hERG potassium channel blockage by scorpion toxin BmKKx2 enhances erythroid differentiation of human leukemia cells K562.
hERG potassium channel blockage by scorpion toxin BmKKx2 enhances erythroid differentiation of human leukemia cells K562.
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蝎毒素 BmKKx2 阻断 hERG 钾通道可增强人白血病细胞 K562 的红系分化
DOI：
10.1371/journal.pone.0084903
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Ma J;Hu Y;Guo M;Huang Z;Li W;Wu Y
hERG钾通道可调节慢性粒细胞白血病K562细胞的增殖，其在K562细胞向红系分化中的作用尚不清楚。新的36-残基蝎毒素BmKKx 2（一种有效的hERG通道阻断剂，IC 50为6.7±1.7 nM）阻断hERG钾通道，促进K562细胞的红系分化。K562细胞经毒素预处理24 h后，再经阿糖胞苷（Ara-C）处理72 h，其GPA（CD 235 a）荧光强度的平均值比单独Ara-C诱导的K562细胞高约2倍。hERG钾通道的这种独特作用也得到以下证据的支持：毒素BmKKx 2对细胞分化的作用在hERG缺陷细胞系中无效。在K562细胞分化过程中，BmKKx 2还能在mRNA和蛋白水平上抑制hERG通道的表达。在K562细胞分化过程中，BmKKx 2除了具有促分化作用外，还具有促进细胞凋亡的作用。此外，毒素BmKKx 2阻断hERG钾通道后，K562细胞分化过程中胞内Ca ~（2+）浓度降低，为hERG钾通道调控K562细胞分化过程的机制提供了新的思路。 结果表明蝎毒素BmKKx 2可通过抑制hERG钾通道电流促进白血病K562细胞向红系分化。这些发现不仅有助于促进hERG通道在不同白血病细胞中的功能研究，而且为天然蝎毒素作为抗白血病药物提供了前景。
The hERG potassium channel can modulate the proliferation of the chronic myelogenous leukemic K562 cells, and its role in the erythroid differentiation of K562 cells still remains unclear. The hERG potassium channel blockage by a new 36-residue scorpion toxin BmKKx2, a potent hERG channel blocker with IC50 of 6.7±1.7 nM, enhanced the erythroid differentiation of K562 cells. The mean values of GPA (CD235a) fluorescence intensity in the group of K562 cells pretreated by the toxin for 24 h and followed by cytosine arabinoside (Ara-C) treatment for 72 h were about 2-fold stronger than those of K562 cells induced by Ara-C alone. Such unique role of hERG potassium channel was also supported by the evidence that the effect of the toxin BmKKx2 on cell differentiation was nullified in hERG-deficient cell lines. During the K562 cell differentiation, BmKKx2 could also suppress the expression of hERG channels at both mRNA and protein levels. Besides the function of differentiation enhancement, BmKKx2 was also found to promote the differentiation-dependent apoptosis during the differentiation process of K562 cells. In addition, the blockage of hERG potassium channel by toxin BmKKx2 was able to decrease the intracellular Ca2+ concentration during the K562 cell differentiation, providing an insight into the mechanism of hERG potassium channel regulating this cellular process. Our results revealed scorpion toxin BmKKx2 could enhance the erythroid differentiation of leukemic K562 cells via inhibiting hERG potassium channel currents. These findings would not only accelerate the functional research of hERG channel in different leukemic cells, but also present the prospects of natural scorpion toxins as anti-leukemic drugs.
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DOI：
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发表时间：
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