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低剂量雷帕霉素诱导耳蜗外沟细胞自噬。

Low-dose rapamycin-induced autophagy in cochlear outer sulcus cells.

作者信息

Saegusa Chika, Hosoya Makoto, Nishiyama Takanori, Saeki Tsubasa, Fujimoto Chisato, Okano Hideyuki, Fujioka Masato, Ogawa Kaoru

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery Keio University School of Medicine Tokyo Japan.

Department of Physiology Keio University School of Medicine Tokyo Japan.

出版信息

Laryngoscope Investig Otolaryngol. 2020 May 29;5(3):520-528. doi: 10.1002/lio2.392. eCollection 2020 Jun.

DOI:10.1002/lio2.392
PMID:32596496
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7314457/
Abstract

OBJECTIVES

Autophagy is an intracellular housekeeping process that degrades cytoplasmic organelles, damaged molecules, and abnormal proteins or pathogens and is essential for normal hearing. Recent studies revealed the essential roles of autophagy in hearing and balance. The aim of this study was to evaluate the activation state of rapamycin-induced autophagy in cochlear outer sulcus cells (OSCs).

METHODS

We used autophagy reporter transgenic mice expressing the green fluorescent protein-microtubule-associated protein light chain 3 (GFP-LC3) fusion protein and counted GFP-LC3 puncta in cochlear OSCs to evaluate the activation state of autophagy after oral administration of rapamycin.

RESULTS

We observed basal level GFP-LC3 expression and an increase in the number of GFP-LC3 puncta in cochlear OSCs by oral administration of rapamycin. This increase was detected when the daily rapamycin intake was as low as 0.025 mg/kg, and it was dose dependent. The increased number of puncta was more at the basal turn than the apical turn.

CONCLUSION

Oral intake of low-dose rapamycin activates autophagy in cochlear OSCs.

LEVEL OF EVIDENCE

NA.

摘要

目的

自噬是一种细胞内的清理过程,可降解细胞质细胞器、受损分子、异常蛋白质或病原体,对正常听力至关重要。最近的研究揭示了自噬在听力和平衡中的重要作用。本研究的目的是评估雷帕霉素诱导的耳蜗外沟细胞(OSCs)自噬的激活状态。

方法

我们使用表达绿色荧光蛋白-微管相关蛋白轻链3(GFP-LC3)融合蛋白的自噬报告基因转基因小鼠,通过计数耳蜗OSCs中的GFP-LC3斑点来评估口服雷帕霉素后自噬的激活状态。

结果

我们观察到耳蜗OSCs中基础水平的GFP-LC3表达,并且口服雷帕霉素后GFP-LC3斑点数量增加。当雷帕霉素的每日摄入量低至0.025 mg/kg时即可检测到这种增加,且呈剂量依赖性。斑点数量增加在蜗底比蜗顶更多。

结论

口服低剂量雷帕霉素可激活耳蜗OSCs中的自噬。

证据水平

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/1b193f1ab85e/LIO2-5-520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/acc6fb691be0/LIO2-5-520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/fc546a5d64b3/LIO2-5-520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/30bf7b2462fb/LIO2-5-520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/a8293d88e95f/LIO2-5-520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/949af24a7946/LIO2-5-520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/1b193f1ab85e/LIO2-5-520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/acc6fb691be0/LIO2-5-520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/fc546a5d64b3/LIO2-5-520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/30bf7b2462fb/LIO2-5-520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/a8293d88e95f/LIO2-5-520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/949af24a7946/LIO2-5-520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95ce/7314457/1b193f1ab85e/LIO2-5-520-g006.jpg

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