Study on the mechanism of the age-related hearing loss and establishment of its preventive treatment

年龄相关性听力损失的机制研究及预防治疗的建立

• 批准号: 20390440
• 负责人: YAMASOBA TATSUYA
• 金额: $ 12.48万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390440/
• 关键词: 老化; 蝸牛; ミトコンドリア; アポトーシス; 難聴; 酸化ストレス; 老化; 蝸牛; ミトコンドリア; アポトーシス; 難聴; 酸化ストレス

Deficiency of vitamin C accelerated presbyacusis (ARHL), whereas supplementation of vitamin C did not attenuate ARHL in C57BL/6 mice. The onset of ARHL was delayed when catalase was over-expressed in mitochondria in C57BL/6 mice. Such attenuation of ARHL was also observed when C57BL/6 mice were given alpha-lipoic acid, CoQ10, or NAC. Expression of Bak significantly decreased in the cochleae of the mice showing attenuation of ARHL. ARHL was significantly attenuated in Bak-deficient mice, but not in Bax-deficient mice. These findings suggest that chronic oxidative stress induced Bak-dependent apoptosis in the cochlear cells, resulting in the development of ARHL.

维生素C的缺乏加速长期（ARHL），而补充维生素C并未减弱C57BL/6小鼠的ARHL。当C57BL/6小鼠的线粒体中过量表达过表达时，ARHL的发作延迟。当C57BL/6小鼠被给予α-硫酸，COQ10或NAC时，还观察到ARHL的这种衰减。 Bak的表达显着降低，显示出ARHL衰减的小鼠的耳蜗。在缺陷的小鼠中，ARHL显着减弱，但在不足的小鼠中没有显着减弱。这些发现表明，慢性氧化应激诱导人工耳蜗中的BAK依赖性凋亡，从而导致ARHL的发展。