D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice
Abstract Background Age-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...
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| Format: | Article |
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BMC
2023-08-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-023-00480-7 |
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| author | Zhe Peng Chunli Zhao Zijing Yang Shusheng Gong Zhengde Du |
| author_facet | Zhe Peng Chunli Zhao Zijing Yang Shusheng Gong Zhengde Du |
| author_sort | Zhe Peng |
| collection | DOAJ |
| description | Abstract Background Age-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. Methods In 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. Results We 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. Conclusion Our findings suggest that the impairment of cochlear SV during presbycusis may be caused by mitochondrial oxidative damage and subsequent apoptosis. |
| first_indexed | 2024-03-10T16:52:10Z |
| format | Article |
| id | doaj.art-bb5d6dec0e5f452387b65bdd3f3d960c |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-03-10T16:52:10Z |
| publishDate | 2023-08-01 |
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| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-bb5d6dec0e5f452387b65bdd3f3d960c2023-11-20T11:16:02ZengBMCBMC Molecular and Cell Biology2661-88502023-08-0124111010.1186/s12860-023-00480-7D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of miceZhe Peng0Chunli Zhao1Zijing Yang2Shusheng Gong3Zhengde Du4Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical UniversityAbstract Background Age-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. Methods In 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. Results We 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. Conclusion Our findings suggest that the impairment of cochlear SV during presbycusis may be caused by mitochondrial oxidative damage and subsequent apoptosis.https://doi.org/10.1186/s12860-023-00480-7Mitochondrial oxidative damageApoptosisStria vascularisD-galactoseMouse |
| spellingShingle | Zhe Peng Chunli Zhao Zijing Yang Shusheng Gong Zhengde Du D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice BMC Molecular and Cell Biology Mitochondrial oxidative damage Apoptosis Stria vascularis D-galactose Mouse |
| title | D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice |
| title_full | D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice |
| title_fullStr | D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice |
| title_full_unstemmed | D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice |
| title_short | D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice |
| title_sort | d galactose induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice |
| topic | Mitochondrial oxidative damage Apoptosis Stria vascularis D-galactose Mouse |
| url | https://doi.org/10.1186/s12860-023-00480-7 |
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