Oncotarget

Research Papers:

Inhibition of ARC decreases the survival of HEI-OC-1 cells after neomycin damage in vitro

Ming Guan, Qiaojun Fang, Zuhong He, Yong Li, Fuping Qian, Xiaoyun Qian, Ling Lu, Xiaoli Zhang, Dingding Liu, Jieyu Qi, Shasha Zhang, Mingliang Tang, Xia Gao and Renjie Chai _

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Oncotarget. 2016; 7:66647-66659. https://doi.org/10.18632/oncotarget.11336

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Abstract

Ming Guan1,2,3, Qiaojun Fang4,5, Zuhong He4,5, Yong Li1,2, Fuping Qian4,5, Xiaoyun Qian3,6, Ling Lu3,6, Xiaoli Zhang6, Dingding Liu6, Jieyu Qi4,5, Shasha Zhang4,5, Mingliang Tang4,5, Xia Gao3,6, Renjie Chai4,5

1Department of Otolaryngology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, China

2Department of Otolaryngology, Hangzhou First People’s Hospital, Hangzhou 310006, China

3Department of Otolaryngology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China

4MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China

5Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China

6Department of Otolaryngology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China

Correspondence to:

Renjie Chai, email: renjiec@seu.edu.cn

Xia Gao, email: xiagaogao@hotmail.com

Keywords: cochlea, hair cell, apoptosis, reactive oxygen species, mitochondrial function

Received: April 06, 2016     Accepted: August 10, 2016     Published: August 20, 2016

ABSTRACT

Hearing loss is a common sensory disorder mainly caused by the loss of hair cells (HCs). Noise, aging, and ototoxic drugs can all induce apoptosis in HCs. Apoptosis repressor with caspase recruitment domain(ARC) is a key factor in apoptosis that inhibits both intrinsic and extrinsic apoptosis pathways; however, there have been no reports on the role of ARC in HC loss in the inner ear. In this study, we used House Ear Institute Organ of Corti 1 (HEI-OC-1) cells, which is a cochlear hair-cell-like cell line, to investigate the role of ARC in aminoglycoside-induced HC loss. ARC was expressed in the cochlear HCs as well as in the HEI-OC-1 cells, but not in the supporting cells, and the expression level of ARC in HCs was decreased after neomycin injury in both cochlear HCs and HEI-OC-1 cells, suggesting that reduced levels of ARC might correlate with neomycin-induced HC loss. We inhibited ARC expression using siRNA and found that this significantly increased the sensitivity of HEI-OC-1 cells to neomycin toxicity. Finally, we found that ARC inhibition increased the expression of pro-apoptotic factors, decreased the mitochondrial membrane potential, and increased the level of reactive oxygen species (ROS) after neomycin injury, suggesting that ARC inhibits cell death and apoptosis in HEI-OC-1 cells by controlling mitochondrial function and ROS accumulation. Thus the endogenous anti-apoptotic factor ARC might be a new therapeutic target for the prevention of aminoglycoside-induced HC loss.


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