Propofol induces ERK-dependant expression of c-Fos and Egr-1 in neuronal cells.
This study explored the effects of propofol on c-Fos and Egr-1 in neuroblastoma (N2A) cells. We demonstrate that propofol induced the expression of c-Fos and Egr-1 within 30 and 60 min of exposure time. At 16.8 microM concentration, propofol induced a 6 and 2.5-fold expression of c-Fos and Egr-1, respectively. However, at concentrations above 100 microM, propofol failed to induce expression of c-Fos or Egr-1. Propofol-induced c-Fos and Egr-1 transcription was unaffected by bicuculline, a gamma-aminobutyric acid-A receptor antagonist, but was abolished by PD98059, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor. Our study shows that clinically relevant concentrations of propofol induce c-Fos and Egr-1 expression through an extracellular signal-regulated kinase mediated and gamma-aminobutyric acid-A independent pathway.
Department of Anesthesiology, New York Methodist Hospital, Brooklyn, New York, USA.
Srivatsan
S
Kidambi
Joel
J
Yarmush
Wayne
W
Fong
Sangeetha
S
Kamath
Joseph
J
Schianodicola
Yaakov
Y
Nahmias
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D016762:Genes, fos / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015742:Propofol / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D004791:Enzyme Inhibitors; D005419:Flavonoids; D018682:GABA Agents; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D001640:Bicuculline; D015742:Propofol