Nicotinamide-induced activity of alkaline phosphodiesterase I toward tumor-derived cultured cells from neurofibromatosis patients.
Membrane-bound alkaline phosphodiesterase I was investigated in control fibroblasts and tumor-derived fibroblasts from patients with neurofibromatosis. Alkaline phosphodiesterase I activity of tumor-derived cells increased in a dose response to nicotinamide (0-9 mM) in culture; 5'-thymidine p-nitrophenyl phosphate was used as substrate. The enzyme activity increased 1.7-fold after 30 h of incubation with 9 mM nicotinamide, and after 3 weeks increased 5-fold. The nicotinamide-dependent enhancement of alkaline phosphodiesterase I activity was inhibited by actinomycin D, which specifically blocks RNA synthesis, but not by cycloheximide. These results suggest that the increase in the enzyme activity caused by nicotinamide was due to induction of alkaline phosphodiesterase I at the transcriptional level in tumor-derived cells. The metabolic effect of nicotinamide on alkaline phosphodiesterase I may be related to tumorigenicity in neurofibromatosis.
Maruyama
E
E
Division of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Tokyo, Japan.
Takashima
S
S
Arima
M
M
D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D009456:Neurofibromatosis 1 / Q000201:enzymology*; D009536:Niacinamide / Q000494:pharmacology*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D009536:Niacinamide; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I