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Silencing of TXNIP Alleviated Oxidative Stress Injury by Regulating MAPK–Nrf2 Axis in Ischemic Stroke

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Abstract

Ischemic stroke is a life-threatening cerebrovascular thrombotic disease, oxidative stress is considered to be a critical factor to stroke pathophysiology. This study aimed to investigate the underlying molecular mechanism and propose the potential therapeutic strategy for ischemic stroke. Bioinformatics analysis based on a public microarray profile (GSE 61616) of ischemic stroke rats was performed as a pilot research. Oxidative stress was enriched as a significantly gene ontology item, and thioredoxin-interacting protein (TXNIP) and MAPK signaling were identified as the hub gene and pathway, respectively. The experiments in middle cerebral artery occlusion rats demonstrated that ischemia induced the activation of oxidative stress. The expressions of TXNIP, p-p38, p-JNK, p-ERK were significantly increased while Nrf2 and HO-1 expressions were decreased after stroke. Rescue assays were conducted in primary cultured neurons to explore the accurate interrelations among these factors. The results indicated that MAPK specific inhibitor and siRNA-TXNIP significantly alleviated the oxidative stress injury induced by oxygen–glucose deprivation. In addition, knocking down of TXNIP inhibited the activation of MAPK pathway and promoted Nrf2 pathway. Taken together, these findings indicated that TXNIP aggravated the oxidative stress injury by regulating MAPK–Nrf2 axis in ischemic stroke. Silencing of TXNIP seems a promising therapeutic strategy to alleviate ischemic stroke.

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Acknowledgements

This research was funded by Heilongjiang Postdoctoral Science Foundation, Grant No. LBH-Z18175.

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Authors and Affiliations

  1. Department of Neurosurgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150086, China

    Yu Tian, Qile Ye, Lei Chen, Fei Yuan & Zhenyu Wang

  2. Functional Experimental Teaching Center, College of Basic Medical Sciences, Harbin Medical University, Harbin, 150086, China

    Yue Su

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  1. Yu Tian
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  2. Yue Su
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  3. Qile Ye
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Correspondence to Zhenyu Wang.

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Table S1

The 2750 differentially expressed genes (CSV 285 kb)

Table S2

The 880 significant GO items (CSV 74 kb)

Table S3

The genes involved in the co-expression network (CSV 9 kb)

Table S4

The pathways involved in the pathway relation network (CSV 3 kb)

Figure S1

The MAP2 staining for neurons (TIFF 1564 kb)

Figure S2

The CBF (cerebral blood flow) in right cerebral hemisphere before and after stroke (TIFF 47 kb)

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Tian, Y., Su, Y., Ye, Q. et al. Silencing of TXNIP Alleviated Oxidative Stress Injury by Regulating MAPK–Nrf2 Axis in Ischemic Stroke. Neurochem Res 45, 428–436 (2020). https://doi.org/10.1007/s11064-019-02933-y

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  • DOI: https://doi.org/10.1007/s11064-019-02933-y

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