Cho Younsook, Gong Tzy-Wen L, Kanicki Ariane, Altschuler Richard A, Lomax Margaret I
Department of Cell and Developmental Biology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Brain Res Mol Brain Res. 2004 Nov 4;130(1-2):134-48. doi: 10.1016/j.molbrainres.2004.07.017.
In mammals, exposure to intense noise produces a permanent hearing loss called permanent threshold shift (PTS), whereas a moderate noise produces only a temporary threshold shift (TTS). Little is known about the molecular responses to such high intensity noise exposures. In this study we used gene arrays to examine the early response to acoustic overstimulation in the rat cochlea. We compared cochlear RNA from noise-exposed rats with RNA from unexposed controls. The intense PTS noise induced several immediate early genes encoding both transcription factors (c-FOS, EGR1, NUR77/TR3) and cytokines (PC3/BTG2, LIF and IP10). In contrast, the TTS noise down-regulated the gene for growth hormone. The response of these genes to different noise intensities was examined by quantitative RT-PCR 2.5 h after the 90-min noise exposure. For most genes, the extent of induction correlates with the intensity of the noise exposure. Three proteins (EGR1, NUR77/TR3, and IP10) were detected in many regions of the unexposed cochlea. After exposure to 120 dB noise, these proteins were present at higher levels or showed extended expression in additional regions of the cochlea. LIF was undetectable in the cochlea of unexposed rats, but could be seen in the organ of Corti and spiral ganglion neurons following noise. NUR77/TR3 was a nuclear protein before noise, but following noise translocated to the cytoplasm. These studies provide new insights into the molecular response to noise overstimulation in the mammalian cochlea.
在哺乳动物中，暴露于高强度噪声会导致一种称为永久性阈移（PTS）的永久性听力损失，而中等强度噪声只会产生暂时性阈移（TTS）。对于这种高强度噪声暴露的分子反应知之甚少。在本研究中，我们使用基因芯片来检测大鼠耳蜗对声学过度刺激的早期反应。我们将噪声暴露大鼠的耳蜗RNA与未暴露对照组的RNA进行了比较。高强度的PTS噪声诱导了几个立即早期基因，这些基因编码转录因子（c-FOS、EGR1、NUR77/TR3）和细胞因子（PC3/BTG2、LIF和IP10）。相比之下，TTS噪声下调了生长激素基因。在90分钟噪声暴露后2.5小时，通过定量RT-PCR检测了这些基因对不同噪声强度的反应。对于大多数基因，诱导程度与噪声暴露强度相关。在未暴露的耳蜗的许多区域检测到三种蛋白质（EGR1、NUR77/TR3和IP10）。暴露于120 dB噪声后，这些蛋白质在耳蜗的其他区域以更高水平存在或显示出表达扩展。LIF在未暴露大鼠的耳蜗中未检测到，但在噪声后可在柯蒂氏器和螺旋神经节神经元中看到。NUR77/TR3在噪声前是一种核蛋白，但噪声后易位到细胞质中。这些研究为哺乳动物耳蜗对噪声过度刺激的分子反应提供了新的见解。
