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Tocol Prophylaxis for Total-body Irradiation: A Proteomic Analysis in Murine Model.
Health Physics ( IF 1.0 ) Pub Date : 2020-3-25 , DOI: 10.1097/hp.0000000000001221
Elliot Rosen 1 , Oluseyi O Fatanmi , Stephen Y Wise , V Ashutosh Rao 1 , Vijay K Singh
Affiliation  

The aim of this study was to analyze the changes in mouse jejunum protein expression in response to prophylactic administration of two promising tocols, γ-tocotrienol (GT3) and α-tocopherol succinate (TS), as radiation countermeasures before irradiation to elucidate the molecular mechanism(s) of their radioprotective efficacy. Mice were administered GT3 or TS (200 mg kg) subcutaneously 24 h prior to exposure to 11 Gy Co γ-radiation, a supralethal dose for mice. Jejunum was harvested 24 h post-irradiation. Results of the two-dimensional differential in-gel electrophoresis (2D-DIGE), coupled with mass spectrometry, and advanced bioinformatics tools suggest that the tocols have a corresponding impact on expression of 13 proteins as identified by mass spectrometry. Ingenuity Pathway Analysis (IPA) reveals a network of associated proteins involved in inflammatory response, organismal injury and abnormalities, and cellular development. Relevant signaling pathways including actin cytoskeleton signaling, RhoA signaling, and Rho family GTPase were identified. This study reveals the major proteins, pathways, and networks involved in preventing the radiation-induced injury in gut that may be contributing to enhanced survival.

中文翻译:

全身照射的母育酚预防:小鼠模型中的蛋白质组学分析。

这项研究的目的是分析小鼠空肠蛋白质表达的变化,这是对两种有希望的母育酚γ-生育三烯酚(GT3)和α-生育酚琥珀酸酯(TS)的预防性给药的反应,作为辐射对策以阐明分子机制(s)的放射防护功效。在暴露于11 Gy Coγ射线(小鼠的超上剂量)之前24小时,皮下给予小鼠GT3或TS(200 mg kg)。照射后24小时收获空肠。二维差分凝胶电泳(2D-DIGE),质谱和先进的生物信息学工具的结果表明,母育酚对13种蛋白质的表达具有相应的影响,如质谱所鉴定。机能途径分析(IPA)揭示了与炎症反应,机体损伤和异常以及细胞发育有关的相关蛋白网络。确定了包括肌动蛋白细胞骨架信号传导,RhoA信号传导和Rho家族GTPase在内的相关信号传导途径。这项研究揭示了主要的蛋白质,途径和网络,它们与预防辐射引起的肠道损伤有关,这些损伤可能有助于提高生存率。
更新日期:2020-12-17
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