Kawamura Kenji, Kano Yoshio
Graduate School of Health Science, Kibi International University, 8 Iga-machi, Takahashi City, Okayama, 716-8508, Japan.
Graduate School of Health Science, Kibi International University, 8 Iga-machi, Takahashi City, Okayama, 716-8508, Japan.
Neurosci Lett. 2019 Apr 17;698:81-84. doi: 10.1016/j.neulet.2019.01.015. Epub 2019 Jan 8.
We investigated the role of the p38 mitogen-activated protein kinase (MAPK) pathway in electrical stimulation-induced neurite outgrowth of PC12 mutant cells in which nerve growth factor (NGF)-induced neurite outgrowth is impaired. When cultures of the PC12 mutant (PC12m3) cells were exposed to electrical stimulation at 100 mA for 30 min, activity of p38 MAPK increased and neurite outgrowth was greatly enhanced. The frequency of neurite outgrowth induced by electrical stimulation was approximately 10-fold greater than that of neurite outgrowth induced by NGF alone. The neurite outgrowth induced by electrical stimulation was inhibited by a specific p38 MAPK inhibitor, SB203580. The activation of p38 MAPK induces activation of the transcription factor CREB. The activation of CREB induced by electrical stimulation was inhibited by SB203580. Longer electrical stimulation of PC12m3 cells provoked cell death, which was enhanced by SB203580. These findings suggest that electrical stimulation-induced activation of the p38 MAPK/CREB pathway is responsible for the neurite outgrowth and survival of PC12m3 cells.
我们研究了p38丝裂原活化蛋白激酶（MAPK）通路在神经生长因子（NGF）诱导的神经突生长受损的PC12突变细胞电刺激诱导的神经突生长中的作用。当PC12突变体（PC12m3）细胞培养物在100 mA下接受30分钟的电刺激时，p38 MAPK的活性增加，神经突生长大大增强。电刺激诱导的神经突生长频率比单独NGF诱导的神经突生长频率大约高10倍。电刺激诱导的神经突生长被特异性p38 MAPK抑制剂SB203580抑制。p38 MAPK的激活诱导转录因子CREB的激活。电刺激诱导的CREB激活被SB203580抑制。对PC12m3细胞进行更长时间的电刺激会引发细胞死亡，而SB203580会增强这种细胞死亡。这些发现表明，电刺激诱导的p38 MAPK/CREB通路激活负责PC12m3细胞的神经突生长和存活。
