Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model
Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model
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顺铂诱导的耳毒性大鼠模型中内质网应激参与耳蜗细胞凋亡
DOI：
10.1159/000480346
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发表时间：
2017-01-01
影响因子：
1.6
通讯作者：
Xiao, Hongjun
中科院分区：
文献类型：
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作者：
Zong, Shimin;Liu, Tianyi;Xiao, Hongjun
当过多的不正确折叠的蛋白质在内质网腔中积累时，内质网（ER）应激出现。当ER应激发生时，未折叠蛋白反应（UPR）随后被激活以恢复ER蛋白稳态。然而，严重的ER应激导致细胞凋亡。最近的研究表明，顺铂的细胞毒性可能与ER应激有关。本研究的目的是确定是否ER应激参与耳蜗细胞凋亡在顺铂诱导的耳毒性大鼠模型，并确定ER应激和听力损失之间的可能关系。我们的结果表明，顺铂处理上调了耳蜗细胞中活性半胱氨酸蛋白酶-12的表达，这表明顺铂诱导了ER特异性细胞凋亡的激活。C/EBP同源蛋白（CHOP）和切割的caspase-9的表达增加表明，严重的ER应激和顺铂处理大鼠耳蜗细胞中的细胞凋亡之间的密切关系。此外，我们发现，牛磺熊去氧胆酸（TUDCA），ER蛋白稳态的促进剂，对顺铂诱导的听力损失有保护作用。这些结果表明，ER应激参与了顺铂诱导的耳蜗细胞凋亡。(C)2017 S. Karger AG，巴塞尔
Endoplasmic reticulum (ER) stress arises when excessive improperly folded proteins accumulate in the ER lumen. When ER stress occurs, the unfolded protein response (UPR) is subsequently activated to restore ER proteostasis. However, severe ER stress leads to apoptosis. Recent studies have suggested that cisplatin cytotoxicity may be related to ER stress. The purpose of this study was to determine whether ER stress participates in cochlear cell apoptosis in a cisplatin-induced ototoxicity rat model and to also determine the possible relationship between ER stress and hearing loss. Our results revealed that treatment with cisplatin upregulated the expression of active caspase-12 in cochlear cells, which is indicative of cisplatin-induced activation of ER-specific apoptosis. Increased expression of C/EBP homologous protein (CHOP) and cleaved caspase-9 suggested a close relationship between severe ER stress and mitochondria-dependent apoptosis in the cochlear cells of cisplatin-treated rats. In addition, we found that tauroursodeoxycholic acid (TUDCA), a promoter of ER proteostasis, had a protective effect on cisplatin-induced hearing loss. These results demonstrate that ER stress is involved in the cisplatin-induced apoptosis of cochlear cells in vivo. (C) 2017 S. Karger AG, Basel