Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model

Copyright © 2020 Guoxia Zhu et al.

Bibliographische Detailangaben
Veröffentlicht in:Neural plasticity. - 1998. - 2020(2020) vom: 01., Seite 8823785
1. Verfasser: Zhu, Guoxia (VerfasserIn)
Weitere Verfasser: Wu, Yongxiang, Qiu, Yang, Tian, Keyong, Mi, Wenjuan, Liu, Xinqin, Chen, Yuanyuan, Jia, Jinwen, Luo, Jiasheng, Lu, Lianjun, Qiu, Jianhua
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Neural plasticity
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Bmi1 protein, rat HSP72 Heat-Shock Proteins Nerve Tissue Proteins Foxo1 protein, rat Superoxide Dismutase-1 EC 1.15.1.1 Polycomb Repressive Complex 1 EC 2.3.2.27
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245 1 0 |a Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model 
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520 |a Sound conditioning (SC) is defined as "toughening" to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Bmi1 protein, rat  |2 NLM 
650 7 |a HSP72 Heat-Shock Proteins  |2 NLM 
650 7 |a Nerve Tissue Proteins  |2 NLM 
650 7 |a Foxo1 protein, rat  |2 NLM 
650 7 |a Superoxide Dismutase-1  |2 NLM 
650 7 |a EC 1.15.1.1  |2 NLM 
650 7 |a Polycomb Repressive Complex 1  |2 NLM 
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700 1 |a Wu, Yongxiang  |e verfasserin  |4 aut 
700 1 |a Qiu, Yang  |e verfasserin  |4 aut 
700 1 |a Tian, Keyong  |e verfasserin  |4 aut 
700 1 |a Mi, Wenjuan  |e verfasserin  |4 aut 
700 1 |a Liu, Xinqin  |e verfasserin  |4 aut 
700 1 |a Chen, Yuanyuan  |e verfasserin  |4 aut 
700 1 |a Jia, Jinwen  |e verfasserin  |4 aut 
700 1 |a Luo, Jiasheng  |e verfasserin  |4 aut 
700 1 |a Lu, Lianjun  |e verfasserin  |4 aut 
700 1 |a Qiu, Jianhua  |e verfasserin  |4 aut 
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