D'Mello S R, Jiang C, Lamberti C, Martin S C, Heinrich G
Evans Department of Clinical Research, University Hospital, Boston, Massachusetts 02118.
J Neurosci Res. 1992 Dec;33(4):519-26. doi: 10.1002/jnr.490330404.
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are structurally related survival and differentiation factors for distinct sets of peripheral and central neurons. The regulation of NGF gene expression has been extensively studied in L929 mouse fibroblasts. L929 cells also express the BDNF gene. Northern blot hybridization analysis revealed 4 discrete BDNF mRNA species in L929 cells and rat hippocampus after induction of seizures with kainic acid. Serum as well as 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulated NGF and all 4 BDNF mRNAs in L929 cells. Treatment with both agents induced NGF mRNA to a much larger extent than the BDNF mRNAs. The induction of the BDNF mRNAs was rapid, with nearly maximal levels by 1 hr. In contrast, NGF mRNA induction occurred later and peaked at 4-6 hr. Both NGF and BDNF mRNA induction were inhibited by actinomycin D. Cycloheximide, on the other hand, inhibited only NGF but not BDNF mRNA induction. Corticosterone rapidly decreased NGF mRNA but not the BDNF mRNAs, and had no effect on seizure-induced NGF or BDNF mRNAs. Forskolin did not stimulate NGF or BDNF mRNAs. In contrast to NGF mRNA, forskolin did not interfere with the serum induction of BDNF mRNAs. These results demonstrate that 2 genes which encode closely related neurotrophic factors are differentially regulated in L929 cells. The molecular mechanisms which bring about this differential regulation remain to be elucidated.
神经生长因子（NGF）和脑源性神经营养因子（BDNF）是在结构上相关的存活和分化因子，作用于不同的外周和中枢神经元群体。NGF基因表达的调控已在L929小鼠成纤维细胞中得到广泛研究。L929细胞也表达BDNF基因。用 kainic 酸诱导癫痫发作后，Northern 印迹杂交分析显示 L929 细胞和大鼠海马体中有 4 种离散的 BDNF mRNA 种类。血清以及 12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）刺激 L929 细胞中的 NGF 和所有 4 种 BDNF mRNA。两种试剂处理诱导 NGF mRNA 的程度比 BDNF mRNA 大得多。BDNF mRNA 的诱导迅速，1 小时时达到近最大水平。相比之下，NGF mRNA 的诱导发生较晚，在 4 - 6 小时达到峰值。放线菌素 D 抑制 NGF 和 BDNF mRNA 的诱导。另一方面，环己酰亚胺仅抑制 NGF 而不抑制 BDNF mRNA 的诱导。皮质酮迅速降低 NGF mRNA 但不降低 BDNF mRNA，并且对癫痫发作诱导的 NGF 或 BDNF mRNA 没有影响。福斯可林不刺激 NGF 或 BDNF mRNA。与 NGF mRNA 相反，福斯可林不干扰血清对 BDNF mRNA 的诱导。这些结果表明，在 L929 细胞中，编码密切相关神经营养因子的两个基因受到不同的调控。导致这种差异调控的分子机制仍有待阐明。
