Anastasiadis P Z, Bezin L, Imerman B A, Kuhn D M, Louie M C, Levine R A
William T. Gossett Neurology Laboratories of Henry Ford Hospital, Detroit, MI 48202, USA.
Eur J Neurosci. 1997 Sep;9(9):1831-7. doi: 10.1111/j.1460-9568.1997.tb00749.x.
Epidermal growth factor and nerve growth factor increased the proliferation of rat phaeochromocytoma PC12 cells through obligatory elevation of intracellular (6R)-tetrahydrobiopterin (BH4). Epidermal growth factor and nerve growth factor increased intracellular BH4 by inducing GTP-cyclohydrolase, the rate-limiting enzyme in BH4 biosynthesis. Specific inhibitors of BH4 biosynthesis prevented growth factor-induced increases in BH4 levels and proliferation. The induction of GTP cyclohydrolase, BH4 and cellular proliferation by nerve growth factor was mediated by cAMP. Elevation of BH4 biosynthesis occurred downstream from cAMP in the cascade used by nerve growth factor to increase proliferation. Thus, intracellular BH4 is an essential mediator of the proliferative effects of epidermal growth factor and nerve growth factor in PC12 cells.
表皮生长因子和神经生长因子通过细胞内（6R）-四氢生物蝶呤（BH4）的必然升高，增加大鼠嗜铬细胞瘤PC12细胞的增殖。表皮生长因子和神经生长因子通过诱导GTP-环化水解酶（BH4生物合成中的限速酶）来增加细胞内BH4。BH4生物合成的特异性抑制剂可阻止生长因子诱导的BH4水平升高和细胞增殖。神经生长因子对GTP环化水解酶、BH4和细胞增殖的诱导作用是由cAMP介导的。在神经生长因子用于增加增殖的级联反应中，BH4生物合成的升高发生在cAMP下游。因此，细胞内BH4是表皮生长因子和神经生长因子在PC12细胞中增殖作用的重要介质。
