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Alterations of Brain Quantitative Proteomics Profiling Revealed the Molecular Mechanisms of Diosgenin against Cerebral Ischemia Reperfusion Effects.

Abstract：

: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.

journal_name

J Proteome Res

journal_title

Journal of proteome research

authors

Zhang X,Wang X,Khurm M,Zhan G,Zhang H,Ito Y,Guo Z

doi

10.1021/acs.jproteome.9b00667

subject

Has Abstract

pub_date

2020-03-06 00:00:00

pages

1154-1168

issue

eissn

1535-3893

issn

1535-3907

journal_volume

pub_type

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Alterations of Brain Quantitative Proteomics Profiling Revealed the Molecular Mechanisms of Diosgenin against Cerebral Ischemia Reperfusion Effects.