| Project/Area Number |
15K07982
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Setsunan University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山口 太郎 摂南大学, 薬学部, 助教 (30710701)
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| Co-Investigator(Renkei-kenkyūsha) |
Ogita Kiyokazu 摂南大学, 薬学部, 教授 (90169219)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 感音難聴 / 音響外傷性難聴 / 細胞間コミュニケーション / 4HNE / パーオキシナイトライト / 一酸化窒素 / 聴覚機能 / カルパイン / 聴覚機能障害 / 難聴治療 |
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| Outline of Final Research Achievements |
There is evidence that the 4-hydroxynonenal (4-HNE)-adducted proteins increased in the cochlea during acoustic injury in the deafness model mouse. The purpose of this study was to elucidate the involvement of reactive oxygen species and its signal molecule in the mechanism underlying hearing loss, we evaluated auditory dysfunction following an intracoclear injection of 4-HNE. The auditory threshold markedly increased by 4-HNE. Additionally, a prior intracoclear injection of the calpain inhibitor significantly abolished this 4-HNE-induced hearing loss. Taken together, it was suggested that activation of calpain mediated by 4-HNE production may be involved at least in a part of the mechanism of sensorineural hearing loss. Therefore, it was expected that calpain activity due to lipid-peroxidation in the inner ear could become a novel drug discovery and/or treatment target in the treatment of sensory hearing loss.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性的な騒音性難聴や加齢性難聴といった感音性難聴は、主に内耳蝸牛内の障害によって起こる聴覚機能障害であり、その発症メカニズムについてはほとんど解明されていないため、有効な治療薬も存在しない。本研究では感音性難聴の新規治療において、内耳内での脂質過酸化によるカルパイン活性を抑制することが新たな創薬・治療ターゲットとなりうることが期待された。
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