Activation of the phospholipase C signaling pathway in nerve growth factor-treated neurons by carbon nanotubes.
Activation of the phospholipase C signaling pathway in nerve growth factor-treated neurons by carbon nanotubes.
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DOI：
10.1016/j.biomaterials.2013.04.038
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发表时间：
2013-08
期刊：
影响因子：
14
通讯作者：
Kotaro Matsumoto;N. Shimizu
中科院分区：
文献类型：
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作者：
Kotaro Matsumoto;N. Shimizu
低浓度的碳纳米管(CNTs)通过激活细胞外信号调节激酶(ERK)促进神经生长因子(NGF)处理的神经元突起生长，即使在神经元培养液中加入MEK抑制剂时也是如此。我们推测，CNTs可能通过磷脂酶C(PLC)信号通路激活ERK，而不依赖于ERK信号通路中的Ras/Raf/MEK级联信号通路。碳纳米管可促进神经生长因子处理的神经元中PLC-γ1的磷酸化，但不能增加神经生长因子处理的神经元突起的数目和长度。此外，CNTs+NGF处理的细胞内钙离子水平高于单独NGF处理的细胞。尽管CNTs和NGF联合应用可增加MEK抑制剂处理的神经元中磷酸化ERK(p-ERK)的浓度，但CNTs不能诱导PLC抑制剂处理的神经元中ERK的磷酸化。这些数据表明，PLC信号通路中的PKC可能独立于Ras/Raf/MEK级联激活ERK。综上所述，我们确定了PLC信号在神经生长因子处理的神经元在碳纳米管存在下的轴突生长中的作用。
Low concentrations of carbon nanotubes (CNTs) promoted the number of nerve growth factor (NGF)-treated neurons with neurite outgrowth by activating extracellular signal-regulated kinase (ERK), even when MEK inhibitor was added to the neuron culture medium. We speculated that CNTs may activate ERK through the phospholipase C (PLC) signaling pathway independent of the Ras/Raf/MEK cascade involved in the ERK signaling pathway. CNTs enhanced phosphorylation of PLC-γ1 in NGF-treated neurons but failed to increase the number and length of neurites of NGF-treated neurons with neurite outgrowth when a PLC inhibitor, an inositol triphosphate receptor (IP3R) inhibitor, or an inhibitor of protein kinase C (PKC) in the PLC signaling pathway were added to the neuron culture medium. Furthermore, intracellular Ca++levels of cells treated with CNTs+NGF were higher than those of cells treated with NGF alone. Although the combination of CNTs and NGF increased the concentration of phosphorylated ERK (p-ERK) in MEK inhibitor-treated neurons, CNTs did not induce phosphorylation of ERK in PLC inhibitor-treated neurons. These data suggest that PKC in the PLC signaling pathway may activate ERK independent of the Ras/Raf/MEK cascade. In summary, we identified a role of PLC signaling in mediating neurite outgrowth of NGF-treated neurons in the presence of CNTs.