Premium
(−)‐Epicatechin rescues the As 2 O 3 ‐induced HERG K + channel deficiency possibly through upregulating transcription factor SP1 expression
Author(s) -
Dong Zengxiang,
Shi Yuanqi,
Feng Lifang,
Shen Zhaoqian,
Fang Li,
Zheng Sijia,
Hai Xin,
Li Baoxin
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21966
Subject(s) - herg , potassium channel , arsenic trioxide , chemistry , repolarization , acute promyelocytic leukemia , pharmacology , transcription factor , long qt syndrome , medicine , endocrinology , biology , biochemistry , gene , electrophysiology , qt interval , apoptosis , retinoic acid
(−)‐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 (As 2 O 3 ) has shown efficacy in the treatment of acute promyelocytic leukemia. However, As 2 O 3 can induce the deficiency of HERG channel and cause LQT2. In this study, we examined whether EPI could rescue the As 2 O 3 ‐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 As 2 O 3 . EPI was able to increase the expression of SP1 protein and recover the expression of SP1 protein disrupted by As 2 O 3 . In addition, EPI significantly shortened action potential duration prolonged by As 2 O 3 . Our data suggest that EPI rescues As 2 O 3 ‐induced HERG channel deficiency through upregulating SP1 expression.