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The potential dual effects of sevoflurane on AKT/ GSK3β signaling pathway

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单位： [a]Department of Anesthesia,Critical Care and Pain Medicine, Geriatric Anesthesia Research Unit, Harvard Medical School, 149 13th St., Charlestown, MA 02129-2060, United States [b]Department of Anesthesiology, Tongji University, East Hospital, Shanghai, 200120, China [c]Research Center for Translational Medicine, School of Medicine, East Hospital, Shanghai, 200120, China [d]Department of Anesthesiology, Huazhong University of Science and Technology, Tongji Hospital, Wuhan, China

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关键词： AKT/GSK3β signaling pathway Anesthetic Phosphorylation Sevoflurane

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Background: Anesthesia with multiple exposures of commonly used inhalation anesthetic sevoflurane induces neuroinflammation and cognitive impairment in young mice, but anesthesia with a single exposure to sevoflurane does not. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway is involved in neurotoxicity and neurobehavioral deficits. However, whether sevoflurane can induce a dual effect (increase versus decrease) on the activation of AKT/GSK3β signaling pathway remains to be determined. We therefore set out to assess the effects of sevoflurane on AKT/GSK3β signaling pathway in vivo and in vitro. Methods: Six day-old wild-type mice were exposed to 3% sevoflurane two hours daily for one or three days. In the in vitro studies, H4 human neuroglioma cells were treated with 4% sevoflurane for two or six hours. We then determined the effects of different sevoflurane treatments on the levels of phosphorylated (P)-GSK3β(ser9) and P-AKT(ser473) by using Western blot analysis. Results: Here we show that anesthesia with 3% sevoflurane two hours daily for one day increased the levels of P-GSK3β(ser9) and P-AKT(ser473), but the anesthesia with 3% sevoflurane daily for three days decreased them in the mice. The treatment with 4% sevoflurane for two hours increased, but the treatment with 4% sevoflurane for six hours decreased, the levels of P-GSK3β(ser9) and P-AKT(ser473) in the H4 human neuroglioma cells. Conclusions: Anesthetic sevoflurane might induce a dual effect (increase versus decrease) on the activation of the AKT/GSK3β signaling pathway. These studies have established a system to perform further studies to determine the effects of sevoflurane on brain function. © 2014 Zhang et al.

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大类 | 3 区医学

小类 | 3 区医学：研究与实验

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第一作者单位： [a]Department of Anesthesia,Critical Care and Pain Medicine, Geriatric Anesthesia Research Unit, Harvard Medical School, 149 13th St., Charlestown, MA 02129-2060, United States [b]Department of Anesthesiology, Tongji University, East Hospital, Shanghai, 200120, China [c]Research Center for Translational Medicine, School of Medicine, East Hospital, Shanghai, 200120, China

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