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KMID : 0356920120620020166
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Korean Journal of Anesthesiology
2012 Volume.62 No. 2 p.166 ~ p.171
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Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury
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Chong Won-Seog
Hyun Chang-Lim
Park Min-Kyu
Park Jeong-Min
Song Hyun-Ouk
Park Tae-Jin
Lim Young-Su
Cho Choon-Kyu
Kang Po-Soon
Kwon Hee-Uk
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Abstract
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Background: Soman, a potent irreversible acetylcholinesterase (AChE) inhibitor, induces delayed neuronal injury by reactive oxygen species (ROS). Midazolam is used in patients with pathologic effects of oxidative stresses such as infection, hemodynamic instability and hypoxia. We investigated whether midazolam protects the Central Nervous System (CNS) from soman intoxication. The present study was performed to determine whether midazolam protects B35 cells from ROS stress for the purpose of exploring an application of midazolam to soman intoxication.
Methods: Glucose oxidase (GOX) induced ROS stress was used in a B35 neuroblastoma cell model of ROS induced neuronal injury. To investigate the effect of midazolam on cell viability, LDH assays and fluorescence activated cell sorting (FACS) analysis was performed. Western blotting was used for evaluating whether Akt-phosphorylation is involved in cell-protective effects of midazolam.
Results: GOX derived ROS injury decreased cell viability about 1.6-2 times compared to control; midazolam treatment (5 and 10 μg/ml) dose-dependently increased cell viability during ROS injury. On western blots, Akt-phosphorylation was induced during pretreatment with midazolam; it was diminished during co-treatment with LY-294002, an inhibitor of Akt-phosphorylation. FACS analysis confirmed that the cell protective effect of midazolam is mediated by an anti-apoptotic effect. GOX-induced apoptosis was inhibited by midazolam and the finding was diminished by LY-294002.
Conclusions: Midazolam protects neuronal cells from GOX-induced ROS injury; this effect is mediated by an anti-apoptotic effect through Akt-phosphorylation. This shows that midazolam may be useful in soman intoxication.
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KEYWORD
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Akt-phosphorylation, Midazolam, Reactive oxygen species (ROS), Soman
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