Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress.
Yun Yeong LeeEun Sol GilIn Hye JeongHantai KimJeong Hun JangYun-Hoon ChoungPublished in: Cells (2021)
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.
Keyphrases
- heat shock
- induced apoptosis
- high frequency
- endoplasmic reticulum stress
- oxidative stress
- transcranial magnetic stimulation
- hearing loss
- heat shock protein
- heat stress
- cell cycle arrest
- cell death
- signaling pathway
- endoplasmic reticulum
- binding protein
- single cell
- cell proliferation
- living cells
- working memory
- transcription factor
- fluorescent probe
- small molecule
- stem cells
- quantum dots
- long non coding rna
- density functional theory
- stress induced