Lipopolysaccharides Up-regulate Kir6.1/SUR2B Channel Expression and Enhance Vascular KATP Channel Activity via NF-κB-dependent Signaling
Lipopolysaccharides Up-regulate Kir6.1/SUR2B Channel Expression and Enhance Vascular KATP Channel Activity via NF-κB-dependent Signaling
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DOI：
10.1074/jbc.m109.058313
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发表时间：
2010-01-29
影响因子：
4.8
通讯作者：
Jiang, Chun
中科院分区：
文献类型：
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作者：
Shi, Weiwei;Cui, Ningren;Jiang, Chun
脓毒症是一种严重的医学疾病，在世界范围内造成大量死亡。最近的研究表明，脓毒症的易感性是归因于血管ATP敏感性K+（K-ATP）通道。然而，脓毒症中通道调节的机制仍不清楚。在这里，我们显示了败血症病原体脂多糖（LPS）调节血管K-ATP通道的证据。在离体肠系膜动脉环中，苯肾上腺素（PE）产生浓度依赖性血管收缩，并被选择性K-ATP通道开放剂吡那地尔（pinacidil）舒张。用LPS处理破坏PE反应。在急性分离的主动脉平滑肌细胞中，LPS处理增强了K-ATP通道活性，并使细胞超极化。定量PCR分析表明，LPS以浓度依赖性方式提高Kir6.1和SUR 2B转录，这被转录抑制所抑制。一致地，相同的LPS处理不影响异源表达系统中的Kir6.1/SUR 2B通道。NF-κ B B抑制剂的存在消除了LPS对Kir6.1和SUR 2 B表达的影响。其他几种Toll样受体配体也刺激Kir6.1和SUR 2B表达，其程度与LPS相似。因此，LPS对血管舒张的作用涉及K-ATP通道表达的上调，其中NF-κ B依赖性信号传导起重要作用。
Sepsis is a severe medical condition causing a large number of deaths worldwide. Recent studies indicate that the septic susceptibility is attributable to the vascular ATP-sensitive K+ (K-ATP) channel. However, the mechanisms underlying the channel modulation in sepsis are still unclear. Here we show evidence for the modulation of vascular K-ATP channel by septic pathogen lipopolysaccharides (LPS). In isolated mesenteric arterial rings, phenylephrine (PE) produced concentration-dependent vasoconstriction that was relaxed by pinacidil, a selective K-ATP channel opener. The PE response was disrupted with a LPS treatment. In acutely dissociated aortic smooth myocytes the LPS treatment augmented K-ATP channel activity, and hyperpolarized the cells. Quantitative PCR analysis showed that LPS raised Kir6.1 and SUR2B transcripts in a concentration-dependent manner, which was suppressed by transcriptional inhibition. Consistently, the same LPS treatment did not affect Kir6.1/SUR2B channels in a heterologous expression system. The LPS effect on Kir6.1 and SUR2B expression was abolished in the presence of NF-kappa B inhibitors. Several other Toll-like receptor ligands also stimulated Kir6.1 and SUR2B expression to a similar degree as LPS. Thus, the effect of LPS on vasodilation involves up-regulation of K-ATP channel expression, in which the NF-kappa B-dependent signaling plays an important role.