2. Academic Validation
  3. Connexin30-deficient mice increase susceptibility to noise via redox and lactate imbalances

Connexin30-deficient mice increase susceptibility to noise via redox and lactate imbalances

  • Free Radic Biol Med. 2024 Oct 11:225:641-653. doi: 10.1016/j.freeradbiomed.2024.10.280.
Jifang Zhang 1,  Tianyu Gong 1,  Penghui Chen 1,  Jingyi Zhu 1,  Sihan Huang 1,  Yue Li 1,  Guiping Li 2,  Qing Zhang 1,  Maoli Duan 3,  Qiang Song 4,  Jun Yang 5,  Shule Hou 6
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China.
  • 2 Shanghai Jiaotong University School of Medicine, China.
  • 3 Ear Nose and Throat Patient Area, Trauma and Reparative Medicine Theme, Karolinska University Hospital, Stockholm, Sweden; Division of Ear, Nose and Throat Diseases, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
  • 4 Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China. Electronic address: songqiang10006@xinhuamed.com.cn.
  • 5 Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China. Electronic address: yangjun@xinhuamed.com.cn.
  • 6 Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, China; Shanghai Jiaotong University School of Medicine Ear Institute, Shanghai, China. Electronic address: houshule8562@xinhuamed.com.cn.
PMID: 39396580 DOI: 10.1016/j.freeradbiomed.2024.10.280
Abstract

Noise significantly contributes to one-third of the global burden of hearing loss. The intricate interplay of genetic and environmental factors impacts various molecular and cellular processes that lead to noise-induced hearing loss (NIHL). Defective connexin 26 (Cx26) and connexin 30 (Cx30), encoded by Gjb2/Cx26 and Gjb6/Cx30, respectively, are prevalent causes of hereditary deafness. However, the role of Cx30 in the pathogenesis of NIHL remains unclear. Herein, we observed that homozygous Cx30 knockout (Cx30 KO) mice exhibited poorer hearing recovery after noise exposure (97 dB mean sound pressure level for 2 h) and increased susceptibility to noise. In addition to the exacerbation of noise-induced damage to hair cells and synapses, Cx30 KO mice exposed to noise exhibited increased oxidative stress. The 2-(N-(7-nitrobenz-2-oxa-1,3-dia-zol-4-yl) amino)-2-deoxyglucose assay showed a reduction in glucose levels associated with a decrease in gap junctions as well as a reduction in adenosine triphosphate release. Glucose metabolomics analysis further revealed that Cx30 KO mice had elevated lactate and NAD + levels after noise exposure, thus worsening anaerobic oxidation from glycolysis. Our study emphasizes that Cx30-deficient mice increase susceptibility to noise via redox and lactate imbalances in the cochlea.

Keywords

Connexin 30; Glucose metabolism; Lactate; Noise-induced hearing loss; Oxidative stress.

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