Identification of a Novel Function of Resveratrol and Genistein as a Regulator of β2-Adrenergic Receptor Expression in Skeletal Muscle Cells and Characterization of Promoter Elements Required for Promoter Activation
Identification of a Novel Function of Resveratrol and Genistein as a Regulator of β2-Adrenergic Receptor Expression in Skeletal Muscle Cells and Characterization of Promoter Elements Required for Promoter Activation
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DOI：
10.1002/mnfr.201800530
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发表时间：
2018-11-01
影响因子：
5.2
通讯作者：
Sato, Ryuichiro
中科院分区：
文献类型：
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作者：
Chikazawa, Miho;Sato, Ryuichiro
调节β(2)-肾上腺素能受体(beta(2)-AR)的表达和激活对维持骨骼肌功能具有重要意义。在这项研究中，两种食物因子，白藜芦醇(RSV)和染料木素(GEN)，能够调节β(2)-AR启动子的活性，并可能改善骨骼肌功能。通过荧光素酶报告实验，筛选出357个功能食品因子作为β(2)-AR启动子活性的候选因子，随后RSV和Gen提高了β(2)-AR启动子活性和β(2)-AR mRNA的表达。启动子序列分析表明，RSV或Gen在β(2)-AR启动子上的CCAAT盒和GC盒是调节β(2)-AR表达所必需的。还证实了转录因子NF-YA与β(2)-AR启动子上的CCAAT盒结合，并且通过RSV或Gen处理，与CCAAT盒结合的核因子-YA的量不变。最后，证实了含有Gen的饮食增加了小鼠骨骼肌中β(2)-AR的表达，并增加了骨骼肌质量。结论食源性分子可能通过调节G蛋白偶联受体的表达而影响骨骼肌的质量和功能。
Scope Modulating beta(2)-adrenergic receptor (beta(2)-AR) expression and activation is important for maintaining skeletal muscle function. In this study, two food factors, resveratrol (RSV) and genistein (GEN), that are able to regulate beta(2)-AR promoter activity and may improve skeletal muscle function are identified. Using luciferase reporter assay, 357 functional food factors as candidates for beta(2)-AR promoter activity have been screened and subsequently RSV and GEN increase beta(2)-AR promoter activity and beta(2)-AR mRNA expression. Using promoter sequence analysis, it is shown that the CCAAT box and the GC box on the beta(2)-AR promoter are required for the regulation of beta(2)-AR expression by RSV or GEN. It is also ascertained that transcription factor NF-YA binds to the CCAAT box on the beta(2)-AR promoter and that the amount of NF-YA bound to the CCAAT box is unchanged by RSV or GEN treatment. Finally, it is confirmed that a GEN-containing diet increases beta(2)-AR expression in mouse skeletal muscle and increased skeletal muscle mass. Conclusions The findings show that food-derived molecules have the potential to influence skeletal muscle mass and function by regulating G protein-coupled receptor expression.