TY - JOUR AB - The aim of the present study was to investigate the underlying mechanisms of autophagy in a gentamicin (GM)-induced ototoxic model, and to establish whether the blocking of autophagy significantly increases the survival of inner ear hair cells. Cochleae were carefully dissected from four day‑old C57BL/6J mice and randomly divided into three groups prior to explant culture: Control (culture medium), GM‑treated (culture medium + GM) and GM + 3-methyladenine (3-MA; culture medium + GM + 3‑MA). Transmission electron microscopy, immunofluorescence and western blotting were performed to observe the expression of the autophagy protein microtubule‑associated protein 1A/B‑light chain 3 in explant cultures treated with GM and the autophagy inhibitor 3‑MA. Administration of GM in in vitro mouse cochlear culture induced apoptosis and the formation of autophagic vesicles and autophagosomes in hair cells. Notably, combined treatment with GM and 3‑MA to block autophagy significantly increased the survival of inner ear hair cells. Furthermore, it was indicated that the simultaneous expression and interaction of Atg12 with Bcl‑2 following GM treatment co‑integrated autophagy with apoptosis in the cochlea. The results of the present study demonstrated that autophagy was involved in GM-induced ototoxicity. Additionally, Atg12 may serve a protective role by binding to Bcl‑2. Therefore, Atg12 may be a potential therapeutic target for the treatment of GM-induced cochlear hair loss. AD - Department of Otorhinolaryngology‑Head and Neck Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China Department of Otorhinolaryngology‑Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, P.R. China State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 210096, P.R. China AU - Ma,Xiaofeng AU - Liu,Yongze AU - Muhammad,Waqas AU - Liu,Dingding AU - Wang,Junguo AU - Zhou,Han AU - Gao,Xia AU - Qian,Xiaoyun DA - 2017/06/01 DO - 10.3892/mmr.2017.6458 EP - 3825 IS - 6 JO - Mol Med Rep KW - autophagy gentamicin ototoxicity cochlea PY - 2017 SN - 1791-2997 1791-3004 SP - 3819 ST - Autophagy-related protein 12 associates with anti-apoptotic B cell lymphoma-2 to promote apoptosis in gentamicin-induced inner ear hair cell loss T2 - Molecular Medicine Reports TI - Autophagy-related protein 12 associates with anti-apoptotic B cell lymphoma-2 to promote apoptosis in gentamicin-induced inner ear hair cell loss UR - https://doi.org/10.3892/mmr.2017.6458 VL - 15 ER -