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Autophagy; congenital long QT syndrome; endoplasmic reticulum stress; human ether-a`-go-gorelated gene

Congenital long QT syndrome (LQTS) is a heart channel disease associated with fatal ventricular arrhythmiasor cardiac arrest. Human ether-a-go-go-related gene (HERG) mutation is one of the main causes in type 2LQTS since it may lead to abundant immature HERG channel protein accumulate in the endoplasmic reticulum(ER). In our study, we have successfully constructed the G604S-HERG mutation in HEK293 cells anddemonstrated that the immature HERG protein on ER via Western blot and immunofluorescence. Herein wefound that unfolded protein reaction (UPR) process has been activated in order to counter this endoplasmicreticulum stress (ERS) since the main sensors got upregulated. Meanwhile, autophagy was also observed inthis process and verified by Western blot and transmission electron microscopy. To explore the relationshipunderlying autophagy and UPR in the condition of ERS, we found that PERK-EIF2-alpha-CHOP axis was activated.Our findings provides insight for G604S-HERG mutation in type 2 LQTS.

YUN ZHAO¹ SHUTING MA¹ MIAOMIAO CAO¹ CHAOFENG SUN¹

1. Department of Cardiovascular Medicine, Key Laboratory of Cardiovascular Channelopathy, The First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi 710061, China

Published

2 July 2020