The c-Jun N-terminal kinases (JNKs) are important mediators of cell viability and structural integrity in postmitotic neurons, which is required for maintaining synaptic connections and neural plasticity. In the present study, we chose differentiated PC12 cells as a well-characterised neuronal model system to selectively examine the regulation of basal JNK activity by extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt. We detected a complex interaction between the kinases to prevent cell death and neurite loss. Especially the appropriate level of JNK activation determined cellular survival. Basal activity of ERK1/2 attenuated the potentiation of JNK phosphorylation and thereby the induction of apoptosis. Importantly, when JNK activity was too low, cell viability and the number of neurite-bearing cells also decreased, even though the activation of ERK1/2 was enhanced. In this case, the JNK-mediated survival signals via activating transcription factor-3 (ATF3) were inhibited. Furthermore, the phosphorylation of ERK1/2 induced by the JNK inhibitor SP600125 inhibited the basal activity of Akt, which normally supported cell viability. Thus, controlling JNK activity is crucial to promote survival and neurite stability of differentiated neuronal cells.

中文翻译：

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串扰控制和生理性c-Jun N末端激酶活性对分化PC12细胞中细胞活力和神经突稳定性的限制。

c-Jun N末端激酶（JNKs）是有丝分裂后神经元中细胞活力和结构完整性的重要介体，这是维持突触连接和神经可塑性所必需的。在本研究中，我们选择分化的PC12细胞作为功能完善的神经元模型系统，以选择性检查细胞外信号调节激酶1/2（ERK1 / 2）和Akt对基础JNK活性的调节。我们检测到激酶之间的复杂相互作用，以防止细胞死亡和神经突丢失。尤其是适当的JNK激活水平决定了细胞存活率。ERK1 / 2的基础活性减弱了JNK磷酸化的增强，从而诱导了细胞凋亡。重要的是，当JNK活性太低时，细胞活力和带有神经突的细胞数量也会减少，即使增强了ERK1 / 2的激活。在这种情况下，通过激活转录因子3（ATF3）抑制了JNK介导的生存信号。此外，由JNK抑制剂SP600125诱导的ERK1 / 2的磷酸化抑制了Akt的基础活性，该活性通常支持细胞活力。因此，控制JNK活性对于促进分化神经元细胞的存活和神经突稳定性至关重要。