c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro
作者
Yu, XY;Liu, WW;Fan, ZM;Qian, FP;Zhang, DG;Han, YC;Xu, L;Sun, GY;Qi, JY;Zhang, SS;Tang, ML;Li, JF;Chai, RJ;Wang, HB
作者单位
[Yu, Xiaoyu; Liu, Wenwen; Fan, Zhaomin; Zhang, Daogong; Han, Yuechen; Xu, Lei; Sun, Gaoying; Li, Jianfeng; Wang, Haibo] Shandong Univ, Shandong Prov Hosp, Otolaryngol Head & Neck Surg, Jinan, Peoples R China.;-;[Yu, Xiaoyu; Liu, Wenwen; Sun, Gaoying; Li, Jianfeng; Wang, Haibo] Shandong Prov Key Lab Otol, Jinan, Peoples R China.;-;[Qian, Fuping; Qi, Jieyu; Zhang, Shasha; Tang, Mingliang; Chai, Renjie] Southeast Univ, Inst Life Sci, Minist Educ, Key Lab Dev Genes & Human Dis, Nanjing 210096, Jiangsu, Peoples R China.;-;[Qian, Fuping; Qi, Jieyu; Zhang, Shasha; Tang, Mingliang; Chai, Renjie] Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China.;-;[Chai, Renjie] Southeast Univ, Zhongda Hosp, Dept Otolaryngol Head & Neck Surg, Nanjing 210096, Jiangsu, Peoples R China.
摘要
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.
关键词
BREAST-CANCER CELLS; INDUCED APOPTOSIS; MYELOID-LEUKEMIA; EXPRESSION; OTOTOXICITY; ACTIVATION; DEATH; GENE; DIFFERENTIATION; PROTECTS
基本信息
