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钙蛋白酶2介导的凋亡诱导因子下调损害噪声诱导的螺旋神经节神经元变性中的线粒体功能。

Calpain2-mediated downregulation of apoptosis-inducing factors impairs mitochondrial function in noise-induced spiral ganglion neuron degeneration.

作者信息

Zhong-Jia Ding, Ren-Feng Wang, Wen-Juan Mi, Yin Wang, Ding-Jun Zha

机构信息

Department of Otolaryngology, Xijing Hospital, Air Force Military Medical University, No. 15 Changle Road, Xi'an, Shaanxi, China.

Department of Ultrasound Medicine, Daxing Hospital, No. 6 Daxing Road, Xi'an, Shaanxi, China.

出版信息

IBRO Neurosci Rep. 2025 Aug 5;19:372-380. doi: 10.1016/j.ibneur.2025.07.013. eCollection 2025 Dec.

Abstract

Noise-induced hearing loss can lead to degeneration of spiral ganglion neurons (SGN), resulting in impairment of auditory signalling. However, the specific mechanism is unclear. In our study, we investigated the function of mitochondrial activity following noise exposure. Findings revealed a reduction in ATP synthesis and alterations in the levels of mitochondrial electron transport chain complexes II, Ⅲ, IV and complex I subunit ND3 reduction by the seventh day post-noise exposure. These findings indicate that SGN mitochondrial dysfunction can impair SGN function. This is further demonstrated by the reduced expression of the mitochondrial marker protein Tom20 and apoptosis-inducing factor (AIF) showed inner membrane but not outer membrane resulted in changes in mitochondrial ETC complexes. And the findings of calpain 2 but not calpain 1 high expression was accompanied in AIF reduction, suggesting AIF has not yet caused SGN deaths. Calpain 2 regulated decreased expression of AIF may relieve the low function of mitochondrion in SGN after noise.

摘要

噪声性听力损失可导致螺旋神经节神经元(SGN)变性,从而损害听觉信号传导。然而,具体机制尚不清楚。在我们的研究中,我们调查了噪声暴露后线粒体活性的功能。研究结果显示,噪声暴露后第7天,ATP合成减少,线粒体电子传递链复合物II、III、IV水平发生改变,复合物I亚基ND3减少。这些发现表明,SGN线粒体功能障碍会损害SGN功能。线粒体标记蛋白Tom20表达降低以及凋亡诱导因子(AIF)显示内膜而非外膜导致线粒体ETC复合物发生变化,进一步证明了这一点。并且钙蛋白酶2而非钙蛋白酶1高表达的结果伴随着AIF减少,表明AIF尚未导致SGN死亡。钙蛋白酶2调节AIF表达降低可能会缓解噪声后SGN中线粒体的低功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ed/12356315/b6f357d92409/gr1.jpg

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