Nerve growth factor modulates the activation status and fast axonal transport of ERK 1/2 in adult nociceptive neurones

Nerve growth factor modulates the activation status and fast axonal transport of ERK 1/2 in adult nociceptive neurones
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DOI:
10.1006/mcne.2001.1015
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发表时间:
2001-08-01
影响因子:
3.5
通讯作者:
Priestley, JV
Priestley, JV
中科院分区:
医学3区
文献类型:
--
作者:
Averill, S;Delcroix, JD;Priestley, JV

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成熟的背根神经节细胞对神经营养因子有反应,神经营养因子激活的细胞内信号通路已经在体外得到了表征。我们现在用免疫细胞化学和免疫印迹法检测了细胞外信号调节蛋白激酶-1/2(ERK)在大鼠背根神经节细胞中的表达和激活,使用了总(Terk)和磷酸化(Perk)形式的抗血清。这揭示了一些新的发现。TERK免疫反应存在于大多数背根神经节细胞中,但在小(伤害性)细胞中表达最强,令人惊讶的是,在表达TrkB或trkC但主要缺乏p75(NTR)免疫反应的大细胞中不存在TERK。相比之下,PERK在少数TrkA细胞和卫星神经胶质细胞中显著增加,并且经NGF处理后进一步增加。Terk和PERK都经历了快速的顺行和逆行轴突运输,如坐骨神经结扎处的积聚所示,而NGF降低了PERK逆行运输的水平。
Mature dorsal root ganglion cells respond to neurotrophins, and the intracellular signalling pathways activated by neurotrophins have been characterized in vitro. We have now used immunocytochemistry and Western blots to examine the expression and activation of extracellular signal-regulated protein kinase-1/2 (ERK) in rat dorsal root ganglion cells in vivo, using antisera to total (tERK) and phosphorylated (pERK) forms. This has revealed a number of novel findings. tERK immunoreactivity is present in most dorsal root ganglion cells but is expressed most strongly in small (nociceptive) cells and, surprisingly, is absent in a population of large cells that expressed trkB or trkC but mainly lack p75(NTR) immunoreactivity. In contrast pERK is prominent in a few trkA cells and in satellite glial cells, and is further increased by NGF treatment. tERK and pERK both undergo fast anterograde and retrograde axonal transport, indicated by accumulation at a sciatic nerve ligature, and NGF reduces the level of retrograde pERK transport.