2002 Fiscal Year Final Research Report Summary
Treafment omcl prophylaxis of censommeural heaning loss by reguiating of transcription factor
| Project/Area Number |
13671798
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Keio University |
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Principal Investigator |
OGAWA Kaoru Keio Univ, Otolaryngology Professor, 医学部, 教授 (00169179)
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| Co-Investigator(Kenkyū-buntansha) |
OGITA Kiyokazu Setsunan Univ, Pharmacology Assistant Professor, 薬学部, 助教授 (90169219)
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| Project Period (FY) |
2001 – 2002
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| Keywords | sensorinenural pssaringle / frascription factor / temporary thresholol shift / activator protein-1 / oxpdaftve stress / c-Fos / HIF-1 |
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| Research Abstract |
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
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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 cells
Guinea 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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[Publications] 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)
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