Low-dose Rapamycin-induced Autophagy in Cochlear Outer Sulcus Cells

Overview

Journal Laryngoscope Investig Otolaryngol

Publisher Wiley

Specialty Otorhinolaryngology

Date 2020 Jun 30

PMID 32596496

Citations 4

Authors

Chika Saegusa

Makoto Hosoya

Takanori Nishiyama

Tsubasa Saeki

Chisato Fujimoto

Hideyuki Okano

Masato Fujioka

Kaoru Ogawa

Affiliations

Soon will be listed here.

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.

Citing Articles

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Cellular autophagy, the compelling roles in hearing function and dysfunction.

Wan H, Zhang Y, Hua Q Front Cell Neurosci. 2022; 16:966202.

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Programmed cell death pathways in hearing loss: A review of apoptosis, autophagy and programmed necrosis.

Wu J, Ye J, Kong W, Zhang S, Zheng Y Cell Prolif. 2020; 53(11):e12915.

PMID: 33047870 PMC: 7653260. DOI: 10.1111/cpr.12915.

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

Saegusa C, Hosoya M, Nishiyama T, Saeki T, Fujimoto C, Okano H Laryngoscope Investig Otolaryngol. 2020; 5(3):520-528.

PMID: 32596496 PMC: 7314457. DOI: 10.1002/lio2.392.

References

Schulte B, Schmiedt R . Lateral wall Na,K-ATPase and endocochlear potentials decline with age in quiet-reared gerbils. Hear Res. 1992; 61(1-2):35-46. DOI: 10.1016/0378-5955(92)90034-k. View

Yoshino T, Sato E, Nakashima T, Nagashima W, Teranishi M, Nakayama A . The immunohistochemical analysis of pendrin in the mouse inner ear. Hear Res. 2004; 195(1-2):9-16. DOI: 10.1016/j.heares.2004.05.005. View

Lautermann J, ten Cate W, Altenhoff P, Grummer R, Traub O, Frank H . Expression of the gap-junction connexins 26 and 30 in the rat cochlea. Cell Tissue Res. 1998; 294(3):415-20. DOI: 10.1007/s004410051192. View

Xia A, Ikeda K, Katori Y, Oshima T, Kikuchi T, Takasaka T . Expression of connexin 31 in the developing mouse cochlea. Neuroreport. 2000; 11(11):2449-53. DOI: 10.1097/00001756-200008030-00022. View

Saegusa C, Hosoya M, Nishiyama T, Saeki T, Fujimoto C, Okano H . Low-dose rapamycin-induced autophagy in cochlear outer sulcus cells. Laryngoscope Investig Otolaryngol. 2020; 5(3):520-528. PMC: 7314457. DOI: 10.1002/lio2.392. View

Ghavami S, Shojaei S, Yeganeh B, Ande S, Jangamreddy J, Mehrpour M . Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol. 2013; 112:24-49. DOI: 10.1016/j.pneurobio.2013.10.004. View

Benjamin D, Colombi M, Moroni C, Hall M . Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov. 2011; 10(11):868-80. DOI: 10.1038/nrd3531. View

Saeki T, Hosoya M, Shibata S, Okano H, Fujioka M, Ogawa K . Distribution of tight junctions in the primate cochlear lateral wall. Neurosci Lett. 2019; 717:134686. DOI: 10.1016/j.neulet.2019.134686. View

Ye B, Fan C, Shen Y, Wang Q, Hu H, Xiang M . The Antioxidative Role of Autophagy in Hearing Loss. Front Neurosci. 2019; 12:1010. PMC: 6333736. DOI: 10.3389/fnins.2018.01010. View

10.

Choi B, Kim H, Ito T, Lee K, Li X, Monahan K . Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition. J Clin Invest. 2011; 121(11):4516-25. PMC: 3204851. DOI: 10.1172/JCI59353. View

11.

Fang B, Xiao H . Rapamycin alleviates cisplatin-induced ototoxicity in vivo. Biochem Biophys Res Commun. 2014; 448(4):443-7. DOI: 10.1016/j.bbrc.2014.04.123. View

12.

Fujioka M, Akiyama T, Hosoya M, Kikuchi K, Fujiki Y, Saito Y . A phase I/IIa double blind single institute trial of low dose sirolimus for Pendred syndrome/DFNB4. Medicine (Baltimore). 2020; 99(19):e19763. PMC: 7220392. DOI: 10.1097/MD.0000000000019763. View

13.

Fujimoto C, Iwasaki S, Urata S, Morishita H, Sakamaki Y, Fujioka M . Autophagy is essential for hearing in mice. Cell Death Dis. 2017; 8(5):e2780. PMC: 5520715. DOI: 10.1038/cddis.2017.194. View

14.

Sehgal S . Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998; 31(5):335-40. DOI: 10.1016/s0009-9120(98)00045-9. View

15.

He Z, Guo L, Shu Y, Fang Q, Zhou H, Liu Y . Autophagy protects auditory hair cells against neomycin-induced damage. Autophagy. 2017; 13(11):1884-1904. PMC: 5788479. DOI: 10.1080/15548627.2017.1359449. View

16.

Nixon R . The role of autophagy in neurodegenerative disease. Nat Med. 2013; 19(8):983-97. DOI: 10.1038/nm.3232. View

17.

de Iriarte Rodriguez R, Pulido S, Rodriguez-de la Rosa L, Magarinos M, Varela-Nieto I . Age-regulated function of autophagy in the mouse inner ear. Hear Res. 2015; 330(Pt A):39-50. DOI: 10.1016/j.heares.2015.07.020. View

18.

Magarinos M, Pulido S, Aburto M, de Iriarte Rodriguez R, Varela-Nieto I . Autophagy in the Vertebrate Inner Ear. Front Cell Dev Biol. 2017; 5:56. PMC: 5445191. DOI: 10.3389/fcell.2017.00056. View

19.

Marino G, Fernandez A, Cabrera S, Lundberg Y, Cabanillas R, Rodriguez F . Autophagy is essential for mouse sense of balance. J Clin Invest. 2010; 120(7):2331-44. PMC: 2898610. DOI: 10.1172/JCI42601. View

20.

Ichimiya I, Suzuki M, MOGI G . Age-related changes in the murine cochlear lateral wall. Hear Res. 1999; 139(1-2):116-22. DOI: 10.1016/s0378-5955(99)00170-7. View