title: Sirt3 attenuates hydrogen peroxide-induced oxidative stress through the preservation of mitochondrial function in HT22 cells.
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 (H(2)O(2))-induced oxidative neuronal injury in HT22 mouse hippocampal cells. Treatment with H(2)O(2) 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 H(2)O(2)-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 H(2)O(2)-induced inhibition of mitochondrial complex activity and adenosine triphosphate (ATP) synthesis, the decrease in mitochondrial Ca(2+) 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 H(2)O(2), 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 H(2)O(2)-induced oxidative stress, possibly by inhibiting ROS accumulation and the activation of the mitochondrial apoptotic pathway.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The 101th Hospital of PLA, Rescue Center of Craniocerebral Injuries of PLA, Wuxi, Jiangsu 214044, P.R. China.
authors.forename: Yu-Hai
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The 101th Hospital of PLA, Rescue Center of Craniocerebral Injuries of PLA, Wuxi, Jiangsu 214044, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Rao
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yue-Fan
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006861:Hydrogen Peroxide / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D056566:Sirtuin 3 / Q000378:metabolism*
chemical_list: C525046:Sirt3 protein, mouse; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D056566:Sirtuin 3