PMID- 19111604
OWN - NLM
STAT- MEDLINE
DCOM- 20090518
LR  - 20200106
IS  - 1873-474X (Electronic)
IS  - 0736-5748 (Linking)
VI  - 27
IP  - 2
DP  - 2009 Apr
TI  - Extracellular guanosine and GTP promote expression of differentiation markers and 
      induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells.
PG  - 135-47
LID - 10.1016/j.ijdevneu.2008.11.007 [doi]
AB  - SH-SY5Y neuroblastoma cells, a model for studying neuronal differentiation, are 
      able to differentiate into either cholinergic or dopaminergic/adrenergic 
      phenotypes depending on media conditions. Using this system, we asked whether 
      guanosine (Guo) or guanosine-5'-triphosphate (GTP) are able to drive 
      differentiation towards one particular phenotype. Differentiation was determined 
      by evaluating the frequency of cells bearing neurites and assessing neurite 
      length after exposure to different concentrations of Guo or GTP for different 
      durations. After 6 days, 0.3 mM Guo or GTP induced a significant increase in the 
      number of cells bearing neurites and increased neurite length. Western blot 
      analyses confirmed that purines induced differentiation; cells exposed to purines 
      showed increases in the levels of GAP43, MAP2, and tyrosine hydroxylase. 
      Proliferation assays and cytofluorimetric analyses indicated a significant 
      anti-proliferative effect of purines, and a concentration-dependent accumulation 
      of cells in S-phase, starting after 24 h of purine exposure and extending for up 
      to 6 days. A transcriptional profile analysis using gene arrays showed that an 
      up-regulation of cyclin E2/cdk2 evident after 24 h was responsible for S-phase 
      entry, and a concurrent down-regulation of cell-cycle progression-promoting 
      cyclin B1/B2 prevented S-phase exit. In addition, patch-clamp recordings revealed 
      that 0.3 mM Guo or GTP, after 6 day incubation, significantly decreased Na(+) 
      currents. In conclusion, we showed Guo- and GTP-induced cell-cycle arrest in 
      neuroblastoma cells and suggest that this makes these cells more responsive to 
      differentiation processes that favor the dopaminergic/adrenergic phenotype.
FAU - Guarnieri, S
AU  - Guarnieri S
AD  - Dipartamento Scienze Mediche di Base ed Applicate Universita G. d'Annunzio, 
      Chieti, Italy.
FAU - Pilla, R
AU  - Pilla R
FAU - Morabito, C
AU  - Morabito C
FAU - Sacchetti, S
AU  - Sacchetti S
FAU - Mancinelli, R
AU  - Mancinelli R
FAU - Fano, G
AU  - Fano G
FAU - Mariggio, M A
AU  - Mariggio MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081206
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - 0 (CCNB1 protein, human)
RN  - 0 (CCNB2 protein, human)
RN  - 0 (CCNE2 protein, human)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (Cyclin B2)
RN  - 0 (Cyclins)
RN  - 0 (GAP-43 Protein)
RN  - 0 (MAP2 protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 12133JR80S (Guanosine)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cyclin B/metabolism
MH  - Cyclin B1
MH  - Cyclin B2
MH  - Cyclin-Dependent Kinase 2/metabolism
MH  - Cyclins/metabolism
MH  - Down-Regulation
MH  - Extracellular Space/metabolism
MH  - GAP-43 Protein/metabolism
MH  - Guanosine/*metabolism
MH  - Guanosine Triphosphate/*metabolism
MH  - Humans
MH  - Membrane Potentials
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neurites/physiology
MH  - *Neurogenesis
MH  - Neurons/*cytology/physiology
MH  - *S Phase
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Up-Regulation
EDAT- 2008/12/30 09:00
MHDA- 2009/05/19 09:00
CRDT- 2008/12/30 09:00
PHST- 2008/09/23 00:00 [received]
PHST- 2008/11/04 00:00 [revised]
PHST- 2008/11/29 00:00 [accepted]
PHST- 2008/12/30 09:00 [entrez]
PHST- 2008/12/30 09:00 [pubmed]
PHST- 2009/05/19 09:00 [medline]
AID - S0736-5748(08)00365-1 [pii]
AID - 10.1016/j.ijdevneu.2008.11.007 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2009 Apr;27(2):135-47. doi: 10.1016/j.ijdevneu.2008.11.007. 
      Epub 2008 Dec 6.