PMID- 17592535
OWN - NLM
STAT- MEDLINE
DCOM- 20070809
LR  - 20181113
IS  - 1673-7067 (Print)
IS  - 1995-8218 (Electronic)
IS  - 1995-8218 (Linking)
VI  - 23
IP  - 2
DP  - 2007 Mar
TI  - Inhibition of the MAPK/ERK cascade: a potential transcription-dependent mechanism 
      for the amnesic effect of anesthetic propofol.
PG  - 119-24
AB  - Intravenous anesthetics are known to cause amnesia, but the underlying molecular 
      mechanisms remain elusive. To identify a possible molecular mechanism, we 
      recently turned our attention to a key intracellular signaling pathway organized 
      by a family of mitogen-activated protein kinases (MAPKs). As a prominent 
      synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to 
      nuclear transcriptional events essential for the development and/or maintenance 
      of different forms of synaptic plasticity (long-term potentiation and long-term 
      depression) and memory formation. To define the role of MAPK-dependent 
      transcription in the amnesic property of anesthetics, we conducted a series of 
      studies to examine the effect of a prototype intravenous anesthetic propofol on 
      the MAPK response to N-methyl-D-aspartate receptor (NMDAR) stimulation in 
      hippocampal neurons. Our results suggest that propofol possesses the ability to 
      inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular 
      signal-regulated protein kinase 1/2 (ERK1/2). Concurrent inhibition of 
      transcriptional activity also occurs as a result of inhibited responses of ERK1/2 
      to NMDA. These findings provide first evidence for an inhibitory modulation of 
      the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to 
      elucidate a transcription-dependent mechanism processing the amnesic effect of 
      anesthetics.
FAU - Fibuch, Eugene E
AU  - Fibuch EE
AD  - Department of Anesthesiology, University of Missouri-Kansas City School of 
      Medicine, Saint Lukeos Hospital, Kansas City, Missouri 64108, USA.
FAU - Wang, John Q
AU  - Wang JQ
LA  - eng
GR  - R01-DA010355/DA/NIDA NIH HHS/United States
GR  - R01-MH061469/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Singapore
TA  - Neurosci Bull
JT  - Neuroscience bulletin
JID - 101256850
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Amnesia/chemically induced/enzymology
MH  - Anesthetics, Intravenous/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/*drug effects/metabolism
MH  - Hippocampus/cytology/drug effects/enzymology
MH  - Long-Term Potentiation/drug effects/physiology
MH  - Memory/drug effects/physiology
MH  - Mitogen-Activated Protein Kinase 1/drug effects
MH  - Mitogen-Activated Protein Kinase 3/drug effects
MH  - Neurons/*drug effects/enzymology
MH  - Propofol/*pharmacology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Transcriptional Activation/*drug effects
PMC - PMC5550596
EDAT- 2007/06/27 09:00
MHDA- 2007/08/10 09:00
PMCR- 2008/03/01
CRDT- 2007/06/27 09:00
PHST- 2007/06/27 09:00 [pubmed]
PHST- 2007/08/10 09:00 [medline]
PHST- 2007/06/27 09:00 [entrez]
PHST- 2008/03/01 00:00 [pmc-release]
AID - 17 [pii]
AID - 10.1007/s12264-007-0017-y [doi]
PST - ppublish
SO  - Neurosci Bull. 2007 Mar;23(2):119-24. doi: 10.1007/s12264-007-0017-y.