Proteomic profiling of sclerotic hippocampus revealed dysregulated packaging of vesicular neurotransmitters in temporal lobe epilepsy
Proteomic profiling of sclerotic hippocampus revealed dysregulated packaging of vesicular neurotransmitters in temporal lobe epilepsy
复制标题
硬化海马的蛋白质组学分析揭示了颞叶癫痫中囊泡神经递质的包装失调
DOI：
10.1016/j.eplepsyres.2020.106412
复制
发表时间：
2020-10-01
影响因子：
2.2
通讯作者：
Ge, Wei
中科院分区：
文献类型：
--
作者：
Zhang, Yusheng;Liu, Yifan;Ge, Wei
目的：颞叶癫痫（Temporal lobe epilepsy，TLE）是癫痫最常见的类型.海马硬化是TLE最显著的病理特征，但其在TLE发病机制中的作用尚不明确。方法：对4例TLE患者和4例正常对照海马组织进行蛋白质组学和生物信息学分析。高分辨率液相色谱-串联质谱法（LC-MS/MS）结合TMT-6plex定量，用于全局蛋白质表达分析。结果：经生物信息学分析，在突触囊泡通路、前列腺素合成和调节通路、内源性大麻素和突触传递通路的逆行调节中发现差异表达蛋白。其中，兴奋性氨基酸转运蛋白1（EAAT 1）和囊泡谷氨酸转运蛋白1（VGLUT 1）在TLE发病中起重要作用，其表达异常可能与细胞外谷氨酸的摄取密切相关，并参与TLE的病理生理过程。Ras相关蛋白Rab-3A（RAB 3A）的下调可能提示TLE引起的谷氨酸释放代偿性不足。结论：TLE引起囊泡神经递质包装相关蛋白的表达改变。此外，上调表达的膜联蛋白家族蛋白，这也与TLE，可能发挥重要作用，防止TLE。
Purpose: Temporal lobe epilepsy (TLE) is the most common type of epilepsy. Hippocampal sclerosis is the most distinctive pathological feature of TLE; however, its role in the pathogenesis of TLE remains to be clarified. We performed global protein expression analysis of hippocampus from TLE patients and controls, aiming to reveal the molecular signaling pathways related to TLE.Method: Proteomic and bioinformatic analyses of the hippocampus were performed on 4 TLE and 4 control samples. High-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with TMT-6plex quantification, was applied for global protein expression analysis. The proteomics results were validated by Western blot with 25 TLE and 25 control individuals and Immunohistochemistry analysis with 33 TLE and 10 control individuals.Results: Bioinformatics analysis demonstrated differentially expressed proteins in the synaptic vesicle pathway, the prostaglandin synthesis and regulation pathway and endocannabinoids and retrograde modulation of synaptic transmission pathway. Among these, excitatory amino acid transporter 1 (EAAT1) and Vesicular glutamate transporter 1 (VGLUT1) are critical for TLE and dysregulated expression might be closely related to the uptake of extracellular glutamate and contribute to the pathophysiology of TLE. Ras-related protein Rab-3A (RAB3A) downregulation might indicate the TLE-induced compensatory deficit in glutamate release.Conclusion: Our study indicates that expression of some proteins involved in the packaging of vesicular neurotransmitters is altered in TLE. In addition, upregulated expression of annexin family proteins, which are also related to TLE, might play an important role in protection against TLE.