通过Ras/JNK信号通路,ARC保护耳毛细胞免受新菌素诱导的耳毒性
Xiaoyu Yu1, Hanbing Gao2, Jie Zhang3
1Department of Otolaryngology, Hangzhou First People's Hospital, School of Medicine, Affiliated to Westlake University, Hangzhou, Zhejiang, China; The Fourth school of Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Toxicology letters
|December 12, 2024
概括
具有酶招募域 (ARC) 的亡抑制剂通过Ras/JNK通路减少亡,保护头发细胞免受菌素损伤. 这为预防药物诱导的耳毒性和耳毛细胞死亡提供了新的策略.
科学领域:
- 耳毒性研究研究
- 细胞和分子生物学是细胞和分子生物学.
- 信号通道的信号通道.
背景情况:
- 尼奥米是一种常见的耳毒药物,会导致头发细胞受损.
- 具有酶招募域 (ARC) 的亡抑制剂是细胞存活中的关键蛋白质.
- 了解ARC在毛细胞保护中的作用对于治疗听力损失至关重要.
研究的目的:
- 调查ARC对菌素诱导的头发细胞损伤的保护作用和机制.
- 探索Ras/JNK信号通路在ARC介导保护中的参与.
- 为预防药物诱导的耳毒性提供见解.
主要方法:
- 使用HEI-OC1细胞和基底膜培养物进行实验.
- 使用等离子体转染来调节ARC和Ras表达.
- 评估了细胞活力,细胞亡,切割的caspase-3,p-CREB和p-c-Jun的水平.
主要成果:
- ARC过度表达增强了HEI-OC1细胞活力,并减少了neomycin治疗后的亡.
- 在ARC过度表达细胞中,切割的caspase-3水平降低,而p-CREB增加,p-c-Jun降低.
- 拉斯和JNK抑制降低了ARC表达;拉斯过度表达增加了ARC表达.
结论:
- 通过Ras/JNK信号通路,ARC通过neomycin诱导的亡保护头发细胞.
- ARC作为一种防护因子,可以防止neomycin诱导的耳毒性.
- 研究结果表明,针对ARC的潜在治疗策略可以用于耳毛细胞的保存.
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