P2X7 receptor is required for the ototoxicity caused by aminoglycoside in developing cochlear hair cells

Cheng Cheng; Jiaoyao Ma; Xiaoling Lu; Panpan Zhang; Xiaohan Wang; Luo Guo; Peifan Li; Ying Wei; Geng-Lin Li; Xia Gao; Yuqiu Zhang; Renjie Chai; Huawei Li; Shan Sun

Neurobiology of Disease (Jul 2023)

P2X7 receptor is required for the ototoxicity caused by aminoglycoside in developing cochlear hair cells

Cheng Cheng,
Jiaoyao Ma,
Xiaoling Lu,
Panpan Zhang,
Xiaohan Wang,
Luo Guo,
Peifan Li,
Ying Wei,
Geng-Lin Li,
Xia Gao,
Yuqiu Zhang,
Renjie Chai,
Huawei Li,
Shan Sun

Affiliations

Cheng Cheng: Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), No.321 Zhongshan Road,Nanjing 210008, China
Jiaoyao Ma: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China
Xiaoling Lu: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China
Panpan Zhang: State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China
Xiaohan Wang: State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China
Luo Guo: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China
Peifan Li: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China
Ying Wei: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, China
Geng-Lin Li: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China
Xia Gao: Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), No.321 Zhongshan Road,Nanjing 210008, China
Yuqiu Zhang: State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China; Correspondence to: Yuqiu Zhang, Institutes of Brain Science, Fudan University, Shanghai 200031, China.
Renjie Chai: State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China; Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, 100069 Beijing, China; Correspondence to: Renjie Chai, School of Life Science and Technology, Southeast University, Nanjing 200031, China.
Huawei Li: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China; Fudan University School of Basic Medical Sciences, NHC Key Laboratory of Hearing Medicine, Institutes of Biomedical Sciences, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China; Correspondence to: Huawei Li, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.
Shan Sun: ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China; Correspondence to: Shan Sun, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.

Journal volume & issue: Vol. 183
p. 106176

Abstract

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Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin–Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7−/− mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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