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

已知暴露于强烈的噪声会增加活性氧（ROS），并在耳蜗中引起氧化应激。还提出了ROS形成与听力损失之间的关系。激活蛋白-1（AP-1）是这些转录因子之一，已知会参与神经元死亡以及生存功能的压力诱导的凋亡。 AP-1与DMA上增强剂区域的共有核序列（TGAG/CTCA）与寡核苷酸结合，并调节其诱导靶靶标的转录。 AP-1由JUN家族蛋白（C-Jun，Jun B，Jun D）的同二聚体或JUN和FOS家族蛋白的异二聚体（C-FOS，FRA-1，FRA-2，FOS B）由ROS引起的各种类型的神经元细胞的压力，由ROS，NMDA和Kainic Acid APCHER，seiz和Transication和TransICE和Transication和Transiate和Transige and-iSCHEM，以及氨基酸受体引起的神经元细胞。最近，我们表明，声学创伤增强了耳蜗中AP-1的DNA结合，并且由于C-FOS蛋白的表达，它至少在PAR中。在这项研究中，噪声诱导的永久阈值移位（PTS）会导致耳蜗凋亡变化作为声学创伤模型。由于已知AP-1参与神经元细胞中的凋亡和存活反应，因此PTS模型显示了AP-1功能，Apoptsis和生存的两种可能性。 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. Westem印迹显示了包括血管的Corti和外侧壁的器官中的C-FOS表达，但在包括螺旋神经节细胞在内的耳蜗模拟物中没有。 Corti器官的免疫细胞化学仅在噪声暴露后才显示C-FOS表达。 C-FOS表达主要在耳蜗基底和第二圈的Hensen细胞和Deiter细胞中发现。由于阈值移位是暂时的，因此C-FOS的表达有望有助于Corti器官的生存或受保护功能。较少的