DUSP1 Protects Against D-galactose-induced HEI-OC1 Cell Injury by Promoting Mitophagy-associated Changes
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Updated: Nov 6, 2026

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Published on: May 26, 2023
1Department of Otorhinolaryngology, Head and Neck Surgery, Xi'an International Medical Center Hospital, Xi'an 710100, Shaanxi, China.
Introduction:
Dual-Specificity Phosphatase 1 (DUSP1) has been proven to be closely correlated with Age-Related Hearing Loss (ARHL) and mitophagy progression. However, the function of DUSP1 in cochlear hair cell injury and the underlying mechanism remain to be elucidated.
Methods:
In this study, we employed D-galactose (D-gal)- induced mouse models and D-gal-treated HEI-OC1 cells to simulate the ARHL process. Auditory brainstem response (ABR) detection was performed to evaluate mouse hearing function. Immunohistochemistry and immunofluorescence were utilized to assess DUSP1 expression levels. Cell senescence and apoptosis were quantified through senescence-associated β-galactosidase (SA-β-gal) activity and TUNEL assay, respectively. Mitochondrial function was assessed by measuring mitochondrial membrane potential and ATP levels. Mitophagy-associated changes were evaluated using Transmission Electron Microscopy (TEM) and immunofluorescence colocalization of LCB and MitoTracker.
Results:
D-gal administration resulted in a significant deterioration in hearing function, accompanied by increased SA-β-gal activity, reduced the number of hair cells in basal turns of the cochlear basilar membranes, and decreased DUSP1 expression. Overexpression of DUSP1 mitigated D-gal-induced senescence and apoptosis in HEIOC1 cells, leading to enhanced mitochondrial membrane potential and ATP levels, and increased mitophagy-associated changes. Conversely, knockdown of BNIP3L/NIX partially reversed the protective effects of DUSP1 by inhibiting mitophagy-associated changes and promoting cellular senescence and apoptosis.
Discussion:
Our findings highlighted the critical role of DUSP1‑driven mitophagyassociated changes against D‑gal‑triggered cochlear hair cell damage. Modulation of the DUSP1‑BNIP3L/NIX axis might offer new therapeutic insights for ARHL intervention.
Conclusion:
The in vitro experimental results demonstrated that DUSP1 alleviated Dgal- induced cochlear hair cell injury via positively regulating mitophagy-associated changes. BNIP3L/NIX partially mediated the protective effects of DUSP1 in HEI-OC1 cells.
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