The histone deacetylase inhibitor sodium butyrate protects against noise-induced hearing loss in Guinea pigs
The histone deacetylase inhibitor sodium butyrate protects against noise-induced hearing loss in Guinea pigs
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组蛋白脱乙酰酶抑制剂丁酸钠可预防豚鼠噪音引起的听力损失
DOI：
10.1016/j.neulet.2017.09.036
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发表时间：
2017-11
影响因子：
2.5
通讯作者：
Gong Shu Sheng
中科院分区：
文献类型：
--
作者：
Yang Deng Hua;Xie Jing;Liu Ke;Peng Zhe;Guo Jing Ying;Yu Shu Kui;Wang Guo Peng;Gong Shu Sheng
噪声性听力损失严重影响患者的生活质量。噪声暴露引起的氧化应激是NIHL的重要原因。尽管组蛋白脱乙酰酶(HDAC)抑制剂被证明对NIHL具有保护作用，但其潜在的机制仍不清楚，也不知道它们如何作用于噪声诱导的氧化应激。在本研究中，我们用免疫组织学和Western blotting方法研究了乙酰组蛋白H3(Lys9)(H3-AcK9)、组蛋白脱乙酰基酶1(HDAC1)和氧化应激标志物3-硝基酪氨酸(3-NT)在豚鼠NIHL模型中的表达水平。然后，我们评估了全身应用HDAC抑制剂丁酸钠(SB)对噪声引起的永久性阈值漂移(PTS)、毛细胞(HC)丢失以及上述标志物的变化的影响。结果表明，SB可减轻噪声所致的PTS和外毛细胞的丢失。噪声暴露后，SB可促进H3-AcK9在Hcs和Hensen细胞胞核的表达，抑制HDAC1的表达。此外，SB可减弱噪声诱导的HCS和Hensen‘s细胞3-NT表达的增加。这些发现表明，Sb通过逆转噪声诱导的组蛋白乙酰化失衡和抑制耳蜗Hcs和Hensen细胞的氧化应激来保护NIHL。SB治疗可能是预防和治疗NIHL的一种潜在策略。
Noise-induced hearing loss (NIHL) severely impacts the quality of life of affected individuals. Oxidative stress resulting from noise exposure is a significant cause of NIHL. Although histone deacetylase (HDAC) inhibitors were shown to protect against NIHL, the underlying mechanism remains unclear, and it is not known how they act on noise-induced oxidative stress. In the current study, we investigated the expression levels of acetyl-histone H3 (Lys9) (H3-AcK9), histone deacetylase 1 (HDAC1), and 3-nitrotyrosine (3-NT), an oxidative stress marker, in a guinea pig model of NIHL using immunohistology and Western blotting. We then assessed the effects of systemic administration of the HDAC inhibitor, sodium butyrate (SB), on noise-induced permanent threshold shifts (PTS), hair cell (HC) loss, and changes in the above mentioned markers. The results showed that SB attenuated noise-induced PTS and outer hair cell loss. SB treatment promoted H3-AcK9 expression and repressed HDAC1 expression in the nuclei of HCs and Hensen's cells after noise exposure. Furthermore, SB attenuated the noise-induced increase of 3-NT expression in HCs and Hensen's cells. These findings suggest that SB protects against NIHL by reversing the noise-induced histone acetylation imbalance and inhibiting oxidative stress in cochlear HCs and Hensen's cells. SB treatment may represent a potential strategy to prevent and treat NIHL.
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DOI：
10.3390/ijerph7103730
发表时间：
2010-10
影响因子：
--
作者：
Seidman MD;Standring RT
通讯作者：
Standring RT
DOI：
10.3390/ijerph7083071
发表时间：
2010-08
影响因子：
--
作者：
Mazurek B;Olze H;Haupt H;Szczepek AJ
通讯作者：
Szczepek AJ
影响因子：
2.6
作者：
Gomaa, Mohammed Abdel Motaal;Elmagd, Manal Hassan Abo;Kader, Rafeek Mohammed Abdel
通讯作者：
Kader, Rafeek Mohammed Abdel
影响因子：
--
作者：
Kamogashira T;Fujimoto C;Yamasoba T
通讯作者：
Yamasoba T
DOI：
10.1007/s101620020028
发表时间：
2002-09-01
期刊：
JARO
影响因子：
--
作者：
Wang, Y;Hirose, K;Liberman, MC
通讯作者：
Liberman, MC