Chemical chaperone 4-phenylbutyrate prevents hearing loss and cochlear hair cell death in Cdh23(erl/erl) mutant mice
Chemical chaperone 4-phenylbutyrate prevents hearing loss and cochlear hair cell death in Cdh23(erl/erl) mutant mice
复制标题
化学伴侣 4-苯基丁酸酯可预防 Cdh23erl/erl 突变小鼠的听力损失和耳蜗毛细胞死亡
DOI：
10.1097/wnr.0000000000001173
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发表时间：
2019
期刊：
影响因子：
1.7
通讯作者：
Zheng Qingyin
中科院分区：
文献类型：
--
作者：
Li Bo;Zheng Tihua;Yan Caifang;Wang Wenjun;Zhang Jinjin;Zhang Luping;Hu Juan;Zhang Li;Wan Yuzhu;Zhang Minyan;Zheng Qingyin
我们先前开发了Cdh 23 erl/erl突变小鼠（erl小鼠）作为耳保护药物评价的听力损失模型，并表明erl突变导致与内质网（ER）应激诱导的耳蜗毛细胞凋亡相关的听力损失。靶向ER应激的小分子化学伴侣4-苯基丁酸酯（4PBA）发挥神经保护作用。为了评估4PBA是否发挥耳保护作用，我们从出生后第7天至12周每天给erl小鼠腹腔注射4PBA。我们的研究结果表明，治疗与4PBA显着减轻听力损失和抑制毛细胞死亡的erl小鼠。此外，ER应激相关蛋白被4PBA处理下调。我们的研究表明，4PBA发挥耳保护作用，这提供了重新利用药物进行耳保护的潜力。
We previously developed Cdh23 erl/erl mutant mice (erl mice) as a model of hearing loss for otoprotective drug evaluation and showed that the erl mutation leads to hearing loss related to endoplasmic reticulum (ER) stress-induced cochlear hair cell apoptosis. Small molecular chemical chaperones, 4-phenylbutyrate (4PBA), targeting ER stress exert a neuroprotective effect. To evaluate whether 4PBA exerts an otoprotective effect, we intraperitoneally injected erl mice with 4PBA daily from postnatal age day 7 up to 12 weeks. Our results showed that treatment with 4PBA significantly alleviated hearing loss and suppressed hair cell death in erl mice. In addition, ER stress-related proteins were downregulated by 4PBA treatment. Our study showed that 4PBA exerts an otoprotective effect, which provides the potential to repurpose the drug for otoprotection.