期刊
JOURNAL OF MEDICINAL FOOD
卷 21, 期 2, 页码 146-153出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/jmf.2017.4052
关键词
AMPK; MLCK; p-MLC; quercetin; vasorelaxation; VSMC
资金
- Medical Research Center Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [2015R1A5A2009124]
- National Research Foundation of Korea [2015R1A5A2009124] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 1 and AMPK DN 2-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.
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