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Alterations of Brain Quantitative Proteomics Profiling Revealed the Molecular Mechanisms of Diosgenin against Cerebral Ischemia Reperfusion Effects.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-01-15 , DOI: 10.1021/acs.jproteome.9b00667
Xinxin Zhang 1, 2 , Xingbin Wang 1 , Muhammad Khurm 1 , Guanqun Zhan 1 , Hui Zhang 1 , Yoichiro Ito 3 , Zengjun Guo 1
Affiliation  

Diosgenin (DIO), the starting material for the synthesis of steroidal anti-inflammatory drugs in the pharmaceutical industry, has been previously demonstrated to display pharmaceutical effects against cerebral ischemic reperfusion (I/R). However, the alterations of brain proteome profiles underlying this treatment remain elusive. In the present study, the proteomics analysis of the brain tissues from I/R rats after DIO treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with the liquid chromatography with tandem mass spectrometry technology. A total of 5043 proteins (ProteomeXchange identifier: PXD016303) were identified, of which 58 common differentially expressed proteins were significantly dysregulated in comparison between sham versus I/R and I/R versus DIO. The eight validated proteins including EPG5, STAT2, CPT1A, EIF2AK2, GGCT, HIKESHI, TNFAIP8, and EMC6 by quantitative polymerase chain reaction and western blotting consistently supported the TMT-based proteomic results, which were mainly associated with autophagy and inflammation response. Considering the anti-inflammatory characters of DIO, the biological functions of STAT2 and HIKESHI that are the probable direct anti-inflammatory targets were further investigated during the course of I/R treated with DIO. In addition, the combination of verified STAT2 and HIKESHI in peripheral blood samples from stroke patients resulted in the area under the curve value of 0.765 with P < 0.004 to distinguish stroke patients from healthy controls. Taken together, the current findings first mapped comprehensive proteomic changes after I/R was treated with DIO to better decipher the molecular mechanisms mainly based on the anti-inflammatory aspect underlying this therapeutic effect, providing a foundation for developing potentially therapeutic targets of anti-I/R of DIO and clinically prognostic biomarkers of stroke.

中文翻译:

脑定量蛋白质组学分析的变化揭示了薯os皂苷元抗脑缺血再灌注作用的分子机制。

薯os皂素(DIO)是制药工业中合成类固醇消炎药的起始原料,先前已被证明具有抗脑缺血再灌注(I / R)的药物作用。然而,这种治疗基础的脑蛋白质组特征的改变仍然难以捉摸。在本研究中,DIO处理后I / R大鼠脑组织的蛋白质组学分析是使用基于TMT的集成定量蛋白质组学方法与液相色谱和串联质谱技术相结合进行的。总共鉴定了5043个蛋白(ProteomeXchange标识符:PXD016303),其中58个常见的差异表达蛋白在假装与I / R和I / R与DIO的比较中明显失调。八种经过验证的蛋白质,包括EPG5,STAT2,CPT1A,EIF2AK2,GGCT,HIKESHI,TNFAIP8和EMC6通过定量聚合酶链反应和Western blotting始终支持基于TMT的蛋白质组学结果,这主要与自噬和炎症反应有关。考虑到DIO的抗炎特性,在用DIO治疗I / R的过程中进一步研究了STAT2和HIKESHI的生物学功能,它们可能是直接的抗炎目标。此外,中风患者外周血样本中经过验证的STAT2和HIKESHI的组合导致曲线值在0.765下,P <0.004,从而将中风患者与健康对照区分开。在一起
更新日期:2020-02-06
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