Peroxiredoxin 1/2 protects brain against H2O2-induced apoptosis after subarachnoid hemorrhage
Peroxiredoxin 1/2 protects brain against H2O2-induced apoptosis after subarachnoid hemorrhage
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Peroxiredoxin 1/2 保护大脑免受蛛网膜下腔出血后 H2O2 诱导的细胞凋亡
DOI：
10.1096/fj.201801150r
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发表时间：
2019-02-01
期刊：
影响因子：
4.8
通讯作者：
Hang, Chun-Hua
中科院分区：
文献类型：
--
作者：
Lu, Yue;Zhang, Xiang-Sheng;Hang, Chun-Hua
最近的研究表明，过氧化还蛋白1/2(Prooxiredoxin1/2，PRX1/2)可能参与了脑缺血后炎症反应的病理生理过程。在这项研究中，我们评估了PRX1/2在实验性蛛网膜下腔出血(SAH)小鼠体内的分布和功能。我们用免疫荧光染色的方法研究了PRX1/2在体内和体外小鼠脑内的分布。免疫印迹法检测蛛网膜下腔出血后PRX1/2的表达。用腺苷抑制PRX1/2功能，并通过注射腺相关病毒实现PRX1/2的高表达。在体内和体外评估氧化应激和神经细胞凋亡。分析神经功能、炎症反应及相关细胞信号。结果表明，Prx1主要在星形胶质细胞中表达，Prx2在神经元中大量表达。蛛网膜下腔出血后PRX1/2表达增强，其表达水平先于促炎细胞因子达到峰值。抑制PRX1/2通过增加细胞内过氧化氢(H_2O_2)水平，通过细胞凋亡信号调节激酶1/p38途径促进神经细胞的凋亡。相反，PRX1/2的过表达减轻了SAH后的氧化应激和神经细胞凋亡。因此，PRX1/2的早期表达可能保护SAH后的脑组织免受氧化损伤，并可能为治疗SAH提供一个新的靶点。
Recent studies suggest that peroxiredoxin1/2 (Prx1/2) may be involved in the pathophysiology of postischemic inflammatory responses in the brain. In this study, we assessed the distribution and function of Prx1/2 in mice after experimental subarachnoid hemorrhage (SAH). We investigated the distribution of Prx1/2 in the brains of mice both in vivo and in vitro using immunofluorescence staining. The expression of Prx1/2 after SAH was determined by Western blot. Adenanthin was used to inhibit Prx1/2 function, and Prx1/2 overexpression was achieved by injecting adeno-associated virus. Oxidative stress and neuronal apoptosis were assessed both in vivo and in vitro. The neurologic function, inflammatory response, and related cellular signals were analyzed. The results showed that Prx1 was mainly expressed in astrocytes, and Prx2 was abundant in neurons. The expression of Prx1/2 was elevated after SAH, and their expression levels peaked before proinflammatory cytokines. Inhibiting Prx1/2 promoted neuronal apoptosis by increasing the hydrogen peroxide (H2O2) levels via the apoptosis signal-regulating kinase 1/p38 pathway. By contrast, overexpression of Prx1/2 attenuated oxidative stress and neuronal apoptosis after SAH. Thus, early expression of Prx1/2 may protect the brain from oxidative damage after SAH and may provide a novel target for treating SAH.Lu, Y., Zhang, X.-S., Zhou, X.-M., Gao, Y.-Y., Chen, C.-L., Liu, J.-P., Ye, Z.-N., Zhang, Z.-H., Wu, L.-Y., Li, W., Hang, C.-H. Peroxiredoxin 1/2 protects brain against H2O2-induced apoptosis after subarachnoid hemorrhage.