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

Uridine metabolism has an important role in the physiopathology of the nerv ous system. In this paper, we have explored the effects of exogenous uridin e on LAN-5 human neuroblastoma cells. Cells were exposed to uridine for 4 d ays and cell proliferation, neurite outgrowth, and 160 kDa neurofilament (N F) expression were the parameters measured. Our results showed that 10 mu g /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 mu M), a n inhibitor of nucleotides and nucleosides uptake. In the literature, neuro blastoma cells differentiation has been demonstrated to involve Protein Kin ase C epsilon (PKC epsilon). After treatment with uridine, we observed in L AN-5 cells an increase in PKC epsilon protein level, This increase was inhi bited 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 PKC epsilon is involved in ur idine-induced cell differentiation in human neuroblastoma cells. (C) 2000 W iley-Liss, Inc.