Role of gap junction-mediated intercellular communication on schaemia/reperfusion renal injury

连接蛋白形成通道调节细胞存活，关于其机制的信息很少。利用缺血性肾损伤模型，我们探讨了Cx43形成通道对肾细胞存活的潜在机制。我们的研究结果表明，Cx43影响细胞对缺血性肾损伤的易感性。Cx43水平高的细胞更容易受到缺血性氧化损伤。相反，Cx43水平低或无Cx43水平的细胞是耐药的。进一步的分析表明，氧化刺激激活Cx43半通道，导致细胞外ATP的损失。释放的ATP反过来通过嘌呤能受体介导的AKT和mTOR激活来抑制AMPK激活。抑制半通道增强AMPK活化，从而保护细胞免受氧化损伤。我们的研究表明，Cx43半通道决定细胞对氧化损伤的敏感性。以Cx43为靶点可用于缺血性肾损伤的防治。

Connexin-forming channels regulates cell survival with little information available regarding its mechanisms. Using a ischemic renal injury model, we explored the potential mechanisms of Cx43-forming channels on renal cell survival. Our results showed that Cx43 influenced cell susceptibility to ischemic renal injury. Cells with higher level of Cx43 were more vulnerable to ischemic oxidative injury. On the contrary, cells with no or lower level of Cx43 were resistant. Further analysis revealed that oxidative stimuli activated Cx43 hemichannels, leading to extracellular loss of ATP. The released ATP, in turn, suppressed AMPK activation through purinergistic receptor-mediated activation of AKT and mTOR. Suppression of hemichannels enhanced AMPK activation, thus protecting cells from oxidative injury. Our study indicates that Cx43 hemichannels determines cell susceptibility to oxidative injury. Targeting Cx43 could be developed for prevention and treatment of ischemic renal injury.