Involvement of tetrahydrobiopterin in trophic effect of erythropoietin on PC12 cells

Tetrahydrobiopterin (BH4) synthesis is reported to be stimulated by nerve g rowth factor (NGF) in PC12 cells, suggesting involvement of BH4 in the trop hic effect of NGF. We have recently reported that erythropoietin (EPO) and BH4, enhance survival of PC12 cells. In the present study, we investigated involvement of BH4 in the trophic effect of EPO on PC 12 cells. Cellular BH 4 content was increased by EPO (10(-10) to 10(-8) M) in a dose- and time-re lated manner. EPO (10(-10) to 10(-8) M) increased the viable cell number of PC12 cells. In addition to EPO, BH4 (1, 3, and 10 muM) increased the viabl e cell number of PC 12 cells. Administration of 0.3 mM 2,4-diamino-6-hydrox ypyrimidine, an inhibitor of BH4 synthesis, blunted EPO-induced increases i n BH4 content and the viable cell number of PC12 cells. These results taken together suggest that BH4 is involved in the trophic effects of EPO on PC1 2 cells. (C) 2001 Elsevier Science.