PMID- 23841933
OWN - NLM
STAT- MEDLINE
DCOM- 20131119
LR  - 20211203
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 127
IP  - 1
DP  - 2013 Oct
TI  - AMP-activated protein kinase counteracts brain-derived neurotrophic 
      factor-induced mammalian target of rapamycin complex 1 signaling in neurons.
PG  - 66-77
LID - 10.1111/jnc.12362 [doi]
AB  - Growth factors and nutrients, such as amino acids and glucose, regulate mammalian 
      target of rapamycin complex 1 (mTORC1) signaling and subsequent translational 
      control in a coordinated manner. Brain-derived neurotrophic factor (BDNF), the 
      most prominent neurotrophic factor in the brain, activates mTORC1 and induces 
      phosphorylation of its target, p70S6 kinase (p70S6K), at Thr389 in neurons. BDNF 
      also increases mammalian target of rapamycin-dependent novel protein synthesis in 
      neurons. Here, we report that BDNF-induced p70S6K activation is dependent on 
      glucose, but not amino acids, sufficiency in cultured cortical neurons. 
      AMP-activated protein kinase (AMPK) is the molecular background to this specific 
      nutrient dependency. Activation of AMPK, which is induced by glucose deprivation, 
      treatment with pharmacological agents such as 2-deoxy-D-glucose, metformin, and 
      5-aminoimidazole-4-carboxamide ribonucleoside or forced expression of a 
      constitutively active AMPKalpha subunit, counteracts BDNF-induced phosphorylation of 
      p70S6K and enhanced protein synthesis in cortical neurons. These results indicate 
      that AMPK inhibits the effects of BDNF on mTORC1-mediated translation in neurons.
CI  - (c) 2013 International Society for Neurochemistry.
FAU - Ishizuka, Yuta
AU  - Ishizuka Y
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Niigata, Japan; Department of Neurobiology and Behavior, Gunma 
      University Graduate School of Medicine, Gunma, Japan.
FAU - Kakiya, Naomasa
AU  - Kakiya N
FAU - Witters, Lee A
AU  - Witters LA
FAU - Oshiro, Noriko
AU  - Oshiro N
FAU - Shirao, Tomoaki
AU  - Shirao T
FAU - Nawa, Hiroyuki
AU  - Nawa H
FAU - Takei, Nobuyuki
AU  - Takei N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130729
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Multiprotein Complexes)
RN  - 9100L32L2N (Metformin)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/*physiology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/drug effects/metabolism
MH  - Deoxyglucose/pharmacology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Electroporation
MH  - Fibroblasts/metabolism
MH  - Glucose/deficiency/physiology
MH  - Hypoglycemic Agents/pharmacology
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Metformin/pharmacology
MH  - Methionine/metabolism
MH  - Multiprotein Complexes/*physiology
MH  - Neurons/*drug effects
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*physiology
OTO - NOTNLM
OT  - AMPK
OT  - BDNF
OT  - mTOR
OT  - neuron
OT  - protein synthesis
OT  - translation
EDAT- 2013/07/12 06:00
MHDA- 2013/11/20 06:00
CRDT- 2013/07/12 06:00
PHST- 2013/06/07 00:00 [received]
PHST- 2013/07/04 00:00 [revised]
PHST- 2013/07/05 00:00 [accepted]
PHST- 2013/07/12 06:00 [entrez]
PHST- 2013/07/12 06:00 [pubmed]
PHST- 2013/11/20 06:00 [medline]
AID - 10.1111/jnc.12362 [doi]
PST - ppublish
SO  - J Neurochem. 2013 Oct;127(1):66-77. doi: 10.1111/jnc.12362. Epub 2013 Jul 29.