Uridine induces differentiation in human neuroblastoma cells via protein kinase C epsilon

Uridine metabolism has an important role in the physiopathology of the nervous system. In this paper, we have explored the effects of exogenous uridine on LAN-5 human neuroblastoma cells. Cells were exposed to uridine for 4 days and cell proliferation, neurite outgrowth, and 160 kDa neurofilament (NF) expression were the parameters measured. Our results showed that 10 microg/ml uridine decreased cell proliferation, this effect being associated with an increase in cell differentiation, as evidenced by neurite outgrowth and NF expression. These effects can be prevented by dipyridamole (10 microM), an inhibitor of nucleotides and nucleosides uptake. In the literature, neuroblastoma cells differentiation has been demonstrated to involve Protein Kinase C epsilon (PKCepsilon). After treatment with uridine, we observed in LAN-5 cells an increase in PKCepsilon protein level. This increase was inhibited by dipyridamole. Moreover, the increase of neurite outgrowth induced by uridine was inhibited by treatment with bisindolylmaleimide I (GF109203X), an inhibitor of PKC. Our data suggest that PKCepsilon is involved in uridine-induced cell differentiation in human neuroblastoma cells.