Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress
Presbycusis, or age-related hearing loss, is a prevalent disease that severely affects the physical and mental health of the elderly. Oxidative stress and mitochondrial (mt)DNA deletion mutation are considered as major factors in the pathophysiology of age-related hearing loss. The 4977-bp deletion...
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2020-02-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/4353 |
| _version_ | 1797260871188086784 |
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| author | Jun Li Xiang Dai Xuelian He Rong Yang Zhongfang Xia Han Xiao |
| author_facet | Jun Li Xiang Dai Xuelian He Rong Yang Zhongfang Xia Han Xiao |
| author_sort | Jun Li |
| collection | DOAJ |
| description |
Presbycusis, or age-related hearing loss, is a prevalent disease that severely affects the physical and mental health of the elderly. Oxidative stress and mitochondrial (mt)DNA deletion mutation are considered as major factors in the pathophysiology of age-related hearing loss. The 4977-bp deletion in human mtDNA (common deletion, corresponding to the 4834-bp mtDNA deletion in rats) is suggested to be closely associated with the pathogenesis of age-related hearing loss. Superoxide dismutase 2 (SOD2), an isoform of SOD that is exclusively expressed in the intracellular mitochondrial matrix, plays a crucial role in oxidative resistance against mitochondrial superoxide. Previous research has shown that methylation of the promoter region of the SOD2 gene decreased the expression of SOD2 in marginal cells (MCs) extracted from the inner ear of rats subjected to D-galactose-induced mtDNA4834 deletion. However, the relationship between SOD2 methylation and mtDNA4834 deletion under oxidative stress remains to be elucidated. Herein, an oxidative damage model was established in the extracted MCs using hydrogen peroxide (H2O2), which increased the methylation level of SOD2 and the copy number of mtDNA4834 mutation in MCs. Decreasing the methylation level of SOD2 using 5-azacytidine, a DNA methylation inhibitor, reduced oxidative stress and the copy number of mtDNA4834 mutation and inhibited H2O2-induced apoptosis. The present work demonstrates that decreasing the methylation of SOD2 suppresses the mtDNA4834 deletion in MCs under oxidative stress and provides potential insights to the intervention therapy of aging-related hearing loss.
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| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:32:12Z |
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| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
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| series | Biomolecules & Biomedicine |
| spelling | doaj.art-26b0530b26bd4f399f5795fb4a092a6a2024-03-15T14:30:06ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2020-02-0120110.17305/bjbms.2019.4353Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stressJun Li0Xiang Dai1https://orcid.org/0000-0002-7908-9831Xuelian He2Rong Yang3https://orcid.org/0000-0003-0265-8888Zhongfang Xia4Han Xiao5https://orcid.org/0000-0001-5655-0173Department of Otorhinolaryngology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaLaboratory of Reproduction, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCentral Laboratory, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Health, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Otorhinolaryngology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBiological Sample Bank, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Presbycusis, or age-related hearing loss, is a prevalent disease that severely affects the physical and mental health of the elderly. Oxidative stress and mitochondrial (mt)DNA deletion mutation are considered as major factors in the pathophysiology of age-related hearing loss. The 4977-bp deletion in human mtDNA (common deletion, corresponding to the 4834-bp mtDNA deletion in rats) is suggested to be closely associated with the pathogenesis of age-related hearing loss. Superoxide dismutase 2 (SOD2), an isoform of SOD that is exclusively expressed in the intracellular mitochondrial matrix, plays a crucial role in oxidative resistance against mitochondrial superoxide. Previous research has shown that methylation of the promoter region of the SOD2 gene decreased the expression of SOD2 in marginal cells (MCs) extracted from the inner ear of rats subjected to D-galactose-induced mtDNA4834 deletion. However, the relationship between SOD2 methylation and mtDNA4834 deletion under oxidative stress remains to be elucidated. Herein, an oxidative damage model was established in the extracted MCs using hydrogen peroxide (H2O2), which increased the methylation level of SOD2 and the copy number of mtDNA4834 mutation in MCs. Decreasing the methylation level of SOD2 using 5-azacytidine, a DNA methylation inhibitor, reduced oxidative stress and the copy number of mtDNA4834 mutation and inhibited H2O2-induced apoptosis. The present work demonstrates that decreasing the methylation of SOD2 suppresses the mtDNA4834 deletion in MCs under oxidative stress and provides potential insights to the intervention therapy of aging-related hearing loss. https://www.bjbms.org/ojs/index.php/bjbms/article/view/4353Oxidative stresssuperoxide dismutase 2SOD2methylationmtDNA4834 deletionage-related hearing loss |
| spellingShingle | Jun Li Xiang Dai Xuelian He Rong Yang Zhongfang Xia Han Xiao Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress Biomolecules & Biomedicine Oxidative stress superoxide dismutase 2 SOD2 methylation mtDNA4834 deletion age-related hearing loss |
| title | Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress |
| title_full | Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress |
| title_fullStr | Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress |
| title_full_unstemmed | Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress |
| title_short | Effect of SOD2 methylation on mitochondrial DNA4834-bp deletion mutation in marginal cells under oxidative stress |
| title_sort | effect of sod2 methylation on mitochondrial dna4834 bp deletion mutation in marginal cells under oxidative stress |
| topic | Oxidative stress superoxide dismutase 2 SOD2 methylation mtDNA4834 deletion age-related hearing loss |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/4353 |
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