Treafment omcl prophylaxis of censommeural heaning loss by reguiating of transcription factor
Treafment omcl prophylaxis of censommeural heaning loss by reguiating of transcription factor
批准号:
13671798
负责人:
OGAWA Kaoru
金额:
$2.3万
依托单位:
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
项目状态:
已结题
起止时间:
2001 至 2002
中文摘要
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英文摘要
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
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Ogawa,K, Takei,S, Inoue,Y, Kanzak,J.: "Effect of PGEI on idiopathic sudden sensorineural hearing loss:a double-blind study."Otol Neurotol. 23. 665-668 (2002)
Okawa,K、Takei,S、Inoue,Y、Kanzak,J.:“PGEI 对特发性突发感音神经性听力损失的影响:双盲研究。”Otol Neurotol。
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通讯作者:
Ogita,K, Okuda,H, Kitano,M, Fujinami,Y, Ozaki,K, Yoneda,Y.: "Localization of activator protein-1 complex with DNA binding activity in mitochondria of murine brain after in vivo treatment with kainate"J Neurosci. 22. 2561-2570 (2002)
Ogita,K, Okuda,H, Kitano,M, Fujinami,Y, Ozaki,K, Yoneda,Y.:“红藻氨酸体内处理后,具有 DNA 结合活性的激活蛋白 1 复合物在小鼠大脑线粒体中的定位”J
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Ogita K, Okuda H et al.: "Lu vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons"J Neurochem. 85. 1336-1346 (2003)
Ogita K、Okuda H 等人:“NMDA 受体对小鼠海马锥体神经元中红藻氨酸诱导的兴奋性毒性的体内神经保护作用”J Neurochem。
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作者:
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通讯作者:
Ogawa K, Takei S et al.: "Effect of PGE1 on idiopathic sudden sensorineural hearig loss : a double-blind study"Otol Neurotol. 23. 665-668 (2002)
Okawa K、Takei S 等人:“PGE1 对特发性突发感音神经性听力损失的影响:双盲研究”Otol Neurotol。
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通讯作者:
Kanzaki,S, Ogawa,K, Camper,SA, Raphael,Y: "Transgene expression neonatal mouse inner ear explants mediated by first and advanced generation adebovirus vectors"Hear Res. 169. 112-120 (2002)
Kanzaki,S,Okawa,K,Camper,SA,Raphael,Y:“第一代和先进的腺病毒载体介导的转基因表达新生小鼠内耳外植体”Hear Res。
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