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タイトル: | Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-β-cyclodextrine is prestin-dependent |
著者: | Takahashi, Satoe Homma, Kazuaki Zhou, Yingjie Nishimura, Shinichi Duan, Chongwen Chen, Jessie Ahmad, Aisha Cheatham, Mary Ann Zheng, Jing |
著者名の別形: | 西村, 慎一 |
発行日: | 23-Feb-2016 |
出版者: | Nature Publishing Group |
誌名: | Scientific Reports |
巻: | 6 |
論文番号: | 21973 |
抄録: | Niemann-Pick type C1 disease (NPC1) is a fatal genetic disorder caused by impaired intracellular cholesterol trafficking. Recent studies reported ototoxicity of 2-hydroxypropyl- β-cyclodextrin (HPβCD), a cholesterol chelator and the only promising treatment for NPC1. Because outer hair cells (OHCs) are the only cochlear cells affected by HPβCD, we investigated whether prestin, an OHC-specific motor protein, might be involved. Single, high-dose administration of HPβCD resulted in OHC death in prestin wildtype (WT) mice whereas OHCs were largely spared in prestin knockout (KO) mice in the basal region, implicating prestin's involvement in ototoxicity of HPβCD. We found that prestin can interact with cholesterol in vitro, suggesting that HPβCD-induced ototoxicity may involve disruption of this interaction. Time-lapse analysis revealed that OHCs isolated from WT animals rapidly deteriorated upon HPβCD treatment while those from prestin-KOs tolerated the same regimen. These results suggest that a prestin-dependent mechanism contributes to HPβCD ototoxicity. |
著作権等: | © 2016, Nature Publishing Group. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/216012 |
DOI(出版社版): | 10.1038/srep21973 |
PubMed ID: | 26903308 |
出現コレクション: | 学術雑誌掲載論文等 |
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