Open Access

ARTICLE

Bhlhe40 protects cochlear hair cell-like HEI-OC1 cells against HO‑triggered oxidative injury

LITING WEN^#, XIAOXIA ZENG^#, PEIXIONG CHEN, DAPENG ZHAO, YANGYANG LI, XIANHAI ZENG^*

Department of Otorhinolaryngology, Longgang Otorhinolaryngology Hospital and Shenzhen Key Laboratory of Otorhinolaryngology, Shenzhen Institute of Otorhinolaryngology, Shenzhen, China

* Corresponding Author: XIANHAI ZENG. Email:

BIOCELL 2024, 48(6), 991-999. https://doi.org/10.32604/biocell.2024.050219

Received 31 January 2024; Accepted 21 March 2024; Issue published 10 June 2024

Abstract

Background: Cochlear hair cell injury is a common pathological feature of hearing loss. The basic helix-loop-helix family, member e40 (Bhlhe40), a gene belonging to the basic helix-loop-helix (bHLH) family, exhibits strong transcriptional repression activity. Methods: Oxidative damage, in House Ear Institute-Organ of Corti 1 (HEI‑OC1) cells, was caused using hydrogen peroxide (HO). The Ad-Bhlhe40 particles were constructed to overexpress Bhlhe40 in HEI-OC1 cells. Various assays including cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay (TUNEL), flow cytometry, immunofluorescence, and corresponding commercial kits were employed to investigate the impacts of Bhlhe40 on cell viability, apoptosis, oxidative stress levels, mitochondrial membrane potential and cellular senescence. Additionally, a dual-luciferase reporter assay was performed to confirm the targeting of the histone deacetylases 2 (Hdac2) by Bhlhe40. Results: The results revealed that Bhlhe40 was downregulated in HO‑treated HEI‑OC1 cells, but its overexpression improved cell viability and mitigated HO‑induced oxidative injury in HEI‑OC1 cells with increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and decrease of reactive oxygen species (ROS) levels. Besides, overexpression of Bhlhe40 suppressed HO‑triggered cell senescence, as evidenced by the fact that the upregulation of P53, P21, and P16 in HEI-OC1 cells treated with HO were all alleviated by Bhlhe40 overexpression. And we further verified that overexpression of Bhlhe40 could inhibit the expression of Hdac2, which may be related to the repression of Hdac2 transcription. Conclusion: This study suggests that Bhlhe40 plays a protective role against senescence and oxidative damage in cochlear hair cells exposed to HO.

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