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创伤后应激障碍大鼠模型易感性和抗应激的定量蛋白质组学分析。

Quantitative Proteomics Analysis of Susceptibility and Resilience to Stress in a Rat model of PTSD.

机构信息

Department of Anesthesiology, Guangdong Women and Children Hospital, Guangzhou, China.

Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, China.

出版信息

Behav Brain Res. 2021 Oct 11;415:113509. doi: 10.1016/j.bbr.2021.113509. Epub 2021 Aug 3.

Abstract

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder and sometimes deadly consequence of exposure to severe psychological trauma. However, there has been little known about the definitive molecular changes involved in determining vulnerability to PTSD. In the current study, we used proteomics to quantify protein changes in the hippocampus of foot shocks rats. A total of 6151 proteins were quantified and 97 proteins were significantly differentially expressed. The protein-protein interaction (PPI) analysis showed that oxidation-reduction process and glutathione homeostasis may be the potential key progress of being vulnerable to PTSD. The Gene Ontology analysis revealed enriched GO terms in the protein groups of Susceptible group vs Control group rats for glutathione binding,oligopeptide binding,modified amino acid binding,and glutathione transferase activity for their molecular functions (MF) and in the process of cellular response to toxic substance,xenobiotic metabolic process, urea metabolic process, and response to drug for the biological process (BP).SIGNIFICANCE:In recent years, there has been a growing interest in mental illness associated with trauma exposure. We found that stress susceptibility was associated with increased expression of arginase 1 indicated as a potential treatment target. Our results also proposed that carbonic anhydrases 3 could be a biomarker for the development of PTSD. This research helps to explain the potential molecular mechanism in PTSD and supply a new method for ameliorating PTSD.

摘要

创伤后应激障碍(PTSD)是一种普遍存在的精神障碍,也是暴露于严重心理创伤后的致命后果。然而,对于决定 PTSD 易感性的明确分子变化,人们知之甚少。在目前的研究中,我们使用蛋白质组学来定量分析足部电击大鼠海马体中的蛋白质变化。共定量了 6151 种蛋白质,其中 97 种蛋白质表达差异显著。蛋白质-蛋白质相互作用(PPI)分析表明,氧化还原过程和谷胱甘肽稳态可能是易患 PTSD 的潜在关键进展。基因本体论(GO)分析显示,在易感组和对照组大鼠的蛋白质组中,与谷胱甘肽结合、寡肽结合、修饰氨基酸结合和谷胱甘肽转移酶活性相关的 GO 术语在分子功能(MF)中富集,而在细胞对有毒物质的反应、异生物质代谢过程、尿素代谢过程和对药物的反应过程中富集在生物过程(BP)中。意义:近年来,人们对与创伤暴露相关的精神疾病越来越感兴趣。我们发现,应激易感性与精氨酸酶 1 的表达增加有关,这表明其可能是一个潜在的治疗靶点。我们的研究结果还表明,碳酸酐酶 3 可能是 PTSD 发展的生物标志物。这项研究有助于解释 PTSD 中的潜在分子机制,并为改善 PTSD 提供了一种新方法。

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