Cargando…

Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress

Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Yun Yeong, Gil, Eun Sol, Jeong, In Hye, Kim, Hantai, Jang, Jeong Hun, Choung, Yun-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468389/
https://www.ncbi.nlm.nih.gov/pubmed/34572102
http://dx.doi.org/10.3390/cells10092454
_version_ 1784573655210000384
author Lee, Yun Yeong
Gil, Eun Sol
Jeong, In Hye
Kim, Hantai
Jang, Jeong Hun
Choung, Yun-Hoon
author_facet Lee, Yun Yeong
Gil, Eun Sol
Jeong, In Hye
Kim, Hantai
Jang, Jeong Hun
Choung, Yun-Hoon
author_sort Lee, Yun Yeong
collection PubMed
description Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role of HSF1 in ARHL. In this study, we demonstrated that the loss of inner and outer hair cells and their supporting cells was predominant in the high-frequency region (basal turn, 32 kHz) in ARHL cochleae. In the aging cochlea, levels of the ER stress marker proteins p-eIF2α and CHOP increased as HSF1 protein levels decreased. The levels of various heat shock proteins (HSPs) also decreased, including HSP70 and HSP40, which were markedly downregulated, and the expression levels of Bax and cleaved caspase-3 apoptosis-related proteins were increased. However, HSF1 overexpression showed significant hearing protection effects in the high-frequency region (basal turn, 32 kHz) by decreasing CHOP and cleaved caspase-3 and increasing the HSP40 and HSP70 proteins. These findings were confirmed by HSF1 functional studies using an auditory cell model. Therefore, we propose that HSF1 can function as a mediator to prevent ARHL by decreasing ER stress-dependent apoptosis in the aging cochlea.
format Online
Article
Text
id pubmed-8468389
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84683892021-09-27 Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress Lee, Yun Yeong Gil, Eun Sol Jeong, In Hye Kim, Hantai Jang, Jeong Hun Choung, Yun-Hoon Cells Article Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role of HSF1 in ARHL. In this study, we demonstrated that the loss of inner and outer hair cells and their supporting cells was predominant in the high-frequency region (basal turn, 32 kHz) in ARHL cochleae. In the aging cochlea, levels of the ER stress marker proteins p-eIF2α and CHOP increased as HSF1 protein levels decreased. The levels of various heat shock proteins (HSPs) also decreased, including HSP70 and HSP40, which were markedly downregulated, and the expression levels of Bax and cleaved caspase-3 apoptosis-related proteins were increased. However, HSF1 overexpression showed significant hearing protection effects in the high-frequency region (basal turn, 32 kHz) by decreasing CHOP and cleaved caspase-3 and increasing the HSP40 and HSP70 proteins. These findings were confirmed by HSF1 functional studies using an auditory cell model. Therefore, we propose that HSF1 can function as a mediator to prevent ARHL by decreasing ER stress-dependent apoptosis in the aging cochlea. MDPI 2021-09-17 /pmc/articles/PMC8468389/ /pubmed/34572102 http://dx.doi.org/10.3390/cells10092454 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Yun Yeong
Gil, Eun Sol
Jeong, In Hye
Kim, Hantai
Jang, Jeong Hun
Choung, Yun-Hoon
Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress
title Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress
title_full Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress
title_fullStr Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress
title_full_unstemmed Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress
title_short Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress
title_sort heat shock factor 1 prevents age-related hearing loss by decreasing endoplasmic reticulum stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468389/
https://www.ncbi.nlm.nih.gov/pubmed/34572102
http://dx.doi.org/10.3390/cells10092454
work_keys_str_mv AT leeyunyeong heatshockfactor1preventsagerelatedhearinglossbydecreasingendoplasmicreticulumstress
AT gileunsol heatshockfactor1preventsagerelatedhearinglossbydecreasingendoplasmicreticulumstress
AT jeonginhye heatshockfactor1preventsagerelatedhearinglossbydecreasingendoplasmicreticulumstress
AT kimhantai heatshockfactor1preventsagerelatedhearinglossbydecreasingendoplasmicreticulumstress
AT jangjeonghun heatshockfactor1preventsagerelatedhearinglossbydecreasingendoplasmicreticulumstress
AT choungyunhoon heatshockfactor1preventsagerelatedhearinglossbydecreasingendoplasmicreticulumstress