Vascular pharmacology · 2026
Spermidine ameliorates BK channel dysfunction in diabetic coronary smooth muscle cells via PKM2/STAT3/FBXO32 axis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Zhen-Ye, Zhou Jia-Bin, Yang Ya-Juan, Zhao Shan-Ying, Fan Si-Yu, Pan Lu, Shen Jun-Xian, Wang Chao, Shao Yang-Ge, Zheng Jie, Qian Ling-Ling, Dang Shipeng, Wang Ru-Xing
Аннотация
BACKGROUND: Spermidine (SPD) exhibits potential protective effects against diabetic-induced BK channel dysfunction, though the molecular mechanisms remain unclear. This study investigated SPD-mediated regulation of large-conductance calcium- and voltage-activated potassium channel (BK channel) function in coronary smooth muscle cells (SMCs) and the underlying molecular pathways.
METHODS: Rats were randomly divided into: control (Ctrl), diabetes mellitus (DM), and DM with SPD treatment (DM + SPD) groups. Vascular function was assessed using coronary artery tension measurements, while BK channel activity was evaluated via whole-cell patch clamp. Primary vascular SMCs were isolated for in vitro studies. SPD-binding proteins were identified through pull-down assays coupled with LC-MS/MS analysis.
RESULTS: SPD treatment improved coronary BK channel-dependent vasorelaxation by up-regulating BK-β1 subunit expression. Mechanistically, SPD directly bound to pyruvate kinase M2 (PKM2), inhibiting PKM2 nuclear translocation and subsequent signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, STAT3 transcriptionally regulated F-box protein 32 (FBXO32), which modulated BK-β1 expression.
CONCLUSIONS: SPD protects BK channel function in diabetic conditions through inhibition of the PKM2/STAT3 signaling axis, revealing a novel therapeutic pathway for diabetic vascular complications. However, given the exploratory experimental nature of this study, these findings should be considered hypothesis-generating and require further validation in independent studies.
METHODS: Rats were randomly divided into: control (Ctrl), diabetes mellitus (DM), and DM with SPD treatment (DM + SPD) groups. Vascular function was assessed using coronary artery tension measurements, while BK channel activity was evaluated via whole-cell patch clamp. Primary vascular SMCs were isolated for in vitro studies. SPD-binding proteins were identified through pull-down assays coupled with LC-MS/MS analysis.
RESULTS: SPD treatment improved coronary BK channel-dependent vasorelaxation by up-regulating BK-β1 subunit expression. Mechanistically, SPD directly bound to pyruvate kinase M2 (PKM2), inhibiting PKM2 nuclear translocation and subsequent signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, STAT3 transcriptionally regulated F-box protein 32 (FBXO32), which modulated BK-β1 expression.
CONCLUSIONS: SPD protects BK channel function in diabetic conditions through inhibition of the PKM2/STAT3 signaling axis, revealing a novel therapeutic pathway for diabetic vascular complications. However, given the exploratory experimental nature of this study, these findings should be considered hypothesis-generating and require further validation in independent studies.
Предметные рубрики MeSH
AnimalsSTAT3 Transcription FactorSignal TransductionCoronary VesselsMyocytes, Smooth MuscleMaleSpermidineMuscle, Smooth, VascularRats, Sprague-DawleyCells, CulturedVasodilationDiabetes Mellitus, ExperimentalLarge-Conductance Calcium-Activated Potassium Channel beta SubunitsRatsPyruvate KinaseVasodilator AgentsDiabetic AngiopathiesLarge-Conductance Calcium-Activated Potassium Channel alpha Subunits