Herman M A, Schulz C A, Claude P
Department of Physiology, University of Wisconsin, Madison 53715.
Dev Biol. 1994 Feb;161(2):477-89. doi: 10.1006/dbio.1994.1046.
The nerve growth factor (NGF)-dependent transdifferentiation of adrenal chromaffin cells into sympathetic neurons occurs in two sequential phases: The first phase, in which cells extend neurites and increase proliferation, is mimicked by phorbol myristate acetate (PMA), an activator of protein kinase C. Analogs of cAMP, and forskolin, an activator of adenylate cyclase, antagonize the early effects of both NGF and PMA. The second phase of transdifferentiation, in which cells withdraw from the mitotic cycle and express a true neuronal phenotype, occurs after about 2 weeks of exposure to NGF and is neither mimicked by PMA alone nor antagonized by cAMP. Rather, cAMP promotes the neuronal phenotype of cells previously exposed to NGF or PMA. Thus NGF appears to activate different second messenger systems depending on the stage of differentiation of its target cells.
神经生长因子(NGF)依赖的肾上腺嗜铬细胞向交感神经元的转分化过程分为两个连续阶段:第一阶段,细胞伸出神经突并增加增殖,该阶段可被蛋白激酶C激活剂佛波酯(PMA)模拟。cAMP类似物以及腺苷酸环化酶激活剂福斯高林可拮抗NGF和PMA的早期作用。转分化的第二阶段,细胞退出有丝分裂周期并表达真正的神经元表型,该阶段在细胞暴露于NGF约2周后发生,既不能被单独的PMA模拟,也不能被cAMP拮抗。相反,cAMP可促进先前暴露于NGF或PMA的细胞的神经元表型。因此,NGF似乎根据其靶细胞的分化阶段激活不同的第二信使系统。