Korean J Anesthesiol.  2008 Feb;54(2):189-196. 10.4097/kjae.2008.54.2.189.

Propofol-induced Immediate Early Gene Expression in Human Neuroblastoma Cell Lines

• Kim DI
• Kim JR
• Kim SY

• KMID: 2244022
• DOI: http://doi.org/10.4097/kjae.2008.54.2.189

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.

Keyword

cyclin; immediate early gene; propofol; signal transduction

MeSH Terms

Anesthetics, General
Anesthetics, Intravenous
Blotting, Western
Cell Cycle
Cell Cycle Proteins
Cell Line
Cell Survival
Cyclin A
Cyclin B1
Cyclins
Flavonoids
Gene Expression
Genes, Immediate-Early
Humans
Neuroblastoma
NF-kappa B
Phosphorylation
Phosphotransferases
Proliferating Cell Nuclear Antigen
Propofol
Signal Transduction
Anesthetics, General
Anesthetics, Intravenous
Cell Cycle Proteins
Cyclin A
Cyclin B1
Cyclins
Flavonoids
NF-kappa B
Phosphotransferases
Proliferating Cell Nuclear Antigen
Propofol