Aim: 

Purines are growth factors participating in cell signalling, differentiation, proliferation and survival, as well as molecules mediating cellular degeneration and death (Franke and Illes, Pharmacol Ther. 109:297, 2006). The presence of extracellular guanine-based purines together with NGF induces synergistic neuritogenic effects promoting differentiation in noradrenergic PC12 cells (Guarnieri et al, Neuroscience 128:697, 2004). The aim of this study is to evaluate if these molecules are able to modulate the neuronal differentiation depending on neuronal phenotype. For these reason we used, as neuronal model, SH-SY5Y cells capable of differentiating in cholinergic or noradrenergic phenotype.

Methods: 

Differentiation was evaluated assessing neurite outgrowth and the expression of some neuronal-specific proteins. Cell growth and cycle were assayed by colorimetric and cytofluorimetric techniques, respectively. Whole-cell patch clamp experiments valuated cell electric activity.

Results: 

After 7 days of treatment, 0.3 mM Guo or GTP induced a significant increase in number of cells bearing neuritis and increased GAP43, MAP2 and tyrosine hydroxilase levels. Proliferation and cell cycle assays indicated a significant cell growth arrest and accumulation in the S-phase starting after 24 h of treatment, up to 7 days. After 7 days purine-treatment, cells showed a decrease in sodium currents.

Conclusion: 

In conclusion, we hypothesize that Guo or GTP are not classical neurotrophins, but are able to modulate neuroblastoma cell activity promoting cycle arrest and neuronal features probably to make cells more responsive to differentiative processes.