Journal
FRONTIERS IN NEUROSCIENCE
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2020.00181
Keywords
RNA-binding protein; peroxiredoxin 1; intracerebral hemorrhage; inflammation; apoptosis; posttranscriptional regulation
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Funding
- 13th Five-Year National Key RD Program [2016YFC1300505]
- National Natural Science Fund for Distinguished Young Scholars [81525008]
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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.
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