OSBPL2 inhibition leads to apoptosis of cochlea hair cells in age-related hearing loss by inhibiting the AKT/FOXG1 signaling pathway.

Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE

Original Publication: Albany, NY : Impact Journals, LLC

Apoptosis*/drug effects ; Proto-Oncogene Proteins c-akt*/metabolism ; Signal Transduction*/drug effects ; Hydrogen Peroxide*/pharmacology ; Hydrogen Peroxide*/toxicity ; Hair Cells, Auditory*/metabolism ; Hair Cells, Auditory*/drug effects ; Hair Cells, Auditory*/pathology ; Forkhead Transcription Factors*/metabolism ; Forkhead Transcription Factors*/genetics; Animals ; Mice ; Nerve Tissue Proteins/metabolism ; Nerve Tissue Proteins/genetics ; Presbycusis/metabolism ; Presbycusis/pathology ; Presbycusis/genetics ; Cell Line ; Aging/metabolism ; Mice, Inbred C57BL ; Acetates ; Benzopyrans ; Heterocyclic Compounds, 3-Ring

Age-related hearing loss (AHL) is a prevalent and multifaceted condition that significantly impacts a substantial portion of the aging population. Oxysterol Binding Protein-like 2 (OSBPL2) has been identified as a causal gene for hearing loss. However, its role in AHL is still unclear. In this study, we investigated the effect of OSBPL2 on the survival of cochlea hair cells. To simulate AHL in vitro , hair cell-like inner ear cells (HEI-OC1) were exposed to H 2 O 2 treatment. OSBPL2 expression was significantly increased in HEI-OC1 cells after H 2 O 2 treatment. OSBPL2 knockdown augmented cell death and apoptosis in H 2 O 2 -induced HEI-OC1 cells. Besides, H 2 O 2 treatment also led to the inactivation of the AKT and FOXG1 signaling pathways in HEI-OC1 cells. Mechanistically, OSBPL2 silencing reinforced the inactivation of the FOXG1 signaling pathway in H 2 O 2 -treated HEI-OC1 cells by inhibiting the AKT signaling pathway. Under H 2 O 2 treatment, AKT inhibition by MK2206 augmented the apoptosis of HEI-OC1 cells; on the contrary, AKT activation by SC79 treatment partially rescued the apoptosis of OSBPL2-knockdown HEI-OC1 cells. In addition, FOXG1 silencing significantly reversed the effects of AKT activation on OSBPL2-knockdown HEI-OC1 cells. Moreover, OSBPL2 expression and the activation status of the AKT/FOXG1 signaling pathway were confirmed in the cochleae of young and old C57BL/6 mice. In conclusion, our study provides evidence that OSBPL2 inhibition sensitizes HEI-OC1 cells to H 2 O 2 -induced apoptosis via inactivation of the AKT/FOXG1 signaling pathway, suggesting that OSBPL2 acts as an important regulator in AHL.

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Keywords: AKT; FOXG1; OSBPL2; age-related hearing loss; cochlea hair cells

EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
BBX060AN9V (Hydrogen Peroxide)
0 (Forkhead Transcription Factors)
0 (Foxg1 protein, mouse)
0 (Nerve Tissue Proteins)
0 (MK 2206)
0 (AKT activator SC79)
0 (Acetates)
0 (Benzopyrans)
0 (Heterocyclic Compounds, 3-Ring)

Date Created: 20241030 Date Completed: 20241106 Latest Revision: 20241113

20241113

PMC11552636

10.18632/aging.206138

39475791