title: Inhibition of ARC decreases the survival of HEI-OC-1 cells after neomycin damage in vitro.
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.
authors.affiliation: Department of Otolaryngology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, China.|Department of Otolaryngology, Hangzhou First People's Hospital, Hangzhou 310006, China.|Department of Otolaryngology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Fang
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Zuhong
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Otolaryngology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, China.|Department of Otolaryngology, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Fuping
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Otolaryngology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China.|Department of Otolaryngology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Otolaryngology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China.|Department of Otolaryngology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Otolaryngology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Qi
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Otolaryngology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China.|Department of Otolaryngology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D009124:Muscle Proteins; C491787:Nol3 protein, mouse; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D009355:Neomycin
keywords: apoptosis; cochlea; hair cell; mitochondrial function; reactive oxygen species