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• W4285027415 endingPage "113280" @default.
• W4285027415 startingPage "113280" @default.
• W4285027415 abstract "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-induced 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 overexpressing SIRT3 may be a potential therapeutic approach for damaged IHC synapses induced by oxidative stress." @default.
• W4285027415 created "2022-07-12" @default.
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• W4285027415 date "2022-09-01" @default.
• W4285027415 modified "2023-10-01" @default.
• W4285027415 title "SIRT3-mediated deacetylation protects inner hair cell synapses in a H2O2-induced oxidative stress model in vitro" @default.
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• W4285027415 doi "https://doi.org/10.1016/j.yexcr.2022.113280" @default.
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