Pannexins in ischemia-induced neurodegeneration
Pannexins in ischemia-induced neurodegeneration
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DOI：
10.1073/pnas.1018262108
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发表时间：
2011-12-20
影响因子：
11.1
通讯作者：
Schwaninger, Markus
中科院分区：
文献类型：
--
作者：
Bargiotas, Panagiotis;Krenz, Antje;Schwaninger, Markus
泛连接蛋白1（Px 1，Panx 1）和泛连接蛋白2（Px 2，Panx 2）在细胞质膜上形成大孔非选择性通道，并被认为在脑缺血的病理生理中发挥作用。为了直接测试泛连接蛋白在缺血相关机制中的潜在贡献，我们在Px 1（-/-）、Px 2（-/-）和Px 1（-/-）Px 2（-/-）敲除小鼠中进行了实验。在Px 1（-/-）Px 2（-/-）小鼠中，IL-1 β释放、星形胶质细胞中的通道功能和皮质扩散去极化没有改变，这表明与先前的概念相反，这些过程在没有泛连接蛋白通道的情况下正常发生。然而，缺血诱导的皮层神经元染料释放较低，表明Px 1（-/-）Px 2（-/-）神经元的通道功能受损。此外，Px 1（-/-）Px 2（-/-）小鼠在缺血性中风时比野生型小鼠具有更好的功能结局和更小的梗死。总之，我们的数据表明，Px 1和Px 2是神经元通道功能的基础，并有助于缺血性脑损伤。
Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed experiments in Px1(-/-), Px2(-/-), and Px1(-/-) Px2(-/-) knockout mice. IL-1 beta release, channel function in astrocytes, and cortical spreading depolarization were not altered in Px1(-/-) Px2(-/-) mice, indicating that, in contrast to previous concepts, these processes occur normally in the absence of pannexin channels. However, ischemia-induced dye release from cortical neurons was lower, indicating that channel function in Px1(-/-) Px2(-/-) neurons was impaired. Furthermore, Px1(-/-) Px2(-/-) mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. In conclusion, our data demonstrate that Px1 and Px2 underlie channel function in neurons and contribute to ischemic brain damage.