Rescue of auditory hair cells from ototoxicity by CEP-11004, an inhibitor of the JNK signaling pathway
Rescue of auditory hair cells from ototoxicity by CEP-11004, an inhibitor of the JNK signaling pathway
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DOI：
10.1055/s-2002-36100
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发表时间：
2002-12-01
影响因子：
1
通讯作者：
Ryan, AF
中科院分区：
文献类型：
--
作者：
Bodmer, D;Brors, D;Ryan, AF
毛细胞 (HC) 是耳蜗中最脆弱的元素，其损伤是感音神经性听力损失 (SNHL) 的最常见原因。了解导致 HC 死亡的细胞内事件是制定保护策略的关键。最近，研究表明，HC 中的 c-Jun-N 末端激酶 (JNK) 通路在氨基糖苷类药物的作用下被激活，而 CEP-1347（一种 JNK 信号通路抑制剂）可保护 HC 免受耳毒性 [1]。我们研究了该信号通路的另一种抑制剂 (CEP-11004)，它能够在体外保护 HC 免受氨基糖苷类耳毒性。将来自 p5 大鼠基底轮的柯蒂器官外植体维持在组织培养物中并用 CEP-11004 处理 12 小时。然后他们接受 CEP-11004 加庆大霉素治疗 72 小时。与单独使用庆大霉素相比，观察到的 HC 死亡显着减少。单独使用 CEP-11004 对 HC 没有影响。我们得出结论，JNK 信号通路在氨基糖苷类耳毒性信号传导中发挥作用。
The hair cells (HCs) are the most vulnerable elements in the cochlea and damage to them is the most common cause of sensorineural hearing loss (SNHL). Understanding the intracellular events that lead to the death of HCs is a key to developing protective strategies. Recently, it has been shown that the c-Jun-N-terminal kinase (JNK) pathway is activated in HCs in response to aminoglycosides and CEP-1347, an inhibitor of the JNK signaling pathway protected HCs from ototoxicity [1]. We have studied another inhibitor (CEP-11004) of this signaling pathway in its ability to protect HCs from aminoglycoside ototoxicity in vitro. Organ of Corti explants from p5 rat basal turns were maintained in tissue culture and treated with CEP-11004 for 12 hours. They were then treated with CEP-11004 plus gentamicin for 72 hours. Significantly less HC death was observed compared to gentamicin alone. CEP-11004 alone had no effect on HCs. We conclude that the JNK signaling pathway plays a role in aminoglycoside ototoxicity signaling.