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Korean J Anesthesiol > Volume 54(2); 2008 > Article
Korean Journal of Anesthesiology 2008;54(2):189-196.
DOI: https://doi.org/10.4097/kjae.2008.54.2.189   
Propofol-induced Immediate Early Gene Expression in Human Neuroblastoma Cell Lines.
Dong Il Kim, Jae Ryong Kim, Seong Yong Kim
1Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea. seongyong@med.yu.ac.kr
2Department of Anesthesiology and Pain Medicine, Masan Bokeum Hospital, Masan, Korea.
Abstract
BACKGROUND
General anesthetics were known to induce expression of immediate early genes (IEGs), including c-fos and c-jun. However, mechanisms of IEG induction by general anesthetics were not fully understood.
METHODS
IEG induction by propofol, a kind of intravenous anesthetics, and signal transduction pathways for propofol-induced IEG expression were investigated in human neuroblastoma cell line IMR32 and CHP134 with Northern and Western blot analysis.
RESULTS
Cell viability was significantly decreased in IMR32 and CHP134 treated with increasing concentrations of propofol. IMR32 was more sensitive to propofol-induced cytotoxicity than CHP134. Propofol did not affect the cell cycle profile of IMR32. Expression of cyclin A, cyclin B1, CDK4 and CDK6 was increased in IMR32 by propofol treatment in a time-dependent manner. However, expression of cyclin A and CDK4 was decreased in CHP134. Proliferating cell nuclear antigen (PCNA) was increased in both IMR32 and CHP134 treated with propofol from 6 h to 24 h. c-fos and c-jun were induced by propofol treatment in both cells. Propofol also induced extracellular signal-regulated kinase (ERK) phosphorylation in both cells. Pretreatment of PD98059, an MEK inhibitor, blocked propofol-induced c-fos and c-jun expression.Propofol treatment was decreased nuclear transcription factor-kappa B (NF-kappa B) expression in IMR32, but not in CHP134.
CONCLUSIONS
Propofol-induced c-fos expression might be mediated through ERK phosphorylation in both IMR32 and CHP134. Propofol-induced cytotoxicity, changes in expressions of cell cycle regulatory proteins, expression of IEGs, ERK phosphorylation, and NF-kappa B expression were different between IMR32 and CHP134.
Key Words: cyclin; immediate early gene; propofol; signal transduction
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