title: Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity.
abstract: Sevoflurane, one of the most commonly used volatile anesthetics in clinical treatment, has been shown to induce a widespread increase in brain apoptosis. However, the underlying mechanism is still unknown. Sestrin 2 has been recently shown to regulate intracellular reactive oxygen species (ROS) levels and play a crucial role in p53-dependent antioxidant defenses. In this study, our results indicated that administration of Sevoflurane elevated the gene and protein expression of Sestrin-2 in a dose dependent manner in human neuroblastoma M17 cells. It was shown that silence of Sestrin-2 by small RNA interference (siRNA) ominously exacerbated the increase in intracellular ROS and reduction of SOD activity induced by Sevoflurane treatment. Notably, knockdown of Sestrin-2 in M17 cells significantly increases the number of apoptotic cells after treatment with Sevoflurane. Mechanistically, we also found that Sevoflurane treatment resulted in a reduced amount of the cytosolic anti-apoptotic protein Bcl-2 but an increased amount of Bax, which was exacerbated by knockdown of Sestrin-2. In addition, knockdown of Sestrin-2 remarkably increased the elevated cleaved Caspase-3 expression. Finally, we showed that the induction of Sestrin-2 by Sevoflurane was mediated by p53. These results suggest that the suppressive effects of Sestrin-2 on neuroapoptosis against the Sevoflurane anesthesia in neuronal cells might be associated with modulation of mitochondrial pathway.
authors.affiliation: Department of Anesthesia, Qilu Hospital of Shandong University, 107 Wenhua West Road, Jinan, 250012, China, wenboyi223@yeah.net.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yi
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Guo
authors.forename: Dongliang
authors.initials: D
authors.lastname: Li
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008738:Methyl Ethers / Q000633:toxicity*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077149:Sevoflurane; D000084622:Sestrins
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D000077149:Sevoflurane; C465398:SESN2 protein, human; D000084622:Sestrins