Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network.
Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network.
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DOI：
10.1016/j.celrep.2020.108431
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发表时间：
2020-11-24
期刊：
影响因子：
8.8
通讯作者：
Savas JN
中科院分区：
文献类型：
--
作者：
Jongkamonwiwat N;Ramirez MA;Edassery S;Wong ACY;Yu J;Abbott T;Pak K;Ryan AF;Savas JN
暴露于过多的声音会通过复杂的机制引起噪声性听力损失，这是一种常见的尚未解决的神经系统疾病。我们通过蛋白质组学和功能分析来研究噪音对耳蜗的影响。定量蛋白质组学表明，暴露于噪音会导致蛋白质毒性。我们鉴定并确认了数百种积累的蛋白质，包括细胞骨架蛋白和蛋白质静止网络的几个节点。转录组学分析显示，编码这些蛋白质的基因子集在噪声暴露后也急剧增加，包括许多蛋白酶体亚基。暴露于过量噪声后，全球耳蜗蛋白泛素化水平增加，我们绘制了许多翻译后修饰的赖氨酸残基。一些胶原蛋白的丰度降低，Col9a1特异性定位于柱状细胞头。恢复两周后，耳蜗选择性地提高蛋白质合成机制的丰度。我们报告，听觉系统的过度刺激驱动一个强大的耳蜗蛋白毒性应激反应。Jongkamonwiwat等人在噪声暴露后立即对小鼠耳蜗提取物进行了定量蛋白质组学分析。他们发现许多蛋白质水平升高，蛋白质平衡网络被激活。在恢复过程中，核糖体蛋白上调。这些结果表明，大噪声引起的听力损失可导致耳蜗蛋白毒性。
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that a subset of the genes encoding these proteins also increases acutely after noise exposure, including numerous proteasome subunits. Global cochlear protein ubiquitylation levels build up after exposure to excess noise, and we map numerous posttranslationally modified lysines residues. Several collagen proteins decrease in abundance, and Col9a1 specifically localizes to pillar cell heads. After two weeks of recovery, the cochlea selectively elevates the abundance of the protein synthesis machinery. We report that overstimulation of the auditory system drives a robust cochlear proteotoxic stress response. Jongkamonwiwat et al. perform quantitative proteomic analysis of mouse cochlear extracts immediately after noise exposure. They discover that many proteins have elevated levels and the proteostasis network is activated. During recovery, ribosomal proteins are upregulated. These results show that loud noise causing hearing loss results in cochlear proteotoxicity.
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影响因子：
4.5
作者：
Hertzano R;Elkon R;Kurima K;Morrisson A;Chan SL;Sallin M;Biedlingmaier A;Darling DS;Griffith AJ;Eisenman DJ;Strome SE
通讯作者：
Strome SE
影响因子：
5.3
作者：
Kujawa, SG;Liberman, MC
通讯作者：
Liberman, MC
影响因子：
5.3
作者：
Hickox, Ann E.;Wong, Ann C. Y.;Savas, Jeffrey N.
通讯作者：
Savas, Jeffrey N.
影响因子：
0.7
作者：
Kim, Dong-Kee;Park, Yooyeon;Park, Shi-Nae
通讯作者：
Park, Shi-Nae
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC