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Quercetin-Induced AMP-Activated Protein Kinase Activation Attenuates Vasoconstriction Through LKB1-AMPK Signaling Pathway

Journal of Medicinal Food 2018년 21권 2호 p.146 ~ 153
Kim Seul-Gi, 김재룡, 최형철,
소속 상세정보
 ( Kim Seul-Gi ) - Yeungnam University College of Medicine Department of Pharmacology
김재룡 ( Kim Jae-Ryong ) - Yeungnam University College of Medicine Department of Biochemistry and Molecular Biology
최형철 ( Choi Hyoung-Chul ) - Yeungnam University College of Medicine Department of Pharmacology

Abstract


The vascular tone plays an important role in blood pressure and flow. It is influenced by the contraction of vascular smooth muscle cells (VSMCs), which in turn is regulated by the balance between the myosin light chain kinase (MLCK) and the phosphorylated myosin light chain (p-MLC). Quercetin is a common flavonoid which is found in many fruits and red wine. Although quercetin has been widely reported to be involved in cell proliferation, migration, and apoptosis in VSMCs, it has not yet been demonstrated whether quercetin is related to vasocontraction, a function regulated by the AMP-activated protein kinase (AMPK) signaling pathway. Accordingly, the aim of this study is to investigate the molecular mechanism through which the quercetin-activated LKB1-AMPK signaling pathway regulates the contraction of VSMCs. In cultured VSMCs, quercetin activated AMPK in a dose- and time-dependent manner. Quercetin inhibited the phenylephrine (PE)-induced expression of MLCK and p-MLC through the LKB1-AMPK signaling pathway and decreased the mRNA level of MLCK. Adenovirus-AMPK DN α1 and AMPK DN α2-transduced VSMCs displayed higher p-MLC expression. Moreover, quercetin inhibited the PE-mediated contraction in rat aorta. These data suggest that the quercetin-activated LKB1-AMPK signaling pathway regulates VSMC contraction by inhibiting MLCK and p-MLC; hence, it may be a therapeutic intervention for the treatment of cardiovascular disorders such as atherosclerosis and hypertension.

키워드

AMPK; MLCK; p-MLC; quercetin; vasorelaxation; VSMC

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