耳内质网膜应激会导致连素26的降解,与年龄相关的听力损失有关
Xue Bai1, Bing Liao1, Wen-Hui Hu1
1Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.
iScience
|December 1, 2025
概括
与年龄相关的听力损失涉及连素26 (Cx26) 降解. 耳内质网膜 (ER) 的压力会导致Cx26的无化和损失,导致老年小鼠的听力损失.
科学领域:
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 与年龄相关的听力损失 (ARHL) 是一种渐进的听力障碍.
- 尾中Connexin 26 (Cx26) 降解与ARHL病原发生有关.
- 驱动与年龄相关的Cx26降解的分子机制尚未完全理解.
研究的目的:
- 研究与年龄相关的听力损失中Cx26降解的分子机制.
- 分析不同年龄的C57BL/6J小鼠中的Cx26表达模式.
- 为了确定内质网膜 (ER) 应激在Cx26下调中的作用.
主要方法:
- 在不同年龄组的老鼠耳中对Cx26表达的系统分析.
- 在老化耳组织中评估ER压力标志物 (GRP78,PDI).
- 在实验室中使用耳扩展剂的研究来评估ER应激对Cx26水平的影响.
- 检查与ubiquitination相关的蛋白质 (Nedd4,Eps15) 和它们与Cx26.6的同位素化.
主要成果:
- 确认了老鼠尾管中Cx26的年龄相关下调.
- 在老化耳组织中观察到ER压力标志物 (GRP78,PDI) 的同时上调.
- 证明ER压力显著降低了耳扩展器中的Cx26蛋白水平.
- 在ER应激模型中发现,随着Cx26增强了ubiquitination蛋白 (Nedd4,Eps15) 的表达和同位化.
结论:
- Cx26降解是与年龄相关的听力损失的一个关键因素.
- 耳ER应激会诱导Cx26的无处不在.
- 由ER压力介导的基化是老鼠耳中Cx26降解的主要机制.
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