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脑出血后,Nrdp1通过下调Bruce增加神经元凋亡。

Nrdp1 increases neuron apoptosis via downregulation of Bruce following intracerebral haemorrhage.

作者信息

Zhou Changlong, Liu Qingjun, Zhao Wang, Yang Ling, Huang Zhongyan, Yang Zhao

机构信息

1Department of Neurosurgery, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160 China.

2Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160 China.

出版信息

J Inflamm (Lond). 2019 Dec 9;16:24. doi: 10.1186/s12950-019-0229-8. eCollection 2019.

Abstract

BACKGROUND

Neuregulin receptor degradation protein-1 (Nrdp1) is an E3 ubiquitin ligase that plays an important role in regulating cell growth, apoptosis and oxidative stress. However, the data regarding its expression and exact mechanism in neuronal injury following ICH has not been well identified.

METHODS

In this study, primary cortical neurons from C57BL/6 mice were subjected to erythrocyte lysates. Nrdp1 expression, cell apoptosis, caspase-3 and BRUCE levels were detected. In addition, inflammatory response, brain edema, and neurological injury in ICH mice were also assessed.

RESULTS

We found that the expression of Nrdp1 was significantly increased in neuron cells accompanied by up-regulation of active caspase-3 and decreased expression of BRUCE (an inhibitor of apoptosis protein). However, inhibiting Nrdp1 levels of neurons reduced caspase-3 activity but induced up-regulation of BRUCE. In vivo, inhibiting Nrdp1 levels increased pro-inflammatory cytokines, brain edema, and neurological injury following ICH.

CONCLUSIONS

Taken together, the data suggested that Nrdp1 might play a crucial role in neuronal apoptosis via inhibiting BRUCE following ICH.

摘要

背景

神经调节蛋白受体降解蛋白1(Nrdp1)是一种E3泛素连接酶,在调节细胞生长、凋亡和氧化应激中起重要作用。然而,关于其在脑出血后神经元损伤中的表达及确切机制的数据尚未得到充分证实。

方法

在本研究中,将来自C57BL/6小鼠的原代皮质神经元用红细胞裂解物处理。检测Nrdp1表达、细胞凋亡、半胱天冬酶-3和BRUCE水平。此外,还评估了脑出血小鼠的炎症反应、脑水肿和神经损伤。

结果

我们发现,神经元细胞中Nrdp1的表达显著增加,同时活性半胱天冬酶-3上调,凋亡抑制蛋白BRUCE的表达降低。然而,抑制神经元的Nrdp1水平可降低半胱天冬酶-3活性,但诱导BRUCE上调。在体内,抑制Nrdp1水平会增加脑出血后的促炎细胞因子、脑水肿和神经损伤。

结论

综上所述,数据表明Nrdp1可能在脑出血后通过抑制BRUCE在神经元凋亡中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d70/6902554/68e02c85ce23/12950_2019_229_Fig1_HTML.jpg

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