Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
Cell Mol Neurobiol. 2013 Oct;33(7):893-905. doi: 10.1007/s10571-013-9955-2. Epub 2013 Jul 14.
Nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcriptional factor, is involved in the control about the flow of genetic information and the modulation of diverse cellular activities. Accumulating evidence has demonstrated that NFATc4 exerted a pro-apoptotic effect in multiple diseases. Here, we explored the NFATc4's roles during the pathophysiological processes of intracerebral hemorrhage (ICH). An ICH rat model was built and evaluated according to behavioral testing. Using Western blot, immunohistochemistry, and immunofluorescence, significant up-regulation of NFATc4 was found in neurons in brain areas surrounding the hematoma following ICH. Increasing NFATc4 expression was found to be accompanied by the up-regulation of Fas ligand (FasL), active caspase-8, and active caspase-3, respectively. Besides, NFATc4 co-localized with active caspase-3 in neurons, indicating its role in neuronal apoptosis. Our in vitro study, using NFATc4 RNA interference in PC12 cells, further confirmed that NFATc4 might exert its pro-apoptotic function in neuronal apoptosis through extrinsic pathway. Thus, NFATc4 may play a role in promoting the brain secondary damage following ICH.
核因子活化 T 细胞的细胞质 4（NFATc4）是一种转录因子，参与控制遗传信息的流动和多种细胞活动的调节。越来越多的证据表明，NFATc4 在多种疾病中发挥促凋亡作用。在这里，我们探讨了 NFATc4 在脑出血（ICH）病理生理过程中的作用。根据行为测试，建立和评估了 ICH 大鼠模型。通过 Western blot、免疫组织化学和免疫荧光，发现 NFATc4 在 ICH 后血肿周围脑区的神经元中显著上调。发现 NFATc4 表达增加伴随着 Fas 配体（FasL）、活性半胱天冬酶-8 和活性半胱天冬酶-3 的上调。此外，NFATc4 与神经元中的活性半胱天冬酶-3 共定位，表明其在神经元凋亡中的作用。我们在 PC12 细胞中使用 NFATc4 RNA 干扰的体外研究进一步证实，NFATc4 可能通过外在途径在神经元凋亡中发挥促凋亡作用。因此，NFATc4 可能在促进 ICH 后的脑继发性损伤中发挥作用。
