Dragunow M, Xu R, Walton M, Woodgate A, Lawlor P, MacGibbon G A, Young D, Gibbons H, Lipski J, Muravlev A, Pearson A, During M
Department of Molecular Medicine, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Brain Res Mol Brain Res. 2000 Nov 10;83(1-2):20-33. doi: 10.1016/s0169-328x(00)00191-1.
We investigated the function of c-Jun in PC12 cells by transfecting them with a plasmid containing a c-Jun cDNA transcription cassette. Transfected cells expressed high levels of c-Jun mRNA and protein and demonstrated an increase in both AP-1 DNA binding and gene activation. The c-Jun over-expressing cells showed marked neurite outgrowth but no evidence of spontaneous cell death. In fact, c-Jun over-expressing cells were more resistant to okadaic acid-induced apoptosis. The process outgrowth was not indicative of a full neuronal differentiation response as the transfected PC12 cells did not display action potentials when examined with whole-cell patch-clamping. The phosphorylation of c-Jun on serine 73 appears to be important for this neurite sprouting effect as mutagenesis at this site reduced sprouting whereas a serine 63 mutant tended to increase sprouting. Thus, in PC12 cells c-Jun expression does not induce apoptosis, but rather functions as a neurite outgrowth and neuronal survival signal.
我们通过用含有c-Jun cDNA转录盒的质粒转染PC12细胞，研究了c-Jun在PC12细胞中的功能。转染后的细胞表达高水平的c-Jun mRNA和蛋白质，并显示出AP-1 DNA结合和基因激活均增加。过表达c-Jun的细胞表现出明显的神经突生长，但没有自发细胞死亡的迹象。事实上，过表达c-Jun的细胞对冈田酸诱导的细胞凋亡更具抗性。神经突生长过程并不表明是完全的神经元分化反应，因为用全细胞膜片钳检测时，转染的PC12细胞未显示动作电位。c-Jun丝氨酸73位点的磷酸化似乎对这种神经突萌发效应很重要，因为该位点的诱变会减少萌发，而丝氨酸63突变体则倾向于增加萌发。因此，在PC12细胞中，c-Jun的表达不会诱导细胞凋亡，而是作为神经突生长和神经元存活信号发挥作用。
