Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line

Frontiers in Cellular Neuroscience

Yuexin Cai¹  Suijun Chen¹  Hao Xiong¹  Qiuhong Huang¹  Xueyuan Zhang¹  Haidi Yang¹  Hongyu Chen¹  Maojin Liang¹  Yongkang Ou¹  Yaodong Xu¹  Yiqing Zheng¹  Gui Cheng³  Haiying Jia³  Ting Zhan⁴  Hanqing Lin⁴  Lan Lai⁴  Jiaqi Pang⁴  Zhongwu Su⁴  Xiaoding Xu⁵  Yongyi Ye⁶ 

[1] Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China;Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;Department of Otolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;School of Public Health, Sun Yat-sen University, Guangzhou, China;

关键词: SIRT1;    autophagy;    cisplatin;    cell death;    ototoxicity;   

DOI  :  10.3389/fncel.2018.00515

来源: DOAJ

【 摘 要 】

Cisplatin-induced ototoxicity is one of the major adverse effects in cisplatin chemotherapy, and hearing protective approaches are unavailable in clinical practice. Recent work unveiled a critical role of autophagy in cell survival in various types of hearing loss. Since the excessive activation of autophagy can contribute to apoptotic cell death, whether the activation of autophagy increases or decreases the rate of cell death in CDDP ototoxicity is still being debated. In this study, we showed that CDDP induced activation of autophagy in the auditory cell HEI-OC1 at the early stage. We then used rapamycin, an autophagy activator, to increase the autophagy activity, and found that the cell death significantly decreased after CDDP injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly increased cell death. In accordance with in vitro results, rapamycin alleviated CDDP-induced death of hair cells in zebrafish lateral line and cochlear hair cells in mice. Notably, we found that CDDP-induced increase of Sirtuin 1 (SIRT1) in the HEI-OC1 cells modulated the autophagy function. The specific SIRT1 activator SRT1720 could successfully protect against CDDP-induced cell loss in HEI-OC1 cells, zebrafish lateral line, and mice cochlea. These findings suggest that SIRT1 and autophagy activation can be suggested as potential therapeutic strategies for the treatment of CDDP-induced ototoxicity.

【 授权许可】

Unknown