PMID- 23608221
OWN - NLM
STAT- MEDLINE
DCOM- 20130731
LR  - 20191210
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 218
IP  - 1
DP  - 2013 Jul
TI  - Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal 
      neural stem cells.
PG  - 49-59
LID - 10.1530/JOE-13-0045 [doi]
AB  - Ghrelin, an endogenous ligand for the GH secretagogue receptor (GHS-R) receptor 
      1a (GHS-R1a), has been implicated in several physiologic processes involving the 
      hippocampus. The aim of this study was to investigate the molecular mechanisms of 
      ghrelin-stimulated neurogenesis using cultured adult rat hippocampal neural stem 
      cells (NSCs). The expression of GHS-R1a was detected in hippocampal NSCs, as 
      assessed by western blot analysis and immunocytochemistry. Ghrelin treatment 
      increased the proliferation of cultured hippocampal NSCs assessed by BrdU 
      incorporation. The exposure of cells to the receptor-specific antagonist 
      d-Lys-3-GHRP-6 abolished the proliferative effect of ghrelin. By contrast, 
      ghrelin showed no significant effect on cell differentiation. The expression of 
      GHS-R1a was significantly increased by ghrelin treatment. The analysis of 
      signaling pathways showed that ghrelin caused rapid activation of ERK1/2 and Akt, 
      which were blocked by the GHS-R1a antagonist. In addition, ghrelin stimulated the 
      phosphorylation of Akt downstream effectors, such as glycogen synthase kinase 
      (GSK)-3beta, mammalian target of rapamycin (mTOR), and p70(S6K). The activation of 
      STAT3 was also caused by ghrelin treatment. Furthermore, pretreatment of cells 
      with specific inhibitors of MEK/ERK1/2, phosphatidylinositol-3-kinase (PI3K)/Akt, 
      mTOR, and Jak2/STAT3 attenuated ghrelin-induced cell proliferation. Taken 
      together, our results support a role for ghrelin in adult hippocampal 
      neurogenesis and suggest the involvement of the ERK1/2, PI3K/Akt, and STAT3 
      signaling pathways in the mediation of the actions of ghrelin on neurogenesis. 
      Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3beta and 
      activation of mTOR/p70(S6K) contribute to the proliferative effect of ghrelin.
FAU - Chung, Hyunju
AU  - Chung H
AD  - Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee 
      University Hospital at Gangdong, Seoul, Korea.
FAU - Li, Endan
AU  - Li E
FAU - Kim, Yumi
AU  - Kim Y
FAU - Kim, Sehee
AU  - Kim S
FAU - Park, Seungjoon
AU  - Park S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130601
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ghrelin)
RN  - 0 (Ghsr1a protein, rat)
RN  - 0 (Hormone Antagonists)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Receptors, Ghrelin)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
SB  - IM
MH  - Adult Stem Cells/cytology/drug effects/*metabolism
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/pharmacology
MH  - Ghrelin/antagonists & inhibitors/genetics/*metabolism
MH  - Hippocampus/cytology/drug effects/*metabolism
MH  - Hormone Antagonists/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Neural Stem Cells/cytology/drug effects/*metabolism
MH  - *Neurogenesis/drug effects
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Ghrelin/antagonists & inhibitors/biosynthesis/*metabolism
MH  - Recombinant Proteins/antagonists & inhibitors/metabolism
MH  - STAT3 Transcription Factor/antagonists & inhibitors/metabolism
MH  - *Signal Transduction/drug effects
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - ghrelin
OT  - hippocampus
OT  - progenitor
OT  - proliferation
OT  - signaling pathways
EDAT- 2013/04/24 06:00
MHDA- 2013/08/01 06:00
CRDT- 2013/04/24 06:00
PHST- 2013/04/24 06:00 [entrez]
PHST- 2013/04/24 06:00 [pubmed]
PHST- 2013/08/01 06:00 [medline]
AID - JOE-13-0045 [pii]
AID - 10.1530/JOE-13-0045 [doi]
PST - epublish
SO  - J Endocrinol. 2013 Jun 1;218(1):49-59. doi: 10.1530/JOE-13-0045. Print 2013 Jul.