Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling.
Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling.
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DOI：
10.4103/1463-1741.144418
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发表时间：
2014-11
期刊：
影响因子：
0.7
通讯作者：
Davis RR
中科院分区：
文献类型：
--
作者：
Alagramam KN;Stepanyan R;Jamesdaniel S;Chen DH;Davis RR
噪声性听力损失(NIHL)是世界范围内的重大公共卫生问题。揭示与NIHL相关的早期分子事件将揭示导致听力损失的机制。我们的目的是研究不同水平的噪声暴露后的即时分子反应，并确定介导NIHL的共同和不同的途径。以前的工作表明，暴露于116分贝声压级(DBSPL)宽带噪声1h的小鼠比暴露于110dBSPL宽带噪声的小鼠有更大的阈值漂移，因此我们在本研究中使用了这两种噪声水平。将4-8周龄CBA/CAJ小鼠暴露于无噪声(对照组)或宽带噪声1h，然后对噪声暴露后即刻提取的耳蜗总RNA进行转录组分析。在所有数据集中都发现了以前发现的和新的基因。暴露于116dBSPL噪声后，最早的反应包括243个基因上调和61个基因下调，而类似的110dBSPL噪声暴露使155个基因上调和221个基因下调。生物信息学分析表明，丝裂原活化蛋白激酶(MAPK)信号通路在两种水平的噪声暴露中都是主要途径。然而，暴露于不同的噪声水平后，一些MAPK信号基因在质量和数量上都存在差异。与钙信号相关的Cacna 1b、Cacna 1g和Pla2g6在110dBSPL暴露后表达下调，而Fos表达的增加倍数低于116dBSPL暴露后的水平。这些微妙的变化提供了对可能导致NIHL差异的因素的洞察，尽管共同的途径被激活。
Noise-induced hearing loss (NIHL) is a major public health issue worldwide. Uncovering the early molecular events associated with NIHL would reveal mechanisms leading to the hearing loss. Our aim is to investigate the immediate molecular responses after different levels of noise exposure and identify the common and distinct pathways that mediate NIHL. Previous work showed mice exposed to 116 decibels sound pressure level (dB SPL) broadband noise for 1 h had greater threshold shifts than the mice exposed to 110 dB SPL broadband noise, hence we used these two noise levels in this study. Groups of 4–8-week-old CBA/CaJ mice were exposed to no noise (control) or to broadband noise for 1 h, followed by transcriptome analysis of total cochlear RNA isolated immediately after noise exposure. Previously identified and novel genes were found in all data sets. Following exposure to noise at 116 dB SPL, the earliest responses included up-regulation of 243 genes and down-regulation of 61 genes, while a similar exposure at 110 dB SPL up-regulated 155 genes and down-regulated 221 genes. Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the major pathway in both levels of noise exposure. Nevertheless, both qualitative and quantitative differences were noticed in some MAPK signaling genes, after exposure to different noise levels. Cacna1b, Cacna1g, and Pla2g6, related to calcium signaling were down-regulated after 110 dB SPL exposure, while the fold increase in the expression of Fos was relatively lower than what was observed after 116 dB SPL exposure. These subtle variations provide insight on the factors that may contribute to the differences in NIHL despite the activation of a common pathway.