Prdx1 Reduces Intracerebral Hemorrhage-Induced Brain Injury via Targeting Inflammation- and Apoptosis-Related mRNA Stability.

Guo-Qiang Yang,Guo-Hui Jiang,Le-Xing Xie,Kai Zhou,Ru Chen,Qing-Wu Yang,Chang-Xiong Gong,Qi Xie,Xiao-Yi Xiong,Rui Xu,Zhong-Ming Qiu,Jun-Jie Yuan,Qiong Chen,Qin Zhang,Jia-Cheng Huang

doi:10.3389/fnins.2020.00181

Guo-Qiang Yang, Guo-Hui Jiang + Show 13 more

Open Access

https://doi.org/10.3389/fnins.2020.00181

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Abstract

RNA-binding proteins (RBPs) have been shown to be involved in posttranscriptional regulation, which plays an important role in the pathophysiology of intracerebral hemorrhage (ICH). Peroxiredoxin 1 (Prdx1), an RBP, plays an important role in regulating inflammation and apoptosis. On the basis that inflammation and apoptosis may contribute to ICH-induced brain injury, in this study, we used ICH models coupled with in vitro experiments, to investigate the role and mechanism of Prdx1 in regulating inflammation and apoptosis by acting as an RBP after ICH. We first found that Prdx1 was significantly up-regulated in response to ICH-induced brain injury and was mainly expressed in astrocytes and microglia in ICH rat brains. After overexpressing Prdx1 by injecting adeno-associated virus (AAV) into the striatum of rats at 3 weeks, we constructed ICH models and found that Prdx1 overexpression markedly reduced inflammation and apoptosis after ICH. Furthermore, RNA immunoprecipitation combined with high-throughput sequencing (RIP-seq) in vitro revealed that Prdx1 affects the stability of inflammation- and apoptosis-related mRNA, resulting in the inhibition of inflammation and apoptosis. Finally, overexpression of Prdx1 significantly alleviated the symptoms and mortality of rats subjected to ICH. Our results show that Prdx1 reduces ICH-induced brain injury by targeting inflammation- and apoptosis-related mRNA stability. Prdx1 may be an improved therapeutic target for alleviating the brain injury caused by ICH.

Highlights

Intracerebral hemorrhage (ICH) is a common type of stroke, with increasing incidence and mortality worldwide (Krishnamurthi et al, 2013)
We found that Peroxiredoxin 1 (Prdx1) protein levels (Figure 2C) in model rats were significantly increased compared to the level in the sham group at 3 days after intracerebral hemorrhage (ICH)
Immunofluorescence staining was used to explore the cellular resource of Prdx1 in normal brain tissue and perihematomal brain tissues in the striatum (Supplementary Figure S2B), and we found that Prdx1 was mainly colocalized with GFAP+ astrocytes and Iba1+ microglia (Figure 2E and Supplementary Figure S2A)

Summary

Introduction

Intracerebral hemorrhage (ICH) is a common type of stroke, with increasing incidence and mortality worldwide (Krishnamurthi et al, 2013). Increasing evidence shows that inflammation and apoptosis contribute to the brain injury seen in ICH, which is closely related to the severity of the patient’s symptoms and prognosis (Zheng et al, 2016). Improved therapeutic targets that could inhibit both inflammation and apoptosis need to be developed for the treatment of ICH. Accessing posttranscriptional regulation is important to influence the occurrence and development of diseases, such as ICH (Dykstra-Aiello et al, 2015, 2016; Stamova et al, 2019). Targeting posttranscriptional regulation via RBPs may alleviate the brain injury caused by ICH, as the progression of ICH has been shown to be closely regulated by posttranscriptional regulation (Dykstra-Aiello et al, 2015, 2016; Stamova et al, 2019)

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