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Involvement of MAPK, Akt/GSK-3β and AMPK/mTOR signaling pathways in protection of remote glial cells from axotomy-induced necrosis and apoptosis in the isolated crayfish stretch receptor.
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2017-06-24 , DOI: 10.1016/j.mcn.2017.06.003
E V Berezhnaya 1 , M Y Bibov 1 , M A Komandirov 1 , M A Neginskaya 1 , M V Rudkovskii 1 , A B Uzdensky 1
Affiliation  

Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells. After axon transection, stretch receptors were isolated and incubated in saline in the presence or without specific inhibitors of various signaling proteins. Inhibition of MEK1/2, p38, Akt, GSK-3β and mTOR increased axotomy-induced apoptosis of remote glial cells, whereas inhibition of ERK1/2 and GSK-3β enhanced necrosis. This suggests the involvement of these signaling proteins in protective, antiapoptotic and antinecrotic processes in the remote satellite glia surrounding the axotomized mechanoreceptor neuron.

中文翻译:

MAPK,Akt /GSK-3β和AMPK / mTOR信号通路参与保护远端神经胶质细胞免受轴突切开术引起的坏死和分离的小龙虾拉伸受体凋亡的影响。

严重的机械神经损伤(如轴切术)可能导致神经元变性和周围神经胶质细胞死亡。我们显示,轴切术不仅在切割位置机械损伤神经胶质细胞,而且还诱导远离横切部位的卫星神经胶质细胞坏死或凋亡。因此,轴突完整性对于周围神经胶质细胞的生存是必需的。在研究各种信号蛋白在轴突切开引起的远端神经胶质细胞死亡中的作用时,我们将小龙虾牵张受体(由单个神经胶质细胞覆盖的单个机械感受器神经元组成)用作简单但可提供信息的模型对象。轴突横断后,分离拉伸受体并在存在或不存在各种信号蛋白特异性抑制剂的情况下在盐水中孵育。抑制MEK1 / 2,p38,Akt,GSK-3β和mTOR增加了轴突切开术诱导的远端神经胶质细胞的凋亡,而ERK1 / 2和GSK-3β的抑制作用增强了坏死。这表明这些信号蛋白参与了轴突切除的机械感受器神经元周围的远端卫星神经胶质细胞的保护,抗凋亡和抗坏死过程。
更新日期:2019-11-01
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