mito-TEMPO Attenuates Oxidative Stress and Mitochondrial Dysfunction in Noise-Induced Hearing Loss via Maintaining TFAM-mtDNA Interaction and Mitochondrial Biogenesis

Frontiers in Cellular Neuroscience

Qian Yang¹  Jia-Wei Chen²  Yu-Qiang Lun²  Pei-Heng Lu²  Wei-Long Wang²  Peng-Wei Ma²  Hao Yuan²  Xue-Rui Ding²  Lian-Jun Lu² 

[1] Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China;Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China;

关键词: noise-induced hearing loss;    reactive oxygen species;    mitochondrial transcription factor A;    mitochondrial biogenesis;    sensory hair cells;    rat model;   

DOI  :  10.3389/fncel.2022.803718

来源: DOAJ

【 摘 要 】

The excessive generation of reactive oxygen species (ROS) and mitochondrial damage have been widely reported in noise-induced hearing loss (NIHL). However, the specific mechanism of noise-induced mitochondrial damage remains largely unclear. In this study, we showed that acoustic trauma caused oxidative damage to mitochondrial DNA (mtDNA), leading to the reduction of mtDNA content, mitochondrial gene expression and ATP level in rat cochleae. The expression level and mtDNA-binding function of mitochondrial transcription factor A (TFAM) were impaired following acoustic trauma without affecting the upstream PGC-1α and NRF-1. The mitochondria-target antioxidant mito-TEMPO (MT) was demonstrated to enter the inner ear after the systemic administration. MT treatment significantly alleviated noise-induced auditory threshold shifts 3d and 14d after noise exposure. Furthermore, MT significantly reduced outer hair cell (OHC) loss, cochlear ribbon synapse loss, and auditory nerve fiber (ANF) degeneration after the noise exposure. In addition, we found that MT treatment effectively attenuated noise-induced cochlear oxidative stress and mtDNA damage, as indicated by DHE, 4-HNE, and 8-OHdG. MT treatment also improved mitochondrial biogenesis, ATP generation, and TFAM-mtDNA interaction in the cochlea. These findings suggest that MT has protective effects against NIHL via maintaining TFAM-mtDNA interaction and mitochondrial biogenesis based on its ROS scavenging capacity.

【 授权许可】

Unknown