Quercetin is a foe in the heart by targeting the hERG potassium channel
- سال انتشار: 1403
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 27، شماره: 11
- کد COI اختصاصی: JR_IJBMS-27-11_006
- زبان مقاله: انگلیسی
- تعداد مشاهده: 122
نویسندگان
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
Department of Pharmacy, Jiangsu Province Official Hospital
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
چکیده
Objective(s): Quercetin is a plant flavonoid known for its pharmacological activities, such as antioxidant, anti-inflammatory, and anti-cancer properties. However, there is limited information available regarding its potential toxicities. A previous study showed that quercetin can inhibit human ether-a-go-related gene (hERG, also named KCNH۲) currents, which may lead to long QT syndrome, torsade de pointes (TdP), and even sudden cardiac death. This study aimed to investigate the effects of quercetin on hERG and its potential mechanism.Materials and Methods: hERG currents and action potential duration (APD) were assessed using the patch clamp technique. Molecular docking was employed to elucidate the binding sites between quercetin and hERG. Transfection of wild-type or mutant plasmids was used to verify the results of molecular docking. Western blot was performed to determine the expression levels of hERG, transcription factor SP۱, molecular chaperones HSP۷۰ and HSP۹۰, phosphorylated E۳ ubiquitin ligase p-Nedd۴-۲, serum- and glucocorticoid-inducible kinase (SGK۱), and phosphatidylinositol ۳-kinase (PI۳K). Immunoprecipitation was conducted to evaluate hERG ubiquitination.Results: Quercetin acutely blocked hERG current by binding to F۶۵۶ amino acid residue, subsequently accelerating channel inactivation. Long-term incubation of quercetin accelerates Nedd۴-۲-mediated ubiquitination degradation of hERG channels by inhibiting the PI۳K/SGK۱ signaling pathway. Moreover, the APD of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) is significantly prolonged by ۳۰ μM quercetin.Conclusion: Quercetin has a potential risk of proarrhythmia, which provided useful information for the usage and development of quercetin as a medication.کلیدواژه ها
Degradation, KCNH۲, Long QT syndrome, Nedd۴, Ubiquitinationاطلاعات بیشتر در مورد COI
COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.
کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.