Document Detail

Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells.
MedLine Citation:
PMID:  19111604     Owner:  NLM     Status:  MEDLINE    
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.
S Guarnieri; R Pilla; C Morabito; S Sacchetti; R Mancinelli; G Fanò; M A Mariggiò
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-06
Journal Detail:
Title:  International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience     Volume:  27     ISSN:  1873-474X     ISO Abbreviation:  Int. J. Dev. Neurosci.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-02-03     Completed Date:  2009-05-18     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8401784     Medline TA:  Int J Dev Neurosci     Country:  England    
Other Details:
Languages:  eng     Pagination:  135-47     Citation Subset:  IM    
Dipartamento Scienze Mediche di Base ed Applicate Università G. d'Annunzio, Chieti, Italy.
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MeSH Terms
Cell Line, Tumor
Cyclin B / metabolism
Cyclin B1
Cyclin B2
Cyclin-Dependent Kinase 2 / metabolism
Cyclins / metabolism
Extracellular Space / metabolism
GAP-43 Protein / metabolism
Guanosine / metabolism*
Guanosine Triphosphate / metabolism*
Membrane Potentials
Microtubule-Associated Proteins / metabolism
Neurites / physiology
Neurons / cytology*,  physiology
S Phase*
Tyrosine 3-Monooxygenase / metabolism
Reg. No./Substance:
0/CCNB1 protein, human; 0/CCNB2 protein, human; 0/CCNE2 protein, human; 0/Cyclin B; 0/Cyclin B1; 0/Cyclin B2; 0/Cyclins; 0/GAP-43 Protein; 0/MAP2 protein, human; 0/Microtubule-Associated Proteins; 118-00-3/Guanosine; 86-01-1/Guanosine Triphosphate; EC 3-Monooxygenase; EC protein, human; EC Kinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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