有毒蘑菇提取物对人类醚-α--go-go 相关基因通道表达和功能的新作用。
Novel effects of extracts from poisonous mushrooms on expression and function of the human ether-a-go-go-related gene channel.
机构信息
Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Japan.
出版信息
Biol Pharm Bull. 2011;34(9):1474-80. doi: 10.1248/bpb.34.1474.
UNLABELLED
The human ether-a-go-go-related gene (hERG) encodes the α subunit of the potassium current I(Kr), which plays a pivotal role in cardiac action potential repolarization. Inherited mutations of this gene cause Long QT syndrome type 2. hERG expression is altered by several types of drugs as well as by temperature. Heat shock protein 70 (Hsp70) and Heat shock cognate protein 70 (Hsc70) have reciprocal effects on hERG proteins. We examined the effects of poisonous mushrooms on hERG protein expression and its channel function.
METHODS
We evaluated the effects of several types of poisonous mushrooms on the expression and function of wild-type hERG by Western blotting, reverse transcription polymerase chain reaction (PCR), and patch clamping in transfected HEK293 cells and mouse HL-1 cardiomyocytes.
RESULTS
Extracts of Gymnopilus junonius (junonius) increased expression of both hERG and Hsp70 in HEK293 cells with concomitant decrease in Hsc70, whereas extracts of Amanita ibotengutake (ibotengutake) decreased hERG proteins with increase in Hsc70. Knockdown of Hsp70 and Hsc70 by small interfering RNA abolished the effects of the two mushrooms on hERG, respectively. Certain fractions of junonius increased expression of hERG proteins. hERG currents were increased by extracts of junonius, resulting in shortening of action potential duration (APD). In contrast, hERG currents were decreased and APD was prolonged by extracts of ibotengutake.
CONCLUSION
junonius enhanced the expression and function of hERG by increasing Hsp70 and decreasing Hsc70. Ibotengutake decreased hERG expression via increase in Hsc70. Constituents of junonius may have the potential for use in treatment of arrhythmia.
未加标签
人醚-α-go-go 相关基因（hERG）编码钾电流 I（Kr）的 α 亚基，该电流在心脏动作电位复极化中起着关键作用。该基因的遗传突变导致 2 型长 QT 综合征。几种类型的药物以及温度都会改变 hERG 的表达。热休克蛋白 70（Hsp70）和热休克同源蛋白 70（Hsc70）对 hERG 蛋白有相互影响。我们研究了毒蕈对 hERG 蛋白表达及其通道功能的影响。
方法
我们通过 Western blot、逆转录聚合酶链反应（PCR）和转染 HEK293 细胞和小鼠 HL-1 心肌细胞中的膜片钳技术评估了几种毒蕈对野生型 hERG 表达和功能的影响。
结果
Gymnopilus junonius（junonius）提取物增加了 HEK293 细胞中 hERG 和 Hsp70 的表达，同时减少了 Hsc70，而 Amanita ibotengutake（ibotengutake）提取物则减少了 hERG 蛋白，增加了 Hsc70。用小干扰 RNA 敲低 Hsp70 和 Hsc70 分别消除了两种蕈类对 hERG 的影响。junonius 的某些馏分增加了 hERG 蛋白的表达。junonius 提取物增加了 hERG 电流，导致动作电位时程（APD）缩短。相比之下，ibotengutake 提取物减少了 hERG 电流并延长了 APD。
结论
junonius 通过增加 Hsp70 和减少 Hsc70 来增强 hERG 的表达和功能。ibotengutake 通过增加 Hsc70 减少 hERG 表达。junonius 的成分可能具有治疗心律失常的潜力。
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