Novel Effects of Extracts from Poisonous Mushrooms on Expression and Function of the Human ether-a-go-go-Related Gene Channel
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概要
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The human ether-a-go-go-related gene (hERG) encodes the α subunit of the potassium current IKr, 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.
著者
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Hisatome Ichiro
Division Of Molecular Medicine And Therapeutics Department Of Multidisciplinary Internal Medicine To
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Shirayoshi Yasuaki
Division Of Regenerative Medicine And Therapeutics Department Of Genetic Medicine And Regenerative T
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Li Peili
Division of Molecular Medicine and Therapeutics, Tottori University
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Ninomiya Haruaki
Department Of Biological Regulation Faculty Of Medicine Tottori University
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Utami Sulistiyati-Bayu
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
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Shirayoshi Yasuaki
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
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Li Peili
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
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Hisatome Ichiro
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
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Tanaka Saki
School of Agricultural, Biological and Environmental Sciences, Tadanori Aimi Faculty of Agriculture, Tottori University
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Ichiyanagi Tsuyoshi
School of Agricultural, Biological and Environmental Sciences, Tadanori Aimi Faculty of Agriculture, Tottori University
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Ting Yakuang
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
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Aimi Tadanori
School of Agricultural, Biological and Environmental Sciences, Tadanori Aimi Faculty of Agriculture, Tottori University
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Miake Junichiro
Faculty of Medicine, Tottori University
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Ninomiya Haruaki
Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University
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Hisatome Ichiro
Division of Cardiovascular Medicine, Department of Internal Medicine, Tottori University Faculty of Medicine
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