Frontiers in Cellular Neuroscience (Jan 2019)
Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line
- Jiaqi Pang,
- Jiaqi Pang,
- Jiaqi Pang,
- Hao Xiong,
- Hao Xiong,
- Ting Zhan,
- Ting Zhan,
- Gui Cheng,
- Haiying Jia,
- Yongyi Ye,
- Zhongwu Su,
- Zhongwu Su,
- Zhongwu Su,
- Hongyu Chen,
- Hanqing Lin,
- Hanqing Lin,
- Hanqing Lin,
- Lan Lai,
- Lan Lai,
- Lan Lai,
- Yongkang Ou,
- Yongkang Ou,
- Yaodong Xu,
- Yaodong Xu,
- Suijun Chen,
- Suijun Chen,
- Qiuhong Huang,
- Qiuhong Huang,
- Maojin Liang,
- Maojin Liang,
- Yuexin Cai,
- Yuexin Cai,
- Xueyuan Zhang,
- Xueyuan Zhang,
- Xiaoding Xu,
- Xiaoding Xu,
- Yiqing Zheng,
- Yiqing Zheng,
- Haidi Yang,
- Haidi Yang
Affiliations
- Jiaqi Pang
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Jiaqi Pang
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Jiaqi Pang
- 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
- Hao Xiong
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Hao Xiong
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Ting Zhan
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Ting Zhan
- 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
- Gui Cheng
- Department of Otolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Haiying Jia
- Department of Otolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Yongyi Ye
- School of Public Health, Sun Yat-sen University, Guangzhou, China
- Zhongwu Su
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Zhongwu Su
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Zhongwu Su
- 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
- Hongyu Chen
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Hanqing Lin
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Hanqing Lin
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Hanqing Lin
- 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
- Lan Lai
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Lan Lai
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Lan Lai
- 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
- Yongkang Ou
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Yongkang Ou
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Yaodong Xu
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Yaodong Xu
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Suijun Chen
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Suijun Chen
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Qiuhong Huang
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Qiuhong Huang
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Maojin Liang
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Maojin Liang
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Yuexin Cai
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Yuexin Cai
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Xueyuan Zhang
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Xueyuan Zhang
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Xiaoding Xu
- 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
- Xiaoding Xu
- RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Yiqing Zheng
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Yiqing Zheng
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- Haidi Yang
- Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Haidi Yang
- Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China
- DOI
- https://doi.org/10.3389/fncel.2018.00515
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords