SIRT1 protects cochlear hair cell and delays age-related hearing loss via autophagy
| Autor: | Hanqing Lin, Yiqing Zheng, Yongyi Ye, Hao Xiong, Haidi Yang, Zhongwu Su, Yongkang Ou, Yaodong Xu, Jiaqi Pang, Lan Lai, Suijun Chen, Xiaoding Xu, Qiuhong Huang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Autophagosome Aging Programmed cell death Hearing Loss Sensorineural Vesicular Transport Proteins Regulator Autophagy-Related Proteins 03 medical and health sciences 0302 clinical medicine Sirtuin 1 Hair Cells Auditory Autophagy medicine Animals Chemistry General Neuroscience Endoplasmic reticulum Membrane Proteins food and beverages Acetylation Endoplasmic Reticulum Stress Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Organ of Corti Autophagosome membrane Unfolded protein response Neurology (clinical) Geriatrics and Gerontology hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of Aging. 80:127-137 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2019.04.003 |
| Popis: | Age-related hearing loss (AHL) is typically caused by the irreversible death of hair cells (HCs). Autophagy is a constitutive pathway to strengthen cell survival under normal or stress condition. Our previous work suggested that impaired autophagy played an important role in the development of AHL in C57BL/6 mice, although the underlying mechanism of autophagy in AHL still needs to be investigated. SIRT1 as an important regulator involves in AHL and is also a regulator of autophagy. Thus, we hypothesized that the modulation between SIRT1 and autophagy contribute to HC death and the progressive hearing dysfunction in aging. In the auditory cell line HEI-OC1, SIRT1 modulated autophagosome induction because of SIRT1 deacetylating a core autophagy protein ATG9A. The deacetylation of ATG9A not only affects the autophagosome membrane formation but also acts as a sensor of endoplasmic reticulum (ER) stress inducing autophagy. Moreover, the silencing of SIRT1 facilitated cell death via autophagy inhibition, whereas SIRT1 and autophagy activation reversed the SIRT1 inhibition media cell death. Notably, resveratrol, the first natural agonist of SIRT1, altered the organ of Corti autophagy impairment of the 12-month-old C57BL/6 mice and delayed AHL. The activation of SIRT1 modulates the deacetylation status of ATG9A, which acts as a sensor of ER stress, providing a novel perspective in elucidating the link between ER stress and autophagy in aging. Because SIRT1 activation restores autophagy with reduced HC death and hearing loss, it could be used as a strategy to delay AHL. |
| Databáze: | OpenAIRE |
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