PMID- 17548347
OWN - NLM
STAT- MEDLINE
DCOM- 20070913
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 31
DP  - 2007 Aug 3
TI  - Neural precursor cells are protected from apoptosis induced by trophic factor 
      withdrawal or genotoxic stress by inhibitors of glycogen synthase kinase 3.
PG  - 22856-64
AB  - Mechanisms controlling the survival of neural precursor cells (NPCs) are critical 
      during brain development, in adults for neuron replenishment, and after 
      transplantation for neuron replacement. This investigation found that glycogen 
      synthase kinase 3 (GSK3) promotes apoptotic signaling in cultured NPCs derived 
      from embryonic mouse brain subjected to two common apoptotic conditions, trophic 
      factor withdrawal and genotoxic stress. Trophic factor withdrawal activated GSK3 
      and the key apoptosis mediators Bax and caspase-3. Pharmacological inhibition of 
      GSK3 activity produced dramatic reductions in the activation of Bax and caspase-3 
      and NPC death after trophic factor withdrawal. Trophic factor withdrawal-induced 
      apoptosis was delayed in Bax knock-out NPCs, but GSK3 inhibitors provided 
      additional protection. Genotoxic stress induced by camptothecin treatment of NPCs 
      stabilized p53, which formed a complex with GSK3beta and activated Bax and 
      caspase-3. Camptothecin-induced activation of caspase-3 was reduced by GSK3 
      inhibitors in both bax(+)(/)(+) and bax(-/-) NPCs. Thus, NPCs are sensitive to 
      loss of trophic factors and genotoxic stress, and inhibitors of GSK3 are capable 
      of enhancing NPC survival.
FAU - Eom, Tae-Yeon
AU  - Eom TY
AD  - Department of Psychiatry and Behavioral Neurobiology, University of Alabama at 
      Birmingham, Birmingham, Alabama 35294-0017, USA.
FAU - Roth, Kevin A
AU  - Roth KA
FAU - Jope, Richard S
AU  - Jope RS
LA  - eng
GR  - R01 NS041962/NS/NINDS NIH HHS/United States
GR  - AG021045/AG/NIA NIH HHS/United States
GR  - R01 NS037768/NS/NINDS NIH HHS/United States
GR  - R01 AG021045-05/AG/NIA NIH HHS/United States
GR  - R01 MH038752-23/MH/NIMH NIH HHS/United States
GR  - R56 MH038752/MH/NIMH NIH HHS/United States
GR  - NS41962/NS/NINDS NIH HHS/United States
GR  - MH38752/MH/NIMH NIH HHS/United States
GR  - R01 NS037768-08/NS/NINDS NIH HHS/United States
GR  - R01 MH038752/MH/NIMH NIH HHS/United States
GR  - R01 AG021045/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070604
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.4.22.- (Caspase 3)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Camptothecin/pharmacology
MH  - Caspase 3/metabolism
MH  - Cells, Cultured/cytology
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Neurons/*cytology
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Time Factors
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC2140256
MID - NIHMS28399
EDAT- 2007/06/06 09:00
MHDA- 2007/09/14 09:00
PMCR- 2007/12/17
CRDT- 2007/06/06 09:00
PHST- 2007/06/06 09:00 [pubmed]
PHST- 2007/09/14 09:00 [medline]
PHST- 2007/06/06 09:00 [entrez]
PHST- 2007/12/17 00:00 [pmc-release]
AID - S0021-9258(20)54743-1 [pii]
AID - 10.1074/jbc.M702973200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Aug 3;282(31):22856-64. doi: 10.1074/jbc.M702973200. Epub 2007 
      Jun 4.