PMID- 12391593
OWN - NLM
STAT- MEDLINE
DCOM- 20021213
LR  - 20151119
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 70
IP  - 3
DP  - 2002 Nov 1
TI  - 4-Methylcatechol stimulates phosphorylation of Trk family neurotrophin receptors 
      and MAP kinases in cultured rat cortical neurons.
PG  - 335-9
AB  - Effects of 4-methycatechol (4MC), a potent stimulator of nerve growth factor and 
      brain-derived neurotrophic factor (BDNF) synthesis, on phosphorylation of 
      cellular molecules in cultured rat cortical neurons were examined. 4MC stimulated 
      tyrosine phosphorylation of various proteins of molecular weight from 10-300 kDa 
      including Trks, which are high-affinity neurotrophin receptors. Moreover, 4MC 
      enhanced the phosphorylation of serine 133 of mitogen-activated protein kinase 
      (MAPK/ERK) in a dose-dependent manner. Pretreatment of cultures with PD98059, a 
      selective inhibitor of MAPK kinase (MEK-1), inhibited 4MC-induced phosphorylation 
      of ERKs, demonstrating MEK-1-mediated activation. Therefore, it seems that 4MC 
      triggered the phosphorylation of Trks, resulting in the activation of the 
      subsequent MAPK/ERK signal cascade, or perhaps the involvement of BDNF action as 
      4MC can stimulate neuronal BDNF synthesis. The phosphorylation of MAPK/ERK was 
      unaffected, however, in the presence of cycloheximide, a protein synthesis 
      inhibitor, and K252a, a selective inhibitor of Trks, suggesting that the effect 
      of newly synthesized BDNF was negligible on this event, and that primary sites of 
      4MC actions are not limited only to Trks. These results suggest that 4MC 
      primarily activates multiple signal transduction molecules such as tyrosine 
      kinases, including Trks. A significant increase in the survival rate of cortical 
      neurons in the presence of 10 or 100 nM 4MC supported this idea, because the 
      concentrations were much lower than those for stimulation of BDNF synthesis. Our 
      results strongly suggest that the neurotrophic actions of 4MC found so far are 
      mediated predominantly by direct activation of some intracellular signals 
      including MAPK/ERK rather than by neurotrophin synthesis.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Sometani, Ayako
AU  - Sometani A
AD  - Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Nomoto, Hiroshi
AU  - Nomoto H
FAU - Nitta, Atsumi
AU  - Nitta A
FAU - Furukawa, Yoshiko
AU  - Furukawa Y
FAU - Furukawa, Shoei
AU  - Furukawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Catechols)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 12GLI7JGB3 (4-methylcatechol)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Aging/drug effects/*metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology/therapeutic use
MH  - Catechols/*pharmacology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/*metabolism/physiopathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Fetus
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Neurons/drug effects/*metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Pregnancy
MH  - Rats
MH  - Receptor, trkA/drug effects/metabolism
MH  - Receptor, trkB/drug effects/metabolism
MH  - Receptor, trkC/drug effects/metabolism
MH  - Receptors, Nerve Growth Factor/drug effects/*metabolism
EDAT- 2002/10/23 04:00
MHDA- 2002/12/17 04:00
CRDT- 2002/10/23 04:00
PHST- 2002/10/23 04:00 [pubmed]
PHST- 2002/12/17 04:00 [medline]
PHST- 2002/10/23 04:00 [entrez]
AID - 10.1002/jnr.10431 [doi]
PST - ppublish
SO  - J Neurosci Res. 2002 Nov 1;70(3):335-9. doi: 10.1002/jnr.10431.