Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress

Zhibiao Liu; Bing Fei; Lisheng Xie; Jin Liu; Xiaorui Chen; Wenyan Zhu; Lingyun Lv; Wei Ma; Ziwen Gao; Jie Hou; Wandong She

doi:10.1515/biol-2021-0057

Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress

Open Life Sci. 2021 Jul 1;16(1):695-702. doi: 10.1515/biol-2021-0057. eCollection 2021.

Authors

Zhibiao Liu^{1

2}, Bing Fei³, Lisheng Xie¹, Jin Liu⁴, Xiaorui Chen⁴, Wenyan Zhu^{1

2}, Lingyun Lv^{1

2}, Wei Ma¹, Ziwen Gao¹, Jie Hou^{1

5}, Wandong She^{1

4

5}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing 210008, China.
² Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Nanjing, China.
³ Department of Otolaryngology-Head and Neck Surgery, Affiliated Huai'an Hospital of Xuzhou Medical University, 62 South Huaihai Road, Huai'an 223002, China.
⁴ Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China.
⁵ Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China.

Abstract

Background: To analyze mechanisms of action of glucocorticoid treatment for endoplasmic reticulum stress (ERS) in sensorineural hearing loss (SNHL), we aimed to evaluate the expression and activation status of the protein kinase RNA-like ER kinase (PERK)-C/EBP homologous protein (CHOP) pathway, which is the major pathway in the ERS.

Methods: In the present study, we established an in vitro ERS model using tunicamycin-treated hair-cell-like HEI-OC1 cells. The effect of dexamethasone on proliferation inhibition, apoptosis, and ATF4-CHOP pathway in HEI-OC1 cells was examined by CCK-8 assay, flow cytometry, western blotting, and reverse transcription PCR, respectively.

Results: In HEI-OC1 cells, dexamethasone was shown to significantly reduce the tunicamycin-induced expression of ATF4 and CHOP in the context of sustained viability and proliferation, a therapeutic effect that was reversible by co-treatment with a glucocorticoid antagonist.

Conclusion: Dexamethasone can protect hair-cell-like HEI-OC1 cells from ERS damage, which may be one of the mechanisms of action for GCs in SNHL treatment.

Keywords: PERK–CHOP pathway; dexamethasone; endoplasmic reticulum stress; mifepristone.