(-)-Epicatechin rescues the As2O3-induced HERG K+ channel deficiency possibly through upregulating transcription factor SP1 expression
(-)-Epicatechin rescues the As2O3-induced HERG K+ channel deficiency possibly through upregulating transcription factor SP1 expression
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(-)-表儿茶素可能通过上调转录因子 SP1 表达来挽救 As2O3 诱导的 HERG K 通道缺陷
DOI：
10.1002/jbt.21966
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发表时间：
2017
影响因子：
3.6
通讯作者：
Li Baoxin
中科院分区：
文献类型：
--
作者：
Dong Zengxiang;Shi Yuanqi;Feng Lifang;Shen Zhaoqian;Fang Li;Zheng Sijia;Hai Xin;Li Baoxin
（−）-表儿茶素（EPI）对心血管疾病有有益的作用。人类ether-a-go-go-related gene（HERG）钾通道对心脏动作电位的复极至关重要。HERG通道的功能障碍可导致长QT综合征2型（LQT 2）。三氧化二砷（As 2 O3）已显示出治疗急性早幼粒细胞白血病的疗效。而As 2 O3则可导致HERG通道的缺失，导致LQT 2的发生。在这项研究中，我们研究了EPI是否可以挽救As 2 O3诱导的HERG通道缺陷。我们发现3 μM EPI明显增加HERG通道的蛋白表达和电流。EPI能恢复As 2 O3破坏的HERG通道的蛋白表达和电流。EPI能促进SP1蛋白的表达，并能恢复As 2 O3破坏的SP1蛋白的表达。此外，EPI显著缩短As_2O_3延长的动作电位时程。我们的数据表明，EPI通过上调SP1表达来挽救As 2 O3诱导的HERG通道缺陷。
(−)‐Epicatechin (EPI) has beneficial effects on the cardiovascular disease. The human ether‐a‐go‐go‐related gene (HERG) potassium channel is crucial for repolarization of cardiac action potential. Dysfunction of the HERG channel can cause long QT syndrome type 2 (LQT2). Arsenic trioxide (As2O3) has shown efficacy in the treatment of acute promyelocytic leukemia. However, As2O3can induce the deficiency of HERG channel and cause LQT2. In this study, we examined whether EPI could rescue the As2O3‐induced HERG channel deficiency. We found that 3 μM EPI obviously increased protein expression and current of HERG channel. EPI was able to recover the protein expression and current of HERG channel disrupted by As2O3. EPI was able to increase the expression of SP1 protein and recover the expression of SP1 protein disrupted by As2O3. In addition, EPI significantly shortened action potential duration prolonged by As2O3. Our data suggest that EPI rescues As2O3‐induced HERG channel deficiency through upregulating SP1 expression.