D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice

BMC Molecular and Cell Biology

Research

Zhe Peng¹  Chunli Zhao¹  Zhengde Du¹  Shusheng Gong¹  Zijing Yang¹ 

[1]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, No.95, Yong’an Road, Xicheng District, 100050, Beijing, China

[2]Clinical Center for Hearing Loss, Capital Medical University, 100050, Beijing, China

关键词: Mitochondrial oxidative damage;    Apoptosis;    Stria vascularis;    D-galactose;    Mouse;   

DOI  :  10.1186/s12860-023-00480-7

 received in 2023-01-31, accepted in 2023-05-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAge-related hearing loss, known as presbycusis, is the result of auditory system degeneration. Numerous studies have suggested that reactive oxygen species (ROS) and mitochondrial oxidative damage play important roles in the occurrence and progression of aging. The D-galactose (D-gal)-induced aging model is well known and widely utilized in aging research. Our previous studies demonstrate that administration of D-gal causes mitochondrial oxidative damage and causes subsequent dysfunction in the cochlear ribbon synapses, which in turn leads to hearing changes and early stage presbycusis. Stria vascularis (SV) cells are vital for hearing function. However, it is unclear to what extent D-gal induces oxidative damage and apoptosis in the cochlear SV of mice. In addition, the source of the causative ROS in the cochlear SV has not been fully investigated.MethodsIn this study, we investigated ROS generation in the cochlear SV of mice treated with D-gal. Hearing function was measured using the auditory brainstem response (ABR). Immunofluorescence was used to examine apoptosis and oxidative damage. Transmission electron microscopy was also used to investigate the mitochondrial ultrastructure. DNA fragmentation was determined using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Mitochondrial membrane potential (MMP) and ATP were also measured.ResultsWe found that D-gal-treated mice exhibited a significant shift in the mean amplitude and latency of the ABR; a remarkable increase in the levels of NADPH oxidase (NOX-2), Uncoupling protein 2 (UCP2) and cleaved caspase-3 (c-Cas3) was observed, as well as an increase in the number of TUNEL-positive cells were observed in the SV of mice. Both the expression of the DNA oxidative damage biomarker 8-hydroxy-2-deoxyguanosine (8-OHdG) and a commonly occurring mitochondrial DNA deletion were markedly elevated in the SV of mice that had been treated with D-gal to induce aging. Conversely, the ATP level and MMP were significantly reduced in D-gal-induced aging mice. We also found alterations in the mitochondrial ultrastructure in the SV of aging mice, which include swollen and distorted mitochondrial shape, shortened and thickened microvilli, and the accumulation of lysosomes in the SV.ConclusionOur findings suggest that the impairment of cochlear SV during presbycusis may be caused by mitochondrial oxidative damage and subsequent apoptosis.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

12974_2023_2864_Article_IEq1.gif

Fig. 1

Fig. 1

Fig. 1

Fig. 6