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细胞外信号调节激酶2(ERK2)介导内毛细胞存活并降低噪声性听力损失的易感性。

ERK2 mediates inner hair cell survival and decreases susceptibility to noise-induced hearing loss.

作者信息

Kurioka Takaomi, Matsunobu Takeshi, Satoh Yasushi, Niwa Katsuki, Endo Shogo, Fujioka Masato, Shiotani Akihiro

机构信息

Department of Otolaryngology, National Defense Medical College, Saitama, Japan.

Department of Anesthesiology, National Defense Medical College, Saitama, Japan.

出版信息

Sci Rep. 2015 Nov 18;5:16839. doi: 10.1038/srep16839.

Abstract

Extracellular signal-regulated kinase (ERK) is a member of the family of mitogen-activated protein kinases (MAPKs) and coordinately regulates a multitude of cellular processes. In response to a variety of extracellular stimuli, phosphorylation of both threonine and tyrosine residues activates ERK. Recent evidence indicates that ERK is activated in response to cellular stress such as acoustic trauma. However, the specific role of ERK isoforms in auditory function is not fully understood. Here, we show that the isoform ERK2 plays an important role in regulating hair cell (HC) survival and noise-induced hearing loss (NIHL) in mice (C57BL/6J). We found that conditional knockout mice deficient for Erk2 in the inner ear HCs had hearing comparable to control mice and exhibited no HC loss under normal conditions. However, we found that these knockout mice were more vulnerable to noise and had blunted recovery from NIHL compared to control mice. Furthermore, we observed a significantly lower survival rate of inner hair cells in these mice compared to control mice. Our results indicate that ERK2 plays important roles in the survival of HC in NIHL.

摘要

细胞外信号调节激酶(ERK)是丝裂原活化蛋白激酶(MAPK)家族的成员,可协同调节多种细胞过程。响应多种细胞外刺激时,苏氨酸和酪氨酸残基的磷酸化会激活ERK。最近的证据表明,ERK会响应诸如声创伤等细胞应激而被激活。然而,ERK亚型在听觉功能中的具体作用尚未完全明确。在此,我们表明ERK2亚型在调节小鼠(C57BL/6J)毛细胞(HC)存活及噪声性听力损失(NIHL)中起重要作用。我们发现,内耳HC中缺乏Erk2的条件性敲除小鼠听力与对照小鼠相当,在正常条件下未出现HC损失。然而,我们发现这些敲除小鼠比对照小鼠更易受噪声影响,且从NIHL恢复的能力减弱。此外,与对照小鼠相比,我们观察到这些小鼠内毛细胞的存活率显著降低。我们的结果表明,ERK2在NIHL中HC的存活中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b76c/4649542/ca98e868e173/srep16839-f1.jpg

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