Treafment omcl prophylaxis of censommeural heaning loss by reguiating of transcription factor

通过调节转录因子治疗 omcl 预防耳廓听力损失

基本信息

批准号：
13671798
负责人：
OGAWA Kaoru
金额：
$ 2.3万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671798/
关键词：
sensorinenural pssaringle frascription factor temporary thresholol shift activator protein-1 oxpdaftve stress c-Fos HIF-1 音響外傷 C-FOS c-FOS

项目摘要

Exposure to intense noise has been known to increase the reactive oxygen species (ROS) and cause an oxidative stress in the cochlea. The relationship between the ROS formation and hearing loss has been also suggested. Activator protein-1 (AP-1) is one of these transcription factors and has been known to participate in stress-induced apoptosis in neuronal death and also in survival function. AP-1 binds to the oligonucleotides with a consensus core sequence (TGAG/CTCA) at an enhancer region on DMA and modulates transcription of its inducible target. AP-1 consists of homodimer of Jun family proteins (c-Jun, Jun B, Jun D) or heterodimer of Jun and Fos family proteins (c-Fos, Fra-1 , Fra-2, Fos B) Various types of stress to neuronal cells caused by ROS, amino acid receptors such as NMDA and kainic acid receptors, seizures, and transient brain ischemia are known to induce AP-1. Recently we have shown that acoustic trauma enhanced DNA binding of AP-1 in the cochlea, and it was at least in par … More t due to the expression of c-Fos protein. In this research, noise-induced permanent threshold shift (PTS) which causes apoptotic changes in the cochlea was used as an acoustic trauma model. Because AP-1 is known to participate in both of apoptotic and survival reactions in neuronal cells, therefore, the PTS model shows two possibilities of AP-1 functions, apopttsis and survival. In this resaerch, we employed noise-induced temporary threshold shift (TTS), which is known not to include apoptotic changes in order to elucidate the contribution of AP-1 for the survival of hair cellsGuinea pigs were exposed to 4kHz band noise of 110dB SPL for 1 to 5 hrand the expression of c-Fos was proved using the Western blotting analysis and immunocytchemistry. The Westem blotting showed c-Fos expression in the organ of Corti and lateral wall including the stria vascularis, but not in the cochlear modiolus including the spiral ganglion cells. Immunocytochemistry of the organ of Corti showed c-Fos expression only after the noise exposure. The c-Fos expression was mainly found in the Hensen cells and Deiter's cells of the basal and second turns of cochlea. As the threshold shift was temporary, the expression of c-Fos is supposed to contribute for the survival or protective functions of the organ of Corti. Less

众所周知，暴露在强烈的噪音中会增加活性氧 (ROS) 并导致耳蜗氧化应激。活性氧的形成与听力损失之间的关系也是如此。 AP-1 与这些转录因子的增强子区域的共有核心序列 (TGAG/CTCA) 结合，参与应激诱导的神经元死亡和存活功能。 AP-1 调节其诱导靶标的转录。 B) ROS、氨基酸受体（如 NMDA 和红藻氨酸受体）、癫痫发作和短暂性脑缺血引起的各种类型的神经细胞应激最近我们已经证明，声学信号会诱发 AP-1。创伤增强了耳蜗中 AP-1 的 DNA 结合，并且由于 c-Fos 蛋白的表达，这种作用至少增强了。在这项研究中，噪音诱导的永久阈值移位 (PTS) 会导致细胞凋亡变化。由于已知AP-1参与神经元细胞的凋亡和存活反应，因此，PTS模型显示AP-1功能的两种可能性：凋亡和存活。在研究中，我们采用了噪声诱导的临时阈值偏移 (TTS)，已知该阈值不包括细胞凋亡变化，以阐明 AP-1 对毛细胞存活的贡献将豚鼠暴露于 110dB SPL 的 4kHz 频带噪声下 1至5小时后，使用Westem印迹分析和免疫细胞化学证实c-Fos的表达。Westem印迹显示器官中c-Fos的表达。 Corti 器官和侧壁（包括血管纹）中，但在耳蜗蜗轴（包括螺旋神经节细胞）中，仅在噪声暴露后才显示 c-Fos 表达。c-Fos 表达主要在 Hensen 中发现。耳蜗基底和第二圈的细胞和 Deiter 细胞由于阈值变化是暂时的，因此 c-Fos 的表达应该有助于耳蜗的生存或保护功能。柯蒂氏器官。