title: Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis.
abstract: Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. fmmudaishuhui@163.com.
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 710032, China. fmmuchentao@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, the 101th Hospital of People's Liberation Army, Rescue Center of Craniocerebral Injuries of PLA, Wuxi 214044, China. wuxi101wyh@163.com.
authors.forename: Yu-Hai
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the 101th Hospital of People's Liberation Army, Rescue Center of Craniocerebral Injuries of PLA, Wuxi 214044, China. wuxi101zhuj@163.com.
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 710032, China. fmmuluopeng@163.com.
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 710032, China. fmmuraowei@126.com.
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 710032, China. fmmuyangyf@163.com.
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 710032, China. fmmuzhoufei@163.com.
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 710032, China. fmmujiangxiaofan@163.com.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004272:DNA, Mitochondrial; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D056566:Sirtuin 3; D002118:Calcium