Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss

Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Her...

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Autores principales: He, Zu-Hong, Pan, Song, Zheng, Hong-Wei, Fang, Qiao-Jun, Hill, Kayla, Sha, Su-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994600/
https://www.ncbi.nlm.nih.gov/pubmed/33777956
http://dx.doi.org/10.3389/fcell.2021.648461
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author He, Zu-Hong
Pan, Song
Zheng, Hong-Wei
Fang, Qiao-Jun
Hill, Kayla
Sha, Su-Hua
author_facet He, Zu-Hong
Pan, Song
Zheng, Hong-Wei
Fang, Qiao-Jun
Hill, Kayla
Sha, Su-Hua
author_sort He, Zu-Hong
collection PubMed
description Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy.
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spelling pubmed-79946002021-03-27 Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss He, Zu-Hong Pan, Song Zheng, Hong-Wei Fang, Qiao-Jun Hill, Kayla Sha, Su-Hua Front Cell Dev Biol Cell and Developmental Biology Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy. Frontiers Media S.A. 2021-03-12 /pmc/articles/PMC7994600/ /pubmed/33777956 http://dx.doi.org/10.3389/fcell.2021.648461 Text en Copyright © 2021 He, Pan, Zheng, Fang, Hill and Sha. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
He, Zu-Hong
Pan, Song
Zheng, Hong-Wei
Fang, Qiao-Jun
Hill, Kayla
Sha, Su-Hua
Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
title Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
title_full Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
title_fullStr Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
title_full_unstemmed Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
title_short Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
title_sort treatment with calcineurin inhibitor fk506 attenuates noise-induced hearing loss
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994600/
https://www.ncbi.nlm.nih.gov/pubmed/33777956
http://dx.doi.org/10.3389/fcell.2021.648461
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