Blebbistatin Inhibits Neomycin-Induced Apoptosis in Hair Cell-Like HEI-OC-1 Cells and in Cochlear Hair Cells
Blebbistatin Inhibits Neomycin-Induced Apoptosis in Hair Cell-Like HEI-OC-1 Cells and in Cochlear Hair Cells
复制标题
布雷他汀抑制新霉素诱导的毛细胞样 HEI-OC-1 细胞和耳蜗毛细胞凋亡
DOI：
10.3389/fncel.2019.00590
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发表时间：
2020-02-05
影响因子：
5.3
通讯作者：
Chai, Renjie
中科院分区：
文献类型：
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作者：
Gao, Song;Cheng, Cheng;Chai, Renjie
老化、噪声和耳毒性药物引起的毛细胞(HC)丢失是感音神经性听力损失的主要原因。氨基糖苷类抗生素是临床上常用的抗生素，但由于氧自由基的积聚和随后的诱导HC细胞凋亡，这些抗生素往往会产生耳毒性副作用。Blebbistatin是一种肌球蛋白II抑制剂，调节微管组装和肌球蛋白-肌动蛋白相互作用，大多数研究都集中在它调节心脏或膀胱收缩的能力上。Blebbistatin通过调节细胞骨架结构和减少ROS的积累，可以防止许多不同类型的细胞发生凋亡。然而，目前还没有关于blbbistatin在HC细胞凋亡中的作用的报道。在这项研究中，我们发现，博莱比星的存在显著抑制了新霉素诱导的HC样HEI-OC-1细胞的凋亡。我们还发现，Blebbistatin处理显著增加了新霉素暴露后HC-like HEI-OC-1细胞和耳蜗骨细胞线粒体膜电位，减少了ROS的积聚，抑制了促凋亡基因的表达。同时，Blebbistatin对Hcs和耳蜗螺旋神经节神经元之间的突触连接具有保护作用。本研究表明，Blebbistatin可以维持线粒体功能，降低ROS水平，从而维持新霉素暴露后Hcs的活性和内耳的神经功能，提示Blebbistatin在保护耳毒性药物引起的HC丢失方面具有潜在的临床应用价值。
Aging, noise, and ototoxic drug-induced hair cell (HC) loss are the major causes of sensorineural hearing loss. Aminoglycoside antibiotics are commonly used in the clinic, but these often have ototoxic side effects due to the accumulation of oxygen-free radicals and the subsequent induction of HC apoptosis. Blebbistatin is a myosin II inhibitor that regulates microtubule assembly and myosin–actin interactions, and most research has focused on its ability to modulate cardiac or urinary bladder contractility. By regulating the cytoskeletal structure and reducing the accumulation of reactive oxygen species (ROS), blebbistatin can prevent apoptosis in many different types of cells. However, there are no reports on the effect of blebbistatin in HC apoptosis. In this study, we found that the presence of blebbistatin significantly inhibited neomycin-induced apoptosis in HC-like HEI-OC-1 cells. We also found that blebbistatin treatment significantly increased the mitochondrial membrane potential (MMP), decreased ROS accumulation, and inhibited pro-apoptotic gene expression in both HC-like HEI-OC-1 cells and explant-cultured cochlear HCs after neomycin exposure. Meanwhile, blebbistatin can protect the synaptic connections between HCs and cochlear spiral ganglion neurons. This study showed that blebbistatin could maintain mitochondrial function and reduce the ROS level and thus could maintain the viability of HCs after neomycin exposure and the neural function in the inner ear, suggesting that blebbistatin has potential clinic application in protecting against ototoxic drug-induced HC loss.