氧化应激
内质网
硫氧还蛋白还原酶
硫氧还蛋白
未折叠蛋白反应
活性氧
细胞生物学
化学
脂质过氧化
药理学
生物
生物化学
作者
Xuanbei Liu,Enhui Hong,Jiayu Xie,Jiangwei Li,Boyun Ding,Yongsheng Chen,Zhennan Xia,Weiping Jiang,Hongzhu Lv,Bo Yang,Yizhao Chen
出处
期刊:Neuroscience
[Elsevier]
日期:2024-05-01
卷期号:545: 158-170
标识
DOI:10.1016/j.neuroscience.2024.03.019
摘要
Abstract
Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression. Primarily, expression and localization of Txnrd2, Trx2 and Prx3 were determined in collagenase IV-induced ICH model. Txnrd2 was then knocked down using siRNA interference in rats which were found to develop more severe encephaledema and neurological deficits. Mechanistically, we observed that loss of Txnrd2 leads to increased lipid peroxidation levels and ER stress protein expression in neurons and astrocytes. Additionally, it was revealed that Se effectively restored the expression of Txnrd2 in brain and inhibited both the activity of ER stress protein activity and the generation of reactive oxygen species (ROS) by promoting Trx2/Prx3 kilter when administrating sodium selenite in lateral ventricle. This study shed light on the effect of Txnrd2 in regulating oxidative stress and ER stress via Trx2/Prx3 pathway upon ICH and its promising potential as an ICH therapeutic target.
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