ABCC1 deficiency potentiated noise-induced hearing loss in mice by impairing cochlear antioxidant capacity

Jing Liu; Yijiang Bai; Yong Feng; Xianlin Liu; Bo Pang; Shuai Zhang; Mengzhu Jiang; Anhai Chen; Huping Huang; Yongjia Chen; Jie Ling; Lingyun Mei

Redox Biology (Aug 2024)

ABCC1 deficiency potentiated noise-induced hearing loss in mice by impairing cochlear antioxidant capacity

Jing Liu,
Yijiang Bai,
Yong Feng,
Xianlin Liu,
Bo Pang,
Shuai Zhang,
Mengzhu Jiang,
Anhai Chen,
Huping Huang,
Yongjia Chen,
Jie Ling,
Lingyun Mei

Affiliations

Jing Liu: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Yijiang Bai: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Yong Feng: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Otolaryngology-Head and Neck Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China
Xianlin Liu: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Bo Pang: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
Shuai Zhang: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Mengzhu Jiang: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Anhai Chen: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Huping Huang: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Yongjia Chen: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
Jie Ling: Medical Functional Experiment Center, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Corresponding author.
Lingyun Mei: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Corresponding author.

Journal volume & issue: Vol. 74
p. 103218

Abstract

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The ABCC1 gene belongs to the ATP-binding cassette membrane transporter superfamily, which plays a crucial role in the efflux of various endogenous and exogenous substances. Mutations in ABCC1 can result in autosomal dominant hearing loss. However, the specific roles of ABCC1 in auditory function are not fully understood. Through immunofluorescence, we found that ABCC1 was expressed in microvascular endothelial cells (ECs) of the stria vascularis (StV) in the murine cochlea. Then, an Abcc1 knockout mouse model was established by using CRISPR/Cas9 technology to elucidate the role of ABCC1 in the inner ear. The ABR threshold did not significantly differ between WT and Abcc1−/− mice at any age studied. After noise exposure, the ABR thresholds of the WT and Abcc1−/− mice were significantly elevated. Interestingly, after 14 days of noise exposure, ABR thresholds largely returned to pre-exposure levels in WT mice but not in Abcc1−/− mice. Our subsequent experiments showed that microvascular integrity in the StV was compromised and that the number of outer hair cells and the number of ribbons were significantly decreased in the cochleae of Abcc1−/− mice post-exposure. Besides, the production of ROS and the accumulation of 4-HNE significantly increased. Furthermore, StV microvascular ECs were cultured to elucidate the role of ABCC1 in these cells under glucose oxidase challenge. Notably, 30 U/L glucose oxidase (GO) induced severe oxidative stress damage in Abcc1−/− cells. Compared with WT cells, the ROS and 4-HNE levels and the apoptotic rate were significantly elevated in Abcc1−/− cells. In addition, the reduced GSH/GSSG ratio was significantly decreased in Abcc1−/− cells after GO treatment. Taken together, Abcc1−/− mice are more susceptible to noise-induced hearing loss, possibly because ABCC1 knockdown compromises the GSH antioxidant system of StV ECs. The exogenous antioxidant N-acetylcysteine (NAC) may protect against oxidative damage in Abcc1−/− murine cochleae and ECs.

Published in Redox Biology

ISSN: 2213-2317 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.journals.elsevier.com/redox-biology/

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