Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-β-cyclodextrine is prestin-dependent

• Takahashi, Satoe

• Homma, Kazuaki

• Zhou, Yingjie

• Nishimura, Shinichi

• Duan, Chongwen

• Chen, Jessie

• Ahmad, Aisha

• Cheatham, Mary Ann

• Zheng, Jing

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.

収録刊行物

• Scientific Reports

  Scientific Reports 6 21973-, 2016-02-23

  Nature Publishing Group

キーワード

• Multidisciplinary

詳細情報

• CRID: 1050001335835666048
• NII論文ID: 120005818274
• ISSN: 20452322
• DOI: 10.1038/srep21973
• HANDLE: 2433/216012
• Web Site: https://www.nature.com/articles/srep21973.pdf
• Web Site: https://www.nature.com/articles/srep21973
• 本文言語コード: en
• 資料種別: journal article
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