Involvement of tetrahydrobiopterin in trophic effect of erythropoietin on PC12 cells.
Tetrahydrobiopterin (BH(4)) synthesis is reported to be stimulated by nerve growth factor (NGF) in PC12 cells, suggesting involvement of BH(4) in the trophic effect of NGF. We have recently reported that erythropoietin (EPO) and BH(4) enhance survival of PC12 cells. In the present study, we investigated involvement of BH(4) in the trophic effect of EPO on PC12 cells. Cellular BH(4) content was increased by EPO (10(-10) to 10(-8) M) in a dose- and time-related manner. EPO (10(-10) to 10(-8) M) increased the viable cell number of PC12 cells. In addition to EPO, BH(4) (1, 3, and 10 microM) increased the viable cell number of PC12 cells. Administration of 0.3 mM 2,4-diamino-6-hydroxypyrimidine, an inhibitor of BH(4) synthesis, blunted EPO-induced increases in BH(4) content and the viable cell number of PC12 cells. These results taken together suggest that BH(4) is involved in the trophic effects of EPO on PC12 cells.
Tanaka
J
J
First Division, Department of Medicine, Shimane Medical University, Izumo, Japan.
Koshimura
K
K
Sohmiya
M
M
Murakami
Y
Y
Kato
Y
Y
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000378:metabolism*; D007042:Hypoxanthines / Q000494:pharmacology; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D004396:Coloring Agents; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007042:Hypoxanthines; D013778:Tetrazolium Salts; D013844:Thiazoles; D004921:Erythropoietin; D001708:Biopterins; C017202:2,4-diaminohypoxanthine; C003402:sapropterin; C022616:thiazolyl blue