The proteomic study and the target discovery of W026B, a new compound with brain protective effect

doi:10.5246/jcps.2019.06.037

Abstract

Abstract:

W026B is a new compound that has a protective effect on cerebral ischemia reperfusion (I-R) injury in mice, while its specific mechanism is still unknown. In this study, proteomics was used to observe the effect of W026B on protein expression in brain I-R tissue, and to reveal its potential target. A total of 42 significantly altered proteins were identified in both brain I-R model and W026B treatment from 4852 proteins detected by proteomics, and most of these proteins were related to immunity and inflammation, metabolism, neuroprotection as well as cell proliferation and cell structure. Western blotting analysis showed that three out of five selected proteins showed consistent alteration with the proteomics. Regulator of G protein signaling 17 (RGS17) was selected for further study, and its knockdown by siRNA RGS17 aggravated brain injury and abolished the protective effect of W026B. W026B could bind with RGS17 (K_D: 6.04×10^–⁶ mol/L). The knockdown of RGS17 aggravated Neuro-2a cell damage induced by group I metabotropic glutamate receptors (mGluRs) agonist, and abolished the protective effect of W026B. In conclusion, W026B protected brain against I-R injury by affecting diverse proteins. RGS17 might be one of its targets and a potential therapeutic target of brain I-R injury. The upstream receptor of G protein, which was regulated by RGS17 and affected by W026B, might be group I mGluRs. This study provided useful evidence for the further R&D and the potential clinical application of W026B.

Key words: Brain ischemia, Reperfusion injury, Proteomics, Target discovery, W026B

CLC Number:

R965

Supporting:

Siyu Zhao, Xiaoyan Liu, Yuanjun Zhu, Ye Liu, Yinye Wang. The proteomic study and the target discovery of W026B, a new compound with brain protective effect[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(6): 381-392.

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