Inhibition of cytokine-induced connexin43 hemichannel activity in astrocytes is neuroprotective
Inhibition of cytokine-induced connexin43 hemichannel activity in astrocytes is neuroprotective
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DOI：
10.1016/j.mcn.2010.05.007
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Giaume, Christian
中科院分区：
文献类型：
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作者：
Froger, Nicolas;Orellana, Juan A.;Giaume, Christian
星形胶质细胞表达高水平的连接蛋白43，这种蛋白形成两种通道：用于直接细胞间通信的间隙连接通道和用于与细胞外空间交换的半通道。炎症诱导连接蛋白43半通道激活，这被认为与神经胶质相互作用有关。在这里，我们研究了连接蛋白43在神经元/星形胶质细胞共培养中对nmda诱导的兴奋性毒性的贡献，在用含有tnf - α和il - 1- β (Mix)的促炎细胞因子混合物处理后，刺激星形胶质连接蛋白43半通道活性。有趣的是，NMDA处理在混合处理的共培养物中诱导的神经毒性比未处理的高，而在富集的神经元培养物或与connexin43敲除的星形胶质细胞共培养物中没有这种程度的神经毒性。此外，应用connexin43半通道阻滞剂或合成大麻素可防止mix诱导的增强NMDA神经毒性。总之，这些数据表明炎症诱导的星形胶质半通道激活在神经元死亡中起关键作用，并提示连接蛋白43半通道阻断具有神经保护作用。(C) 2010爱思唯尔公司版权所有。
Astrocytes express high levels of connexin43, a protein that forms two types of channels: gap junction channels for direct intercellular communication, and hemichannels for exchanges with the extracellular space. Inflammation induces connexin43 hemichannel activation, which has been proposed to be involved in neuroglial interactions. Here, we investigated the contribution of connexin43 to NMDA-induced excitotoxicity in neuron/astrocyte cocultures, after treatment with a pro-inflammatory cytokine mixture, containing TNF-alpha and IL1-beta (Mix), that stimulated astroglial connexin43 hemichannel activity. Interestingly, NMDA treatment induced a higher amount of neurotoxicity in Mix-treated co-cultures than in untreated ones, whereas this extent of neurotoxicity was absent in enriched neuron cultures or in co-cultures with connexin43 knock-out astrocytes. Furthemore, application of connexin43 hemichannel blockers or a synthetic cannabinoid prevented the Mix-induced potentiated NMDA neurotoxicity. Altogether, these data demonstrate that inflammation-induced astroglial hemichannel activation plays a critical role in neuronal death and suggest a neuroprotective role of connexin43 hemichannel blockade. (C) 2010 Elsevier Inc. All rights reserved.