1 , Zhan-Qiong Zhong 4 , Shu-Guang Yu 1, 5 , Xiao-Yi Xiong 1, 5
Affiliation  

It is unclear how Toll-like receptor (TLR) 4 signaling affects protein succinylation in the brain after intracerebral hemorrhage (ICH). Here, we constructed a mouse ICH model to investigate the changes in ICH-associated brain protein succinylation, following a treatment with a TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized the prevalence of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase of 29 succinyllysine sites on 28 succinylated proteins and a reduction of 24 succinyllysine sites on 23 succinylated proteins in the ICH brains. TAK242 treatment induced both protein hypersuccinylations and hyposuccinylations, which were mainly located in the mitochondria and cytoplasm. GO analysis showed that TAK242 treatment-induced changes in the ICH-associated succinylated proteins were mostly located in synapses, membranes and vesicles, and enriched in many cellular functions/compartments, such as metabolism, synapse, and myelin. KEGG analysis showed that TAK242-induced hyposuccinylation was mainly linked to fatty acid metabolism, including elongation and degradation. Moreover, a combined analysis of the succinylproteomic data with previously published transcriptome data revealed that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed throughout neurons, astrocytes, and endothelial cells, and the mRNAs of seven and three succinylated proteins were highly expressed in neurons and astrocytes, respectively. In conclusion, we revealed that several TLR4 signaling pathways affect the succinylation processes and pathways in mouse ICH brains, providing new insights on the ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.



中文翻译:

抑制 Toll 样受体 4 信号传导的脑出血脑组织深层琥珀酰蛋白质组学

目前尚不清楚 Toll 样受体 (TLR) 4 信号如何影响脑出血 (ICH) 后大脑中的蛋白质琥珀酰化。在这里,我们构建了一个小鼠 ICH 模型,以研究 ICH 相关脑蛋白琥珀酰化的变化,在 TLR4 拮抗剂 TAK242 治疗后,使用基于高分辨率质谱的定量琥珀酰赖氨酸蛋白质组学方法。我们描述了大约 6700 次琥珀酰化事件的发生率并量化了大约 3500 个位点,突出了 40 个途径中的 139 个琥珀酰赖氨酸位点变化。进一步的分析表明,TAK242 处理诱导 ICH 大脑中 28 个琥珀酰化蛋白质上的 29 个琥珀酰赖氨酸位点增加和 23 个琥珀酰化蛋白质上的 24 个琥珀酰赖氨酸位点减少。TAK242 处理诱导了主要位于线粒体和细胞质中的蛋白质高琥珀酰化和低琥珀酰化。GO 分析表明,TAK242 治疗诱导的 ICH 相关琥珀酰化蛋白的变化主要位于突触、膜和囊泡中,并富含许多细胞功能/隔室,例如代谢、突触和髓磷脂。KEGG分析表明,TAK242诱导的次琥珀酰化主要与脂肪酸代谢有关,包括延伸和降解。此外,对琥珀酰蛋白质组学数据与先前发表的转录组数据的综合分析表明,TAK242 处理诱导的大多数差异琥珀酰化蛋白主要分布在神经元、星形胶质细胞和内皮细胞中,7 种和 3 种琥珀酰化蛋白的 mRNA 分别在神经元和星形胶质细胞中高表达。总之,我们揭示了几种 TLR4 信号通路影响小鼠 ICH 大脑中的琥珀酰化过程和通路,为 ICH 的病理生理过程提供了新的见解。数据可通过 ProteomeXchange 获得,标识符为 PXD025622。

更新日期:2021-08-31
down
wechat
bug