GABARAPL1 和 2 相关神经元中七氟醚双重作用的自噬网络分析。
Autophagic Network Analysis of the Dual Effect of Sevoflurane on Neurons Associated with GABARAPL1 and 2.
机构信息
Department of Anesthesiology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001 Fujian Province, China.
Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001 Fujian Province, China.
出版信息
Biomed Res Int. 2020 Jun 26;2020:1587214. doi: 10.1155/2020/1587214. eCollection 2020.
BACKGROUND
Sevoflurane is commonly used as a general anesthetic in neonates to aged patients. Preconditioning or postconditioning with sevoflurane protects neurons from excitotoxic injury. Conversely, sevoflurane exposure induces neurotoxicity during early or late life. However, little is known about the underlying mechanism of the dual effect of sevoflurane on neurons. Autophagy is believed to control neuronal homeostasis. We hypothesized that autophagy determined the dual effect of sevoflurane on neurons.
METHODS
DTome was used to identify the direct protein target (DPT) of sevoflurane. The STRING database was employed to investigate the proteins associated with the DPTs. Protein-protein interaction was assessed using Cytoscape. WebGestalt was used to analyze gene set enrichment. The linkage between candidate genes and autophagy was identified using GeneCards.
RESULTS
This study found that 23 essential DPTs of sevoflurane interacted with 77 proteins from the STRING database. GABARAPL1 and 2, both of which are DPT- and autophagy-associated proteins, were significantly expressed in the brain and enriched in GABAergic synapses.
CONCLUSIONS
Taken together, our findings showed that the network of sevoflurane-DPT-GABARAPL1 and 2 is related to the dual effect of sevoflurane on neurons.
背景
七氟醚常用于新生儿至老年患者的全身麻醉。七氟醚预处理或后处理可保护神经元免受兴奋性损伤。相反，七氟醚暴露在生命早期或晚期会诱导神经毒性。然而，关于七氟醚对神经元的双重作用的潜在机制知之甚少。自噬被认为可以控制神经元的内稳态。我们假设自噬决定了七氟醚对神经元的双重作用。
方法
DTome 用于鉴定七氟醚的直接蛋白靶标 (DPT)。STRING 数据库用于研究与 DPTs 相关的蛋白质。使用 Cytoscape 评估蛋白质-蛋白质相互作用。WebGestalt 用于分析基因集富集。使用 GeneCards 确定候选基因与自噬之间的联系。
结果
本研究发现，23 种七氟醚的必需 DPT 与 STRING 数据库中的 77 种蛋白质相互作用。GABARAPL1 和 2 均为 DPT 和自噬相关蛋白，在大脑中表达明显，并富集在 GABA 能突触中。
结论
综上所述，我们的研究结果表明，七氟醚-DPT-GABARAPL1 和 2 的网络与七氟醚对神经元的双重作用有关。
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