Research Article

内质网应激增加多药抗性蛋白2的表达并减轻急性肝损伤

卷 20, 期 7, 2020

页: [548 - 557] 页: 10

弟呕挨: 10.2174/1566524020666200124102411

价格: $65

摘要

背景:多药耐药蛋白(MRP)2是在肝细胞上表达并受核因子κB(NF-κB)调节的关键膜转运蛋白。有趣的是,内质网应激与肝损伤和NF-κB信号传导密切相关。 目的:在这里,我们研究了内质网应激对急性肝损伤中MRP2表达和MRP2功能参与的影响。 方法:在四氯化碳(CCl4)诱导的小鼠急性肝损伤模型和毒胡萝卜素(TG)诱导的ER应激模型中分析了ER应激,MRP2表达和肝细胞损伤。 结果:CCl4和TG诱导小鼠和LO2细胞显着的ER应激,MRP2蛋白表达和NF-κB活化(P <0.05)。 ER应激抑制剂4-苯基丁酸(PBA)预处理可显着减轻CCl4和TG诱导的ER应激和MRP2蛋白表达(P <0.05)。此外,用吡咯烷二硫代氨基甲酸(PDTC;NF-κB抑制剂)预处理可显着抑制CCl4诱导的NF-κB活化并降低MRP2蛋白表达(1} 0.097对0.623} 0.054; P <0.05)。此外,肝脏MRP2表达的下调显着增加了CCl4诱导的ER应激,细胞凋亡和肝损伤。 结论:内质网应激可通过激活NF-κB增强肝内MRP2蛋白的表达。 MRP2表达的增加减轻了内质网应激和急性肝损伤。

关键词: 多药耐药蛋白2,内质网应激,细胞凋亡,坏死病,核因子κB,急性肝损伤。

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