Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue
Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue
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DOI：
10.1016/j.brainresrev.2004.08.002
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Sáez, JC
中科院分区：
文献类型：
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作者：
Contreras, JE;Sánchez, HA;Sáez, JC
间隙连接通道和连接蛋白亚基形成的半通道存在于脊椎动物的大多数细胞类型中。间隙连接通过不向细胞外空间开放的通道连接细胞，并允许类似于1 kDa的离子和分子通过。单个连接蛋白半通道，其为连接蛋白六聚体，在与并置膜中的半通道对接之前存在于表面膜中。由于它们在细胞-细胞通道中的高传导性和渗透性，人们一直认为连接蛋白半通道保持关闭，直到对接形成细胞-细胞通道。现在很清楚，至少有一些半通道可以打开，允许细胞质和细胞外空间之间的分子通过。在这里，我们审查的证据表明，间隙连接通道可能允许坏死或凋亡信号的细胞间扩散，但也可能允许离子和物质从健康细胞扩散到受损细胞，从而有助于细胞存活。此外，缝隙连接半通道的开放可能加剧细胞损伤或介导旁分泌或自分泌信号传导。除了缺血性损伤的细胞特异性特征之外，受影响组织内细胞损伤和死亡的传播可能受到由连接蛋白形成的间隙连接通道和半通道的表达和调节的影响。(C)2004 Elsevier B.V保留所有权利。
Gap junction channels and hemichannels formed of connexin subunits are found in most cell types in vertebrates. Gap junctions connect cells via channels not open to the extracellular space and permit the passage of ions and molecules of similar to 1 kDa. Single connexin hemichannels, which are connexin hexamers, are present in the surface membrane before docking with a hemichannel in an apposed membrane. Because of their high conductance and permeability in cell-cell channels, it had been thought that connexin hemichannels remained closed until docking to form a cell-cell channel. Now it is clear that at least some hemichannels can open to allow passage of molecules between the cytoplasm and extracellular space. Here we review evidence that gap junction channels may allow intercellular diffusion of necrotic or apoptotic signals, but may also allow diffusion of ions and substances from healthy to injured cells, thereby contributing to cell survival. Moreover, opening of gap junction hemichannels may exacerbate cell injury or mediate paracrine or autocrine signaling. In addition to the cell specific features of an ischemic insult, propagation of cell damage and death within affected tissues may be affected by expression and regulation of gap junction channels and hemichannels formed by connexins. (C) 2004 Elsevier B.V All rights reserved.