Na,K-ATPase as a signal transducer
Na,K-ATPase as a signal transducer
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DOI：
10.1111/j.1749-6632.2003.tb07233.x
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Aperia, A
中科院分区：
文献类型：
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作者：
Aizman, O;Aperia, A
最近的研究表明，Na，K-ATPase除了是细胞内Na+和K+浓度的关键调节器外，还可能充当信号转导器。尽管进行了广泛的研究，哇巴因，Na，K-ATP酶的天然配体的生物学作用还没有得到很好的理解。我们已经报道，大鼠近端肾小管细胞（RPTC）暴露于抑制Na，K-ATP酶活性低于50%（10 nM-500 μ M）的哇巴因剂量，将诱导细胞内[Ca 2 +]（i）振荡，这种钙信号导致转录因子NF-κ B的激活。哇巴因诱导的钙振荡被IP 3受体的抑制剂阻断，但不是由磷脂酶C抑制剂，也不是由IP 3的细胞耗竭，这表明钙信号不是由于磷脂酶C介导的IP 3释放。荧光共振能量转移（FRET）研究表明，Na，K-ATP酶和IP 3受体之间的紧密联系。我们的研究结果证明了一个新的原则，钙信号通过Na，K-ATP酶。
Recent studies have indicated that Na,K-ATPase may, in addition to being the key regulator of intracellular Na+ and K+ concentration, act as a signal transducer. Despite extensive research, the biological role for ouabain, a natural ligand of Na,K-ATPase, is not well understood. We have reported that exposure of rat proximal tubular cells (RPTC) to doses of ouabain that inhibit the Na,K-ATPase activity by less than 50% (10 nM-500 muM), will induce intracellular [Ca2+](i), oscillations and that this calcium signal leads to activation of the transcription factor NF-kappaB. The ouabain-induced calcium oscillations were blocked by an inhibitor of the IP3 receptors but not by phospholipase C inhibitors nor by cellular depletion of IP3, suggesting that the calcium signal is not due to phospholipase C-mediated IP3 release. Fluorescence resonance energy transfer (FRET) studies suggested a close proximity between the Na,K-ATPase and IP3 receptor. Our findings demonstrate a novel principle for calcium signaling via Na,K-ATPase.