The role of PSMB5 in sodium arsenite-induced oxidative stress in L-02 cells
The role of PSMB5 in sodium arsenite-induced oxidative stress in L-02 cells
复制标题
PSMB5 在亚砷酸钠诱导的 L-02 细胞氧化应激中的作用
DOI：
10.1007/s12192-020-01104-1
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发表时间：
2020-05-01
影响因子：
3.8
通讯作者：
Hu, Yong
中科院分区：
文献类型：
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作者：
Lv, Ying;Hu, Qian;Hu, Yong
地方性砷中毒在世界范围内分布广泛，可损害多个器官，尤其是皮肤和肝脏。病因很清楚，但涉及的机制尚不清楚。泛素-蛋白酶体途径(UPP)是调节蛋白质降解的主要途径，其中蛋白酶体β5亚单位(PSMB5)起主导作用。本论文旨在研究PSMB5在亚砷酸钠(NaAsO2)诱导的L-02细胞氧化应激性肝损伤中的作用及其机制。首先，将L-02细胞暴露于不同浓度的NaAsO2中，建立氧化应激肝损伤模型，然后用苯甲氧基亮氨酰-亮氨酸羧基转移酶(MG132)和基因敲除的PSMB5(PSMB5-siRNA)研究氧化应激的机制。检测氧化应激指标、20S蛋白酶体水平、PSMB5、铜锌超氧化物歧化酶(SOD1)和谷胱甘肽过氧化物酶1(GPX1)的转录和蛋白表达水平。结果表明，NaAsO2可诱导氧化应激性肝损伤，20S蛋白酶体活性降低，PSMB5、SOD1、GPX1蛋白表达降低。经MG132或PSMB5-siRNA处理后，PSMB基因表达下降。经MG132或PSMB5-siRNA处理后，再用NaAsO2处理L-02细胞后，PSMB的基因表达显著降低，而SOD1和GPX1的蛋白表达增加。总之，NaAsO2暴露可导致L-02细胞氧化应激性肝损伤和PSMB5的低表达，PSMB5可能通过调节SOD1和GPX1的表达在氧化应激的调节中发挥重要作用。
Endemic arsenism is widely distributed in the world, which can damage multiple organs, especially in skin and liver. The etiology is clear, but the mechanisms involved remain unknown. Ubiquitin-proteasome pathway (UPP) is the main pathway regulating protein degradation of which proteasome subunit beta type-5(PSMB5) plays a dominant role. This paper aims to study the role and mechanism of PSMB5 in sodium arsenite (NaAsO2)–induced oxidative stress liver injury in L-02 cells. Firstly, L-02 cells were exposed to different concentrations of NaAsO2to establish a liver injury model of oxidative stress, and then mechanisms of oxidative stress were studied with carbobenzoxyl-leucyl-leucl-leucll-line (MG132) and knockdown PSMB5 (PSMB5-siRNA). The oxidative stress indicators, levels of 20S proteasome, the transcription and protein expression levels of PSMB5, Cu-Zn superoxide dismutase (SOD1), and glutathione peroxidase 1 (GPx1) were detected. The results demonstrated that NaAsO2could induce oxidative stress–induced liver injury and the activity of 20S proteasome and the protein expression of PSMB5, SOD1, and GPx1 decreased. After MG132 or PSMB5-siRNA pretreatment, the gene expression of PSMB decreased. After MG132 or PSMB5-siRNA pretreatment, and then L-02 cells were treated with NaAsO2, the gene expression of PSMB remarkably decreased; however, the protein expression of SOD1 and GPx1 increased. Overall, NaAsO2exposure could induce oxidative stress liver injury and low expression of PSMB5 in L-02 cells, and PSMB5 might play an important role in the regulation of oxidative stress by regulating the expression of SOD1 and Gpx1.