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SIRT3-mediated deacetylation protects inner hair cell synapses in a H2O2-induced oxidative stress model in vitro

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收录情况： ◇ SCIE

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单位： [1]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China [2]Clinical Center for Hearing Loss, Capital Medical University, Beijing, 100050, China

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Oxidative stress is considered a driving event in the damage to inner hair cell (IHC) synapses. Mitochondrial deacetylase Sirtuin 3 (SIRT3) is an important regulator of reactive oxygen species (ROS) production. However, the effect of SIRT3 on IHC synapses remains elusive. In this study, we treated cochlear basilar membrane (CBM) with hydrogen peroxide (H2O2) to establish an oxidative stress model in vitro. The H2O2-induced CBM exhibited decreased the number of IHC synapses with low levels of ATP and mitochondrial membrane potential. Additionally, H2O2-incuded CBM showed markedly reduced levels of forkhead box protein O 3a (FOXO3a), superoxide dismutase 2 (SOD2), and isocitrate dehydrogenase 2 (IDH2), thereby increasing ROS generation. SIRT3 overexpression via administrating nicotinamide riboside in the H2O2-induced CBM protected IHC synapses against oxidative stress and inhibited hair cell apoptosis. We further demonstrated that SIRT3 overexpression led to upregulation of IDH2, and hypoacetylation of several proteins, such as FOXO3a and SOD2, which in turn reduced the levels of ROS and improved mitochondrial function. Collectively, these findings reveal that SIRT3 may be a potential therapeutic approach for damaged IHC synapses induced by oxidative stress.Copyright © 2022. Published by Elsevier Inc.

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出版当年[2021]版：

大类 | 3 区医学

小类 | 4 区肿瘤学 4 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

JCR分区：

出版当年[2020]版：

Q3 CELL BIOLOGY Q3 ONCOLOGY

最新[2023]版：

Q2 ONCOLOGY Q3 CELL BIOLOGY

影响因子： 最新[2023版] 3.3 最新五年平均[2021-2025] 3.3 出版当年[2020版] 3.905 出版当年五年平均[2016-2020] 4.121 出版前一年[2019版] 3.383 出版后一年[2021版] 4.145

第一作者：

第一作者单位： [1]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China [2]Clinical Center for Hearing Loss, Capital Medical University, Beijing, 100050, China

通讯作者：

通讯机构： [1]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China [2]Clinical Center for Hearing Loss, Capital Medical University, Beijing, 100050, China [*1]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. [*2]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, No.95, Yong’an Road, Xicheng District, Beijing 100050, China.

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