Connexin43 hemichannel-mediated regulation of connexin43.
Connexin43 hemichannel-mediated regulation of connexin43.
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Connexin43 半通道介导的 connexin43 调节。
DOI：
10.1371/journal.pone.0058057
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yao J
中科院分区：
文献类型：
--
作者：
Li K;Chi Y;Gao K;Yan Q;Matsue H;Takeda M;Kitamura M;Yao J
许多调节间隙连接（GJs）蛋白表达和功能的信号分子和通路实际上也由GJs控制。因此，我们推测GJ通道介导的GJ自我调节的存在。通过镉（Cd2+）激活非连接连接蛋白43 （Cx43）半通道的细胞培养模型，我们验证了这一假设。用Cd2+孵育转染Cx43的LLC-PK1细胞导致Cx43的表达增加。Cd2+的这种作用与JNK的激活密切相关。JNK的抑制消除了Cx43的升高。进一步分析发现，JNK和Cx43的变化受GSH控制。补充具有膜渗透性的谷胱甘肽类似物谷胱甘肽乙酯或谷胱甘肽前体n -乙酰半胱氨酸可消除Cd2+对JNK活化和Cx43表达的影响。事实上，Cd2+诱导GSH的细胞外释放。用庚醇或Cx43模拟肽Gap26阻断Cx43半通道以阻止GSH外排可显著减弱Cd2+的Cx43升高作用。综上所述，我们的结果表明Cd2+诱导的Cx43的上调是通过激活非连接的Cx43半通道实现的。因此，我们的研究结果支持了半通道介导的Cx43自我调节的存在，并为Cx43表达和功能的分子机制提供了新的见解。
Many signaling molecules and pathways that regulate gap junctions (GJs) protein expression and function are, in fact, also controlled by GJs. We, therefore, speculated an existence of the GJ channel-mediated self-regulation of GJs. Using a cell culture model in which nonjunctional connexin43 (Cx43) hemichannels were activated by cadmium (Cd2+), we tested this hypothesis. Incubation of Cx43-transfected LLC-PK1 cells with Cd2+ led to an increased expression of Cx43. This effect of Cd2+ was tightly associated with JNK activation. Inhibition of JNK abolished the elevation of Cx43. Further analysis revealed that the changes of JNK and Cx43 were controlled by GSH. Supplement of a membrane-permeable GSH analogue GSH ethyl ester or GSH precursor N-acetyl-cystein abrogated the effects of Cd2+ on JNK activation and Cx43 expression. Indeed, Cd2+ induced extracellular release of GSH. Blockade of Cx43 hemichannels with heptanol or Cx43 mimetic peptide Gap26 to prevent the efflux of GSH significantly attenuated the Cx43-elevating effects of Cd2+. Collectively, our results thus indicate that Cd2+-induced upregulation of Cx43 is through activation of nonjunctional Cx43 hemichannels. Our findings thus support the existence of a hemichannel-mediated self-regulation of Cx43 and provide novel insights into the molecular mechanisms of Cx43 expression and function.
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影响因子：
2.3
作者：
Majoul, Irina V.;Onichtchouk, Daria;Duden, Rainer
通讯作者：
Duden, Rainer
影响因子：
3.3
作者：
Cherian, PP;Siller-Jackson, AJ;Jiang, JX
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Jiang, JX
影响因子：
2.4
作者：
Evans, W. Howard;Bultynck, Geert;Leybaert, Luc
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Leybaert, Luc
影响因子：
4.8
作者：
Oviedo-Orta, E;Gasque, P;Evans, WH
通讯作者：
Evans, WH
影响因子：
3.6
作者：
HEW, KW;HEATH, GL;WELSH, MJ
通讯作者：
WELSH, MJ