PMID- 16313513
OWN - NLM
STAT- MEDLINE
DCOM- 20060207
LR  - 20161124
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 95
IP  - 5
DP  - 2005 Dec
TI  - Novel role of sphingosine kinase 1 as a mediator of neurotrophin-3 action in 
      oligodendrocyte progenitors.
PG  - 1298-310
AB  - We had found previously that neurotrophin-3 (NT-3) is a potent stimulator of 
      cAMP-response element binding protein (CREB) phosphorylation in cultured 
      oligodendrocyte progenitors. Here, we show that CREB phosphorylation in these 
      cells is also highly stimulated by sphingosine-1-phosphate (S1P), a sphingolipid 
      metabolite that is known to be a potent mediator of numerous biological 
      processes. Moreover, CREB phosphorylation in response to NT-3 involves 
      sphingosine kinase 1 (SphK1), the enzyme that synthesizes S1P. 
      Immunocytochemistry and confocal microscopy indicated that NT-3 induces 
      translocation of SphK1 from the cytoplasm to the plasma membrane of 
      oligodendrocytes, a process accompanied by increased SphK1 activity in the 
      membrane fraction where its substrate sphingosine resides. To examine the 
      involvement of SphK1 in NT-3 function, SphK1 expression was down-regulated by 
      treatment with SphK1 sequence-specific small interfering RNA. Remarkably, the 
      capacity of NT-3 to protect oligodendrocyte progenitors from apoptotic cell death 
      induced by growth factor deprivation was abolished by down-regulating the 
      expression of SphK1, as assessed by terminal deoxynucleotidyl transferase dUTP 
      nick-end labeling (TUNEL) assay. Altogether, these results suggest that SphK1 
      plays a crucial role in the stimulation of oligodendrocyte progenitor survival by 
      NT-3, and demonstrate a functional link between NT-3 and S1P signaling, adding to 
      the complexity of mechanisms that modulate neurotrophin function and 
      oligodendrocyte development.
FAU - Saini, Harsimran S
AU  - Saini HS
AD  - Department of Biochemistry, Virginia Commonwealth University School of Medicine, 
      Richmond, Virginia 23298-0614, USA.
FAU - Coelho, Rochelle P
AU  - Coelho RP
FAU - Goparaju, Sravan K
AU  - Goparaju SK
FAU - Jolly, Puneet S
AU  - Jolly PS
FAU - Maceyka, Michael
AU  - Maceyka M
FAU - Spiegel, Sarah
AU  - Spiegel S
FAU - Sato-Bigbee, Carmen
AU  - Sato-Bigbee C
LA  - eng
GR  - 1CO6RR17393/CO/NCI NIH HHS/United States
GR  - F31 NS 48 733-01A1/NS/NINDS NIH HHS/United States
GR  - GM43880/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Lysophospholipids)
RN  - 0 (Neurotrophin 3)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Thiones)
RN  - 0 (thiazolidine-2,4-thione)
RN  - 19794-97-9 (dihydrosphingosine 1-phosphate)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - L9QRA71834 (N,N-dimethylsphingosine)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Blotting, Western/methods
MH  - Cell Membrane/drug effects/metabolism
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Drug Interactions
MH  - Gene Expression Regulation/drug effects
MH  - In Situ Nick-End Labeling/methods
MH  - Lysophospholipids/pharmacology
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Biological
MH  - Neurotrophin 3/*pharmacology
MH  - *Oligodendroglia
MH  - Phosphorylation/drug effects
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Protein Kinase C/pharmacology
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - Stem Cells/*drug effects/physiology
MH  - Thiazoles/pharmacology
MH  - Thiazolidinediones
MH  - Thiones/pharmacology
MH  - Time Factors
EDAT- 2005/11/30 09:00
MHDA- 2006/02/08 09:00
CRDT- 2005/11/30 09:00
PHST- 2005/11/30 09:00 [pubmed]
PHST- 2006/02/08 09:00 [medline]
PHST- 2005/11/30 09:00 [entrez]
AID - JNC3451 [pii]
AID - 10.1111/j.1471-4159.2005.03451.x [doi]
PST - ppublish
SO  - J Neurochem. 2005 Dec;95(5):1298-310. doi: 10.1111/j.1471-4159.2005.03451.x.