PMID- 24258317
OWN - NLM
STAT- MEDLINE
DCOM- 20150406
LR  - 20221207
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 53
IP  - 3
DP  - 2014 Jul
TI  - AChE and RACK1 promote the anti-inflammatory properties of fluoxetine.
PG  - 306-15
LID - 10.1007/s12031-013-0174-6 [doi]
AB  - Selective serotonin reuptake inhibitors (SSRIs) show anti-inflammatory effects, 
      suggesting a possible interaction with both Toll-like-receptor 4 (TLR4) responses 
      and cholinergic signaling through as yet unclear molecular mechanism(s). Our 
      results of structural modeling support the concept that the antidepressant 
      fluoxetine physically interacts with the TLR4-myeloid differentiation factor-2 
      complex at the same site as bacterial lipopolysaccharide (LPS). We also 
      demonstrate reduced LPS-induced pro-inflammatory interleukin-6 and tumor necrosis 
      factor alpha in human peripheral blood mononuclear cells preincubated with 
      fluoxetine. Furthermore, we show that fluoxetine intercepts the LPS-induced 
      decreases in intracellular acetylcholinesterase (AChE-S) and that AChE-S 
      interacts with the nuclear factor kappa B (NFkappaB)-activating intracellular 
      receptor for activated C kinase 1 (RACK1). This interaction may prevent NFkappaB 
      activation by residual RACK1 and its interacting protein kinase PKCbetaII. Our 
      findings attribute the anti-inflammatory properties of SSRI to surface membrane 
      interference with leukocyte TLR4 activation accompanied by intracellular 
      limitation of pathogen-inducible changes in AChE-S, RACK1, and PKCbetaII.
FAU - Waiskopf, Nir
AU  - Waiskopf N
AD  - Department of Biological Chemistry and The Institute of Chemistry, The Hebrew 
      University of Jerusalem, Jerusalem, 91904, Israel.
FAU - Ofek, Keren
AU  - Ofek K
FAU - Gilboa-Geffen, Adi
AU  - Gilboa-Geffen A
FAU - Bekenstein, Uriya
AU  - Bekenstein U
FAU - Bahat, Assaf
AU  - Bahat A
FAU - Bennett, Estelle R
AU  - Bennett ER
FAU - Podoly, Erez
AU  - Podoly E
FAU - Livnah, Oded
AU  - Livnah O
FAU - Hartmann, Gunther
AU  - Hartmann G
FAU - Soreq, Hermona
AU  - Soreq H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131121
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RACK1 protein, human)
RN  - 0 (Receptors for Activated C Kinase)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 01K63SUP8D (Fluoxetine)
RN  - EC 2.7.11.13 (Protein Kinase C beta)
RN  - EC 3.1.1.7 (ACHE protein, human)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Acetylcholinesterase/chemistry/*metabolism
MH  - Amino Acid Sequence
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Binding Sites
MH  - Fluoxetine/*pharmacology
MH  - GPI-Linked Proteins/chemistry/metabolism
MH  - GTP-Binding Proteins/chemistry/*metabolism
MH  - Humans
MH  - Interleukin-6/genetics/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Molecular Docking Simulation
MH  - Molecular Sequence Data
MH  - Monocytes/drug effects/metabolism
MH  - Neoplasm Proteins/chemistry/*metabolism
MH  - Protein Binding
MH  - Protein Kinase C beta/metabolism
MH  - Receptors for Activated C Kinase
MH  - Receptors, Cell Surface/chemistry/*metabolism
MH  - Selective Serotonin Reuptake Inhibitors/*pharmacology
MH  - Toll-Like Receptor 4/chemistry/metabolism
EDAT- 2013/11/22 06:00
MHDA- 2015/04/07 06:00
CRDT- 2013/11/22 06:00
PHST- 2013/09/10 00:00 [received]
PHST- 2013/11/05 00:00 [accepted]
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2015/04/07 06:00 [medline]
AID - 10.1007/s12031-013-0174-6 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2014 Jul;53(3):306-15. doi: 10.1007/s12031-013-0174-6. Epub 2013 
      Nov 21.