Electrical stimulation induces neurite outgrowth in PC12m3 cells via the p38 mitogen-activated protein kinase pathway
Electrical stimulation induces neurite outgrowth in PC12m3 cells via the p38 mitogen-activated protein kinase pathway
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DOI：
10.1016/j.neulet.2019.01.015
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发表时间：
2019-04-17
影响因子：
2.5
通讯作者：
Kano, Yoshio
中科院分区：
文献类型：
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作者：
Kawamura, Kenji;Kano, Yoshio
我们研究了p38丝裂原激活蛋白激酶（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。当培养的PC12突变体（PC12m3）细胞在100 mA的电刺激下暴露30分钟时，p38 MAPK的活性增加，神经突起的生长大大增强。电刺激诱导的神经突生长频率比单纯NGF诱导的神经突生长频率高约10倍。特定的p38 MAPK抑制剂SB203580可以抑制电刺激诱导的神经突生长。p38 MAPK的激活诱导了转录因子CREB的激活。电刺激诱导的CREB活化被SB203580抑制。长时间电刺激PC12m3细胞可引起细胞死亡，SB203580可增强细胞死亡。这些发现表明，电刺激诱导的p38 MAPK/CREB通路的激活是PC12m3细胞神经突生长和存活的原因。
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.