Korean J Anesthesiol.
2012 Feb;62(2):166-171. 10.4097/kjae.2012.62.2.166.
Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in reactive oxygen species derived cellular injury
- Affiliations
-
- 1Department of Pharmacology, College of Medicine, Seonam University, Namwon, Korea.
- 2Department of Pathology, School of Medicine and Institute of Medical Science, Jeju National University, Jeju, Korea.
- 3Department of Chemical, Biological and Radiological Research, Korean Armed Forces Medical Research Institute, Daejeon, Korea.
- 4Department of Anesthesiology and Pain Medicine, College of Medicine, Konyang University, Daejeon, Korea. gangsi@kyuh.ac.kr
- 5Department of Parasitology, Catholic University of Daegu School of Medicine, Daegu, Korea.
- 6Department of Surgery, Seoul National University Hospital, Seoul, Korea.
- KMID: 2236297
- DOI: http://doi.org/10.4097/kjae.2012.62.2.166
Abstract
- 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 microg/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.
MeSH Terms
-
Acetylcholinesterase
Anoxia
Apoptosis
Blotting, Western
Cell Survival
Central Nervous System
Chromones
Flow Cytometry
Glucose Oxidase
Hemodynamics
Humans
Midazolam
Morpholines
Neuroblastoma
Neurons
Oxidative Stress
Reactive Oxygen Species
Soman
Acetylcholinesterase
Chromones
Glucose Oxidase
Midazolam
Morpholines
Reactive Oxygen Species
Soman
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