Mocchetti I, De Bernardi M A, Szekely A M, Alho H, Brooker G, Costa E
Fidia-Georgetown Institute for the Neurosciences, Georgetown University, School of Medicine, Washington, DC 20007.
Proc Natl Acad Sci U S A. 1989 May;86(10):3891-5. doi: 10.1073/pnas.86.10.3891.
The chain of events that results in increased production of nerve growth factor (NGF) following beta-adrenergic receptor (BAR) stimulation has been investigated in the C6-2B rat astrocytoma cell line. Exposure of these cells to the BAR agonist isoproterenol elicits the following cascade of events: (i) increase of cAMP content; (ii) increase of c-Fos mRNA content; (iii) accumulation of c-Fos protein immunoreactivity in the nucleus; (iv) increase of NGF mRNA content. The increase in c-Fos mRNA and its translation product are early events (15 and 40 min, respectively) and precede the accumulation of NGF mRNA, which peaks at 3 hr. The increase in the two mRNAs appears interrelated because cycloheximide inhibits the accumulation of c-Fos protein and NGF mRNA elicited by isoproterenol. Moreover, the accumulation of nuclear c-Fos protein and NGF mRNA induced by BAR stimulation is reduced by 2-aminopurine, an inhibitor of c-Fos mRNA induction. These data suggest that, in C6-2B astrocytoma cells, the nuclear accumulation of c-Fos protein is required for the induction of NGF mRNA expression by BAR stimulation.
在C6 - 2B大鼠星形细胞瘤细胞系中,研究了β - 肾上腺素能受体(BAR)刺激后导致神经生长因子(NGF)产量增加的一系列事件。将这些细胞暴露于BAR激动剂异丙肾上腺素会引发以下一系列事件:(i)cAMP含量增加;(ii)c - Fos mRNA含量增加;(iii)c - Fos蛋白免疫反应性在细胞核中积累;(iv)NGF mRNA含量增加。c - Fos mRNA及其翻译产物的增加是早期事件(分别为15分钟和40分钟),且先于NGF mRNA的积累,NGF mRNA在3小时达到峰值。两种mRNA的增加似乎相互关联,因为环己酰亚胺抑制了异丙肾上腺素引起的c - Fos蛋白和NGF mRNA的积累。此外,BAR刺激诱导的细胞核c - Fos蛋白和NGF mRNA的积累被2 - 氨基嘌呤(一种c - Fos mRNA诱导抑制剂)减少。这些数据表明,在C6 - 2B星形细胞瘤细胞中,BAR刺激诱导NGF mRNA表达需要c - Fos蛋白在细胞核中积累。