Leupeptin, a Calpain Inhibitor, Protects Inner Ear Hair Cells from Aminoglycoside Ototoxicity
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- Momiyama Junko
- Department of Otorhinolaryngology, Hirosaki University School of Medicine
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- Hashimoto Toshimitsu
- Department of Otorhinolaryngology, Hirosaki University School of Medicine
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- Matsubara Atsushi
- Department of Otorhinolaryngology, Hirosaki University School of Medicine
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- Futai Kazunori
- Department of Otorhinolaryngology, Hirosaki University School of Medicine
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- Namba Atsushi
- Department of Otorhinolaryngology, Hirosaki University School of Medicine
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- Shinkawa Hideichi
- Department of Otorhinolaryngology, Hirosaki University School of Medicine
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抄録
Inner ear hair cells play a major role in the auditory pathway that converts sound stimulation into electrical signals, and then into a neural code. However this function is often lost by aminoglycoside ototoxicity. The injury of inner ear hair cells from aminoglycoside treatment is considered apoptosis, and caspase is an important participant in the apoptosis pathway in many organs. It has been reported that calpain, a calcium-dependent protease, is essential for mediation and promotion of cell death. The purpose of the present study was to investigate effects of caspase and calpain inhibitors on the inner ear hair cells after aminoglycoside treatment, and to explore the cell death pathway. Cochlea explant cultures were prepared from mice of postnatal 6 days, cultured with neomycin and/or protease inhibitors, and then stained with phalloidin-fluorescein isothiocyanate (phalloidin-FITC), which was used as a marker to identify surviving hair cells. We demonstrated that neomycin (0.1-1 mM) reduced the number of outer hair cells in a dose-dependent manner. Furthermore, we showed that leupeptin, a calpain inhibitor, significantly protects against the neomycin-induced loss of outer hair cells, whereas a caspase inhibitor was effective only against a lower concentration of neomycin (0.2 mM). Using the TdT-mediated dUTP-biotin nick and labeling method, we also found that a calpain inhibitor, but not a caspase inhibitor, prevents apoptotic DNA fragmentation after treatment with 1 mM neomycin. These results suggest that calpain, rather than caspase, may be responsible for apoptosis induced by aminoglycoside. Thus, leupeptin may prevent hearing loss from aminoglycoside ototoxity.
収録刊行物
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 209 (2), 89-97, 2006
東北ジャーナル刊行会
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詳細情報
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- CRID
- 1390001204240454656
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- NII論文ID
- 10017492952
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- NII書誌ID
- AA00863920
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- ISSN
- 13493329
- 00408727
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- 本文言語コード
- en
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- データソース種別
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- JaLC
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- 抄録ライセンスフラグ
- 使用不可