Bi-directionally protective communication between neurons and astrocytes under ischemia.

Bi-directionally protective communication between neurons and astrocytes under ischemia.
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缺血下神经元和星形胶质细胞之间的双向保护性通讯

DOI:
10.1016/j.redox.2017.05.010
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发表时间:
2017-10
期刊:
影响因子:
11.4
通讯作者:
Ke Y
Ke Y
中科院分区:
生物学1区
文献类型:
--
作者:
Wu XM;Qian C;Zhou YF;Yan YC;Luo QQ;Yung WH;Zhang FL;Jiang LR;Qian ZM;Ke Y

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关于星形胶质细胞和神经元之间双向通信的广泛现有知识使我们推测,不仅缺血预处理(IP)星形胶质细胞可以保护神经元,而且IP神经元也可以保护星形胶质细胞免受致命的缺血性损伤。在这里,我们首次证明神经元在保护星形胶质细胞免受缺血性损伤方面具有重要作用。 IP 神经元 (IPcNCM) 的培养液在体外诱导缺血性星形胶质细胞中 LDH 的显着减少和细胞活力的增加。红藻氨酸注射选择性神经元损失诱导体内缺血大鼠脑中凋亡星形胶质细胞数量显着增加。此外,TUNEL 分析、DNAladder 测定以及体外和/或体内 ROS、GSH、促凋亡因子和抗凋亡因子、抗氧化酶和信号分子的测量表明,IP 神经元通过 EPO 介导的促凋亡信号抑制、通过 P13K/ERK/STAT5 途径激活抗凋亡蛋白以及通过上调抗氧化酶激活抗氧化蛋白来保护星形胶质细胞。我们证明了缺血下 IP 神经元存在天体保护作用,并提出细胞之间的双向保护通讯可能是大多数(如果不是全部)病理条件下大脑或外周器官的常见活动。
The extensive existing knowledge on bi-directional communication between astrocytes and neurons led us to hypothesize that not only ischemia-preconditioned (IP) astrocytes can protect neurons but also IP neurons protect astrocytes from lethal ischemic injury. Here, we demonstrated for the first time that neurons have a significant role in protecting astrocytes from ischemic injury. The cultured medium from IP neurons (IPcNCM) induced a remarkable reduction in LDH and an increase in cell viability in ischemic astrocytes in vitro. Selective neuronal loss by kainic acid injection induced a significant increase in apoptotic astrocyte numbers in the brain of ischemic rats in vivo. Furthermore, TUNEL analysis, DNA ladder assay, and the measurements of ROS, GSH, pro- and anti-apoptotic factors, anti-oxidant enzymes and signal molecules in vitro and/or in vivo demonstrated that IP neurons protect astrocytes by an EPO-mediated inhibition of pro-apoptotic signals, activation of anti-apoptotic proteins via the P13K/ERK/STAT5 pathways and activation of anti-oxidant proteins via up-regulation of anti-oxidant enzymes. We demonstrated the existence of astro-protection by IP neurons under ischemia and proposed that the bi-directionally protective communications between cells might be a common activity in the brain or peripheral organs under most if not all pathological conditions.