Document Detail

Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected]
MedLine Citation:
PMID:  15939540     Owner:  NLM     Status:  MEDLINE    
During rapid cell growth the availability of phospholipid precursors like cytidine triphosphate and diacylglycerol can become limiting in the formation of key membrane constituents like phosphatidylcholine. Uridine, a normal plasma constituent, can be converted to cytidine triphosphate in PC12 [corrected] cells and intact brain, and has been shown to produce a resulting increase in phosphatidylcholine synthesis. To determine whether treatments that elevate uridine availability also thereby augment membrane production, we exposed PC12 [corrected] cells which had been differentiated by nerve growth factor to various concentrations of uridine, and measured the numbers of neurites the cells produced. After 4 but not 2 days uridine significantly and dose-dependently increased the number of neurites per cell. This increase was accompanied by increases in neurite branching and in levels of the neurite proteins neurofilament M [corrected] and neurofilament 70. Uridine treatment also increased intracellular levels of cytidine triphosphate, which suggests that uridine may affect neurite outgrowth by enhancing phosphatidylcholine synthesis. Uridine may also stimulate neuritogenesis by a second mechanism, since the increase in neurite outgrowth was mimicked by exposing the cells to uridine triphosphate, and could be blocked by various drugs known to antagonize P2Y receptors (suramin; Reactive Blue 2; pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid). Treatment of the cells with uridine or uridine triphosphate stimulated their accumulation of inositol phosphates, and this effect was also blocked by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid. Moreover, degradation of nucleotides by apyrase blocked the stimulatory effect of uridine on neuritogenesis. Taken together these data indicate that uridine can regulate the output of neurites from differentiating PC12 [corrected] cells, and suggest that it does so in two ways, i.e. both by acting through cytidine triphosphate as a precursor for phosphatidylcholine biosynthesis and through uridine triphosphate as an agonist for P2Y receptors.
A M Pooler; D H Guez; R Benedictus; R J Wurtman
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroscience     Volume:  134     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2005  
Date Detail:
Created Date:  2005-07-11     Completed Date:  2005-12-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  207-14     Citation Subset:  IM    
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 45 Carleton Street, Cambridge, MA 02139, USA.
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MeSH Terms
Analysis of Variance
Apyrase / pharmacology
Blotting, Western / methods
Cell Differentiation / drug effects*
Cytidine Triphosphate / metabolism
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology
Gene Expression Regulation / drug effects
Immunohistochemistry / methods
Intermediate Filament Proteins / metabolism
Nerve Growth Factor / pharmacology*
Neurites / drug effects*
Neurofilament Proteins / metabolism
PC12 Cells
Pheochromocytoma / pathology*
Phosphatidylinositols / metabolism
Receptors, Purinergic P2 / metabolism
Time Factors
Uridine / pharmacology*
Uridine Triphosphate / metabolism,  pharmacology
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Intermediate Filament Proteins; 0/Neurofilament Proteins; 0/Phosphatidylinositols; 0/Receptors, Purinergic P2; 111365-29-8/neurofilament protein M; 143221-02-7/neurofilament protein NF 70; 58-96-8/Uridine; 63-39-8/Uridine Triphosphate; 65-47-4/Cytidine Triphosphate; 9061-61-4/Nerve Growth Factor; EC
Erratum In:
Neuroscience. 2005;135(2):657

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