PMID- 24604717
OWN - NLM
STAT- MEDLINE
DCOM- 20140925
LR  - 20211203
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 229
IP  - 11
DP  - 2014 Nov
TI  - IGF-1 alleviates NMDA-induced excitotoxicity in cultured hippocampal neurons 
      against autophagy via the NR2B/PI3K-AKT-mTOR pathway.
PG  - 1618-29
LID - 10.1002/jcp.24607 [doi]
AB  - Insulin-like growth factor-1 (IGF-1) is a brain-specific multifunctional protein 
      involved in neuronal polarity and axonal guidance. Mature IGF-1 triggers three 
      enzymes, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase 
      (PI3K), and phosphoinositide phospholipase C-gamma (PLC-gamma), which are its predominant 
      downstream regulators. The PI3K-AKT signaling pathway is upstream of the 
      mammalian target of rapamycin (mTOR), which is of great importance in the 
      induction of autophagy. However, whether the neuroprotective effect of IGF-1 
      against excitotoxicity is mediated by autophagy through the PI3K/AKT/mTOR pathway 
      remains to be elucidated. The induction of autophagy following NMDA treatment was 
      determined by microtubule-associated protein light chain 3 (LC3) conversion and 
      the result of this autophagy was assessed by monitoring the cleavage of caspase 3 
      in cultured hippocampal neurons. Cell viability was determined using MTT and LDH 
      assay, and PI-staining was used to estimate the fate of autophagy and the 
      protective effect of IGF-1. In addition, IGF-1 was found to decrease autophagy 
      induced by NMDA using transmission electron microscopy and MDC staining. The 
      protective effect of IGF-1 against autophagy was accompanied with up-regulation 
      of phospho-AKT (p-AKT) and phospho-mTOR (p-mTOR), which was blocked by the 
      inhibitor of PI3K. At the same time, the activation of NR2B resulting in the 
      down-regulation of p-AKT and p-mTOR was blocked by IGF-1. Together, these data 
      suggest that NMDA induces the autophagy, followed by apoptosis in cultured 
      hippocampal neurons, and that IGF-1 can block this effect via inhibition of NR2B 
      receptors and activation of the PI3K-AKT-mTOR pathway.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Wang, Yansong
AU  - Wang Y
AD  - Department of Neurobiology and Beijing Institute for Brain Disorders, School of 
      Basic Medical Sciences, Capital Medical University, Beijing, P.R. China; 
      Department of Spine Surgery, Institute of Hard Tissue Development and 
      Regeneration of Harbin Medical University, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, Hei Long Jiang Province, P.R. China.
FAU - Wang, Wei
AU  - Wang W
FAU - Li, Dongguo
AU  - Li D
FAU - Li, Mi
AU  - Li M
FAU - Wang, Peipei
AU  - Wang P
FAU - Wen, Jian
AU  - Wen J
FAU - Liang, Min
AU  - Liang M
FAU - Su, Bo
AU  - Su B
FAU - Yin, Yanling
AU  - Yin Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, rat)
RN  - 0 (LC3 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Neurotoxins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 17885-08-4 (Phosphoserine)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/*drug effects
MH  - Beclin-1
MH  - Caspase 3/metabolism
MH  - Cells, Cultured
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Female
MH  - Hippocampus/*pathology
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Microtubule-Associated Proteins/metabolism
MH  - Models, Biological
MH  - N-Methylaspartate/*toxicity
MH  - Neurons/drug effects/enzymology/*pathology/ultrastructure
MH  - Neurotoxins/*toxicity
MH  - Phagosomes/drug effects/metabolism/ultrastructure
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphorylation/drug effects
MH  - Phosphoserine/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Signal Transduction/*drug effects
MH  - Synapses/drug effects/metabolism/ultrastructure
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2014/03/08 06:00
MHDA- 2014/09/26 06:00
CRDT- 2014/03/08 06:00
PHST- 2013/10/28 00:00 [received]
PHST- 2014/03/05 00:00 [accepted]
PHST- 2014/03/08 06:00 [entrez]
PHST- 2014/03/08 06:00 [pubmed]
PHST- 2014/09/26 06:00 [medline]
AID - 10.1002/jcp.24607 [doi]
PST - ppublish
SO  - J Cell Physiol. 2014 Nov;229(11):1618-29. doi: 10.1002/jcp.24607.