Liang Wenqi, Zhao Chunli, Chen Zhongrui, Yang Zijing, Liu Ke, Gong Shusheng
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Front Cell Dev Biol. 2021 Nov 18;9:766512. doi: 10.3389/fcell.2021.766512. eCollection 2021.
Mitochondrial oxidative stress is involved in hair cell damage caused by noise-induced hearing loss (NIHL). Sirtuin-3 (SIRT3) plays an important role in hair cell survival by regulating mitochondrial function; however, the role of SIRT3 in NIHL is unknown. In this study, we used 3-TYP to inhibit SIRT3 and found that this inhibition aggravated oxidative damage in the hair cells of mice with NIHL. Moreover, 3-TYP reduced the enzymatic activity and deacetylation levels of superoxide dismutase 2 (SOD2). Subsequently, we administered adeno-associated virus-SIRT3 to the posterior semicircular canals and found that SIRT3 overexpression significantly attenuated hair cell injury and that this protective effect of SIRT3 could be blocked by 2-methoxyestradiol, a SOD2 inhibitor. These findings suggest that insufficient SIRT3/SOD2 signaling leads to mitochondrial oxidative damage resulting in hair cell injury in NIHL. Thus, ameliorating noise-induced mitochondrial redox imbalance by intervening in the SIRT3/SOD2 signaling pathway may be a new therapeutic target for hair cell injury.
线粒体氧化应激参与噪声性听力损失（NIHL）所致的毛细胞损伤。沉默调节蛋白3（SIRT3）通过调节线粒体功能在毛细胞存活中发挥重要作用；然而，SIRT3在NIHL中的作用尚不清楚。在本研究中，我们使用3-三氟丙酮酸（3-TYP）抑制SIRT3，发现这种抑制加重了NIHL小鼠毛细胞的氧化损伤。此外，3-TYP降低了超氧化物歧化酶2（SOD2）的酶活性和去乙酰化水平。随后，我们将腺相关病毒-SIRT3注射到后半规管，发现SIRT3过表达显著减轻了毛细胞损伤，并且SIRT3的这种保护作用可被SOD2抑制剂2-甲氧基雌二醇阻断。这些发现表明，SIRT3/SOD2信号不足导致线粒体氧化损伤，从而引起NIHL中的毛细胞损伤。因此，通过干预SIRT3/SOD2信号通路改善噪声诱导的线粒体氧化还原失衡可能是毛细胞损伤的一个新的治疗靶点。
