PMID- 18047416
OWN - NLM
STAT- MEDLINE
DCOM- 20080310
LR  - 20131121
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 16
IP  - 6
DP  - 2007 Dec
TI  - Anti-apoptotic effect of sphingosine-1-phosphate and platelet-derived growth 
      factor in human embryonic stem cells.
PG  - 989-1001
AB  - Human embryonic stem (hES) cells hold great promise for use in regenerative 
      medicine. However, technologies first need to be established to maintain hES 
      cells efficiently in vitro. Understanding the signaling networks involved in hES 
      cell maintenance will prove to be essential to the development of such culture 
      systems. Previously, we described a serum-free medium capable of supporting 
      prolonged hES cell maintenance using sphingosine-1-phosphate (S1P) and 
      platelet-derived growth factor (PDGF). Here, we describe an anti-apoptotic effect 
      of S1P and PDGF in hES cells and demonstrate a direct effect of S1P in preventing 
      hES cell apoptosis. Western blot analysis shows that S1P stimulates the 
      phosphorylation of the mitogen-activated protein (MAP) kinases Erk1/2 but not of 
      Akt, whereas PDGF stimulates both Erk1/2 and Akt phosphorylation. Moreover, our 
      study suggests that the Erk1/2 and PI3K/Akt signaling pathways act independently 
      of each other. Furthermore, neither S1P nor PDGF modify intracellular calcium 
      concentration ([Ca(2+)]( i )) and Smad2 phosphorylation. Using pharmacological 
      inhibitors of Erk1/2 and PI3K, our results demonstrate a critical role of the 
      Erk1/2 and PI3K/Akt signaling pathways in mediating the anti-apoptotic effect of 
      S1P and PDGF on hES cells. However, inhibition of the mammalian target of 
      rapamycin (mTOR), a common downstream effector of Erk1/2 and PI3K/Akt, has no 
      effect on hES cell apoptosis.
FAU - Wong, Raymond C B
AU  - Wong RC
AD  - Monash Institute of Medical Research, Monash University, Clayton, Victoria 3168, 
      Australia.
FAU - Tellis, Irene
AU  - Tellis I
FAU - Jamshidi, Pegah
AU  - Jamshidi P
FAU - Pera, Martin
AU  - Pera M
FAU - Pebay, Alice
AU  - Pebay A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Lysophospholipids)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - NGZ37HRE42 (Sphingosine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Calcium/pharmacology
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Embryonic Stem Cells/*cytology/drug effects/*physiology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Lysophospholipids/*pharmacology
MH  - Mice
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/*pharmacology
MH  - Sphingosine/*analogs & derivatives/pharmacology
EDAT- 2007/12/01 09:00
MHDA- 2008/03/11 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/03/11 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - 10.1089/scd.2007.0057 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2007 Dec;16(6):989-1001. doi: 10.1089/scd.2007.0057.