Sirt3 attenuates hydrogen peroxide-induced oxidative stress through the preservation of mitochondrial function in HT22 cells

Dai,Shu-Hui; Chen,Tao; Wang,Yu-Hai; Zhu,Jie; Luo,Peng; Rao,Wei; Yang,Yue-Fan; Fei,Zhou; Jiang,Xiao-Fan

doi:10.3892/ijmm.2014.1876

Sirt3 attenuates hydrogen peroxide-induced oxidative stress through the preservation of mitochondrial function in HT22 cells

Authors:
- Shu-Hui Dai
- Tao Chen
- Yu-Hai Wang
- Jie Zhu
- Peng Luo
- Wei Rao
- Yue-Fan Yang
- Zhou Fei
- Xiao-Fan Jiang
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Affiliations: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Neurosurgery, The 101th Hospital of PLA, Rescue Center of Craniocerebral Injuries of PLA, Wuxi, Jiangsu 214044, P.R. China
Published online on: August 4, 2014 https://doi.org/10.3892/ijmm.2014.1876
Pages: 1159-1168

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Abstract

Sirtuins (Sirt) are a family of phylogenetically conserved nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylases, among which Sirt3 resides primarily in the mitochondria and serves as a stress responsive deacetylase, playing a role in protecting cells from damage under stress conditions. The present study aimed to investigate the role of Sirt3 in hydrogen peroxide (H2O2)-induced oxidative neuronal injury in HT22 mouse hippocampal cells. Treatment with H2O2 increased the expression of Sirt3 in a dose- and time-dependent manner, and the knockdown of Sirt3 using specific small interfering RNA (siRNA) exacerbated the H2O2-induced neuronal injury. The overexpression of Sirt3 induced by lentiviral transfection significantly reduced the generation of reactive oxygen species (ROS) and lipid peroxidation following injury, whereas the activities of endogenous antioxidant enzymes were not affected. Further experiments revealed that the H2O2-induced inhibition of mitochondrial complex activity and adenosine triphosphate (ATP) synthesis, the decrease in mitochondrial Ca2+ buffering capacity and mitochondrial swelling were all partly reversed by Sirt3. Furthermore, the overexpression of Sirt3 attenuated the release of cytochrome c, the increase in the Bax/Bcl-2 ratio, as well as caspase-9/caspase-3 activity induced by H2O2, and eventually inhibited apoptotic neuronal cell death. These results suggest that Sirt3 acts as a prosurvival factor, playing an essential role in protecting HT22 cells under H2O2-induced oxidative stress, possibly by inhibiting ROS accumulation and the activation of the mitochondrial apoptotic pathway.

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