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

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

doi:10.18632/oncotarget.11336

Cited by 24 publications

(19 citation statements)

References 36 publications

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“…HEI-OC1 cells, a HC-like cell line, express several molecular markers of cochlear HCs, including calbindin, calmodulin, math1, myosin7a, and prestin28293031, and they are commonly used to study the protection of HCs. We used Myosin 7a as the HC marker, and immunostaining showed that all HEI-OC1 cells could be double labeled by Myosin 7a and c-Myb, demonstrating that c-Myb is expressed in HEI-OC1 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro

Liu

Fan

et al. 2017

Sci Rep

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c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb. We then knocked down c-Myb expression with shRNA transfection in HEI-OC1 cells and found that c-Myb knockdown decreased cell viability, increased expression of pro-apoptotic factors, and enhanced cell apoptosis after neomycin insult. Mechanistic studies revealed that c-Myb knockdown increased cellular levels of reactive oxygen species and decreased Bcl-2 expression, both of which are likely to be responsible for the increased sensitivity of c-Myb knockdown cells to neomycin. This study provides evidence that c-Myb might serve as a new target for the prevention of aminoglycoside-induced HC loss.

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Section: Resultsmentioning

confidence: 99%

c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro

Liu

Fan

et al. 2017

Sci Rep

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“…Ototoxic drugs cause hearing loss by inducing HC apoptosis, primarily by altering the MMP of the mitochondria ( Huang et al, 2000 ; Wu et al, 2002 ; Sun et al, 2015 ; Guan et al, 2016 ; He et al, 2016 ; Yu et al, 2017 ). Mitochondria play an important role in cell metabolism, and aminoglycoside-induced apoptosis is closely related to mitochondrial dysfunction, which leads to decreased MMP and increased ROS ( Joza et al, 2001 ; Chipuk et al, 2004 ; Coffin et al, 2013 ; Sun et al, 2014 , 2015 ; Mei et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage

Zhong

et al. 2020

Front. Cell Dev. Biol.

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Aminoglycoside-induced hair cell (HC) loss is one of the most important causes of hearing loss. After entering the inner ear, aminoglycosides induce the production of high levels of reactive oxygen species (ROS) that subsequently activate apoptosis in HCs. Citicoline, a nucleoside derivative, plays a therapeutic role in central nervous system injury and in neurodegenerative disease models, including addictive disorders, stroke, head trauma, and cognitive impairment in the elderly, and has been widely used in the clinic as an FDA approved drug. However, its effect on auditory HCs remains unknown. Here, we used HC-like HEI-OC-1 cells and whole organ explant cultured mouse cochleae to explore the effect of citicoline on aminoglycoside-induced HC damage. Consistent with previous reports, both ROS levels and apoptosis were significantly increased in neomycin-induced cochlear HCs and HEI-OC-1 cells compared to undamaged controls. Interestingly, we found that co-treatment with citicoline significantly protected against neomycin-induced HC loss in both HEI-OC-1 cells and whole organ explant cultured cochleae. Furthermore, we demonstrated that citicoline could significantly reduce neomycin-induced mitochondrial dysfunction and inhibit neomycin-induced ROS accumulation and subsequent apoptosis. Thus, we conclude that citicoline can protect against neomycin-induced HC loss by inhibiting ROS aggregation and thus preventing apoptosis in HCs, and this suggests that citicoline might serve as a potential therapeutic drug in the clinic to protect HCs.

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“…Several previous studies have shown that HC loss induced by ototoxic drugs is commonly associated with ROS accumulation, which induces mitochondrial depolarization and initiates apoptosis ( Marcotti et al, 2005 ; Mcfarland et al, 2007 ; Shan et al, 2014 ; Guan et al, 2016 ; He et al, 2016 ; Liu et al, 2016 ; Yu et al, 2017 ). We evaluated the levels of mitochondrial ROS in HEI-OC1 cells after cisplatin and H 2 O 2 treatment and found that the ROS level was significantly decreased after MA2 treatment compared to the cisplatin and H 2 O 2 treatment group ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

Meclofenamic Acid Reduces Reactive Oxygen Species Accumulation and Apoptosis, Inhibits Excessive Autophagy, and Protects Hair Cell-Like HEI-OC1 Cells From Cisplatin-Induced Damage

Song

et al. 2018

Front. Cell. Neurosci.

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Hearing loss is the most common sensory disorder in humans, and a significant number of cases is due to the ototoxicity of drugs such as cisplatin that cause hair cell (HC) damage. Thus, there is great interest in finding agents and mechanisms that protect HCs from ototoxic drug damage. It has been proposed that epigenetic modifications are related to inner ear development and play a significant role in HC protection and HC regeneration; however, whether the m6A modification and the ethyl ester form of meclofenamic acid (MA2), which is a highly selective inhibitor of FTO (fatmass and obesity-associated enzyme, one of the primary human demethylases), can affect the process of HC apoptosis induced by ototoxic drugs remains largely unexplored. In this study, we took advantage of the HEI-OC1 cell line, which is a cochlear HC-like cell line, to investigate the role of epigenetic modifications in cisplatin-induced cell death. We found that cisplatin injury caused reactive oxygen species accumulation and increased apoptosis in HEI-OC1 cells, and the cisplatin injury was reduced by co-treatment with MA2 compared to the cisplatin-only group. Further investigation showed that MA2 attenuated cisplatin-induced oxidative stress and apoptosis in HEI-OC1 cells. We next found that the cisplatin-induced upregulation of autophagy was significantly inhibited after MA2 treatment, indicating that MA2 inhibited the cisplatin-induced excessive autophagy. Our findings show that MA2 has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-induced ototoxicity.

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

Cited by 24 publications

References 36 publications

c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro

c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro

Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage

Meclofenamic Acid Reduces Reactive Oxygen Species Accumulation and Apoptosis, Inhibits Excessive Autophagy, and Protects Hair Cell-Like HEI-OC1 Cells From Cisplatin-Induced Damage

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