Salidroside alleviated hypoxia-induced liver injury by inhibiting endoplasmic reticulum stress-mediated apoptosis via IRE1α/JNK pathway
Salidroside alleviated hypoxia-induced liver injury by inhibiting endoplasmic reticulum stress-mediated apoptosis via IRE1α/JNK pathway
复制标题
红景天苷通过 IRE1α/JNK 通路抑制内质网应激介导的细胞凋亡，减轻缺氧引起的肝损伤
DOI：
10.1016/j.bbrc.2020.06.036
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发表时间：
2020-08-20
影响因子：
3.1
通讯作者：
Teng, Lianghong
中科院分区：
文献类型：
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作者：
Xiong, Yanlei;Wang, Yueming;Teng, Lianghong
内质网应激和随后的细胞凋亡在肝损伤和功能障碍中起重要作用。本研究旨在探讨红景天苷对缺氧性肝损伤的保护作用及其机制。雄性SD大鼠置于低压舱内模拟高原缺氧模型。高原缺氧可导致大鼠肝脏明显损伤和细胞凋亡，p-JNK、BAX和ER应激标志物表达水平升高。红景天苷处理通过降低葡萄糖调节蛋白78（GRP 78）、CCAAT/增强子结合蛋白同源蛋白（CHOP）和磷酸化肌醇需要酶1 α（p-IRE 1 α）的蛋白表达，显著抑制缺氧诱导的内质网应激。此外，红景天苷处理还抑制ER应激介导的凋亡途径，如通过降低促凋亡蛋白p-JNK、TRAF 2、BAX和裂解的半胱天冬酶9和半胱天冬酶12以及上调Bcl-2所示。此外，体外研究发现，使用特异性抑制剂STF-083010阻断IRE 1 α通路随后逆转了红景天苷对肝细胞凋亡的保护作用。综上所述，我们的研究结果表明红景天苷通过抑制ER应激介导的细胞凋亡，通过IRE 1 α/JNK途径对缺氧诱导的肝损伤发挥保护作用。(C)2020爱思唯尔公司All rights reserved.
Endoplasmic reticulum (ER) stress and subsequent apoptosis played vital role in liver injury and dysfunction. The aim of this study was to investigate the protective effect and mechanism of salidroside on hypoxia induced liver injury both in vivo and in vitro. Male SD rats were exposed to hypobaric chamber to simulate high altitude hypoxia model. High altitude hypoxia led to significant liver injury and apoptosis, increased the expression levels of p-JNK, BAX and ER stress markers. Salidroside treatment significantly inhibited hypoxia induced ER stress by decreasing the protein expression of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1 alpha). In addition, salidroside treatment also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins p-JNK, TRAF2, BAX, and cleaved caspase 9 and caspase 12, as well as upregulation of Bcl-2. Furthermore, in vitro study found that blocking IRE1 alpha pathway using specific inhibitor STF-083010 subsequently reversed the protective effect of salidroside on liver apoptosis. Taken together, our findings revealed that salidroside exerts protective effects against hypoxia induced liver injury through inhibiting ER stress mediated apoptosis via IRE1 alpha/JNK pathway. (C) 2020 Elsevier Inc. All rights reserved.