Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury
BackgroundSoman, 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...
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Korean Society of Anesthesiologists
2012-02-01
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| Series: | Korean Journal of Anesthesiology |
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| Online Access: | http://ekja.org/upload/pdf/kjae-62-166.pdf |
| _version_ | 1818316615497809920 |
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| author | Won Seog Chong Chang Lim Hyun Min Kyu Park Jeong Min Park Hyun-Ouk Song Taejin Park Young Su Lim Choon Kyu Cho Po Soon Kang Hee Uk Kwon |
| author_facet | Won Seog Chong Chang Lim Hyun Min Kyu Park Jeong Min Park Hyun-Ouk Song Taejin Park Young Su Lim Choon Kyu Cho Po Soon Kang Hee Uk Kwon |
| author_sort | Won Seog Chong |
| collection | DOAJ |
| description | BackgroundSoman, 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.MethodsGlucose 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.ResultsGOX 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.ConclusionsMidazolam 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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| issn | 2005-6419 2005-7563 |
| language | English |
| last_indexed | 2024-12-13T09:24:15Z |
| publishDate | 2012-02-01 |
| publisher | Korean Society of Anesthesiologists |
| record_format | Article |
| series | Korean Journal of Anesthesiology |
| spelling | doaj.art-bac57493abe64315974468134837cb152022-12-21T23:52:40ZengKorean Society of AnesthesiologistsKorean Journal of Anesthesiology2005-64192005-75632012-02-0162216617110.4097/kjae.2012.62.2.1667275Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injuryWon Seog Chong0Chang Lim Hyun1Min Kyu Park2Jeong Min Park3Hyun-Ouk Song4Taejin Park5Young Su Lim6Choon Kyu Cho7Po Soon Kang8Hee Uk Kwon9Department of Pharmacology, College of Medicine, Seonam University, Namwon, Korea.Department of Pathology, School of Medicine and Institute of Medical Science, Jeju National University, Jeju, Korea.Department of Chemical, Biological and Radiological Research, Korean Armed Forces Medical Research Institute, Daejeon, Korea.Department of Anesthesiology and Pain Medicine, College of Medicine, Konyang University, Daejeon, Korea.Department of Parasitology, Catholic University of Daegu School of Medicine, Daegu, Korea.Department of Surgery, Seoul National University Hospital, Seoul, Korea.Department of Anesthesiology and Pain Medicine, College of Medicine, Konyang University, Daejeon, Korea.Department of Anesthesiology and Pain Medicine, College of Medicine, Konyang University, Daejeon, Korea.Department of Anesthesiology and Pain Medicine, College of Medicine, Konyang University, Daejeon, Korea.Department of Anesthesiology and Pain Medicine, College of Medicine, Konyang University, Daejeon, Korea.BackgroundSoman, 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.MethodsGlucose 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.ResultsGOX 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.ConclusionsMidazolam 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.http://ekja.org/upload/pdf/kjae-62-166.pdfakt-phosphorylationmidazolamreactive oxygen species (ros)soman |
| spellingShingle | Won Seog Chong Chang Lim Hyun Min Kyu Park Jeong Min Park Hyun-Ouk Song Taejin Park Young Su Lim Choon Kyu Cho Po Soon Kang Hee Uk Kwon Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury Korean Journal of Anesthesiology akt-phosphorylation midazolam reactive oxygen species (ros) soman |
| title | Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury |
| title_full | Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury |
| title_fullStr | Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury |
| title_full_unstemmed | Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury |
| title_short | Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury |
| title_sort | midazolam protects b35 neuroblastoma cells through akt phosphorylation in reactive oxygen species derived cellular injury |
| topic | akt-phosphorylation midazolam reactive oxygen species (ros) soman |
| url | http://ekja.org/upload/pdf/kjae-62-166.pdf |
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