Possible involvement of tetrahydrobiopterin in the trophic effect of insulin-like growth factor-1 on rat pheochromocytoma-12 (PC12) cells.
Tetrahydrobiopterin (BH(4)) has a trophic effect on pheochromocytoma-12 (PC12) cells such as insulin-like growth factor-1 (IGF-1). We investigated involvement of BH(4) in the trophic effect of IGF-1 on PC12 cells. IGF-1 (10-300 ng/ml) increased cellular BH(4) content in a dose-related manner. Cellular BH(4) content increased after 6-36 h incubation with IGF-1. IGF-1-induced increase in the cellular BH(4) content was blunted by 0.3 mM 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor for BH(4) synthesis. IGF-1 protected PC12 cells from the cell death induced by depletion of serum and nerve growth factor, which was attenuated by DAHP. The effects of IGF-1 on the cellular BH(4) content and cell viability were eliminated by 0.2 microM wortmannin. These results suggest that BH(4) is involved in the trophic effect of IGF-1 on PC12 cells and that the effect of IGF-1 on BH(4) synthesis is mediated by phosphatidylinositol 3-kinase.
First Division, Department of Medicine, Shimane Medical University, Izumo 693-8501, Japan.
Junko
J
Tanaka
Kunio
K
Koshimura
Yoshio
Y
Murakami
Yuzuru
Y
Kato
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007042:Hypoxanthines / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000172:deficiency; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D000077191:Wortmannin
D000730:Androstadienes; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007042:Hypoxanthines; D009414:Nerve Growth Factors; D001708:Biopterins; D007334:Insulin-Like Growth Factor I; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C017202:2,4-diaminohypoxanthine; C003402:sapropterin; D000077191:Wortmannin