title: Sirtuin 1 activation enhances the PGC-1α/mitochondrial antioxidant system pathway in status epilepticus.
abstract: Sirtuin 1 (SIRT1) regulates numerous neuronal processes, including metabolism, antioxidation and aging, through activation of peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), an upstream regulator of mitochondrial biogenesis and function. However, the role of SIRT1 in the oxidative stress induced by seizures has yet to be elucidated. The present study aimed to investigate whether SIRT1 was involved in the activation of the PGC-1α/mitochondrial antioxidant system following status epilepticus (SE) in rats. The data demonstrated that SIRT1 expression and activity were enhanced in the rat hippocampus following SE. SIRT1 inhibition effectively blocked the SE-associated increase in PGC-1α and mitochondrial antioxidant enzymes, including superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Additionally, it was also demonstrated that the activation of SIRT1 enhanced mitochondrial electron transport chain complex I activity and increased ATP content. In conclusion, the present results suggest that SIRT1 activation may alleviate mitochondrial oxidative stress induced by seizures partially via PGC-1α signaling.
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiu-He
authors.initials: XH
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Jinan Central Hospital, Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Clinical Laboratory, People's Hospital of Shenzhen, Guangdong 518020, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Bo
authors.affiliation: Department of Neurology, Shandong Ankang Hospital, Jining, Shandong 272051, P.R. China.
authors.forename: Xian-Jin
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Zhao-Fu
authors.initials: ZF
authors.lastname: Chi
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004789:Enzyme Activation; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D056564:Sirtuin 1; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C501429:Ppargc1a protein, rat