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首页> 外文期刊>The Journal of Nutritional Biochemistry >Green tea component EGCG, insulin and IGF-1 promote nuclear efflux of atrophy-associated transcription factor Foxo1 in skeletal muscle fibers
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Green tea component EGCG, insulin and IGF-1 promote nuclear efflux of atrophy-associated transcription factor Foxo1 in skeletal muscle fibers

机译：绿茶成分EGCG，胰岛素和IGF-1促进骨骼肌纤维中萎缩相关转录因子Foxo1的核外排

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摘要

Prevention and slowing of skeletal muscle atrophy with nutritional approaches offers the potential to provide far-reaching improvements in the quality of life for our increasingly aging population. Here we show that polyphenol flavonoid epigallocatechin 3-gallate (EGCG), found in the popular beverage green tea (Camellia sinensis), demonstrates similar effects to the endogenous hormones insulin-like growth factor 1 (IGF-1) and insulin in the ability to suppress action of the atrophy-promoting transcription factor Foxo1 through a net translocation of Foxo1 out of the nucleus as monitored by nucleo-cytoplasmic movement of Foxo1-green fluorescent protein (GFP) in live skeletal muscle fibers. Foxo1-GFP nuclear efflux is rapid in IGF-1 or insulin, but delayed by an additional 30 min for EGCG. Once activated, kinetic analysis with a simple mathematical model shows EGCG, IGF-1 and insulin all produce similar apparent rate constants for Foxo1-GFP unidirectional nuclear influx and efflux. Interestingly, EGCG appears to have its effect at least partially via parallel signaling pathways that are independent of IGF-1's (and insulin's) downstream PI3K/Akt/Foxo1 signaling axis. Using the live fiber model system, we also determine the dose-response curve for both IGF-1 and insulin on Foxo1 nucleo-cytoplasmic distribution. The continued understanding of the activation mechanisms of EGCG could allow for nutritional promotion of green tea's antiatrophy skeletal muscle benefits and have implications in the development of a clinically significant parallel pathway for new drugs to target muscle wasting and the reduced insulin receptor sensitivity which causes type II diabetes mellitus. (C) 2015 Elsevier Inc. All rights reserved.
机译：通过营养方法预防和减缓骨骼肌萎缩，为我们日益老龄化的人口提供了改善生活质量的深远潜力。在这里，我们显示在流行的饮料绿茶（茶树）中发现的多酚类黄酮表没食子儿茶素3-没食子酸酯3-没食子酸酯（EGCG）具有与内源性激素类胰岛素样生长因子1（IGF-1）和胰岛素相似的作用。抑制萎缩促进转录因子Foxo1的作用是通过Foxo1从细胞核中的净移位，如通过活骨骼肌纤维中Foxo1-绿色荧光蛋白（GFP）的核质移动所监测的。 Foxo1-GFP核外排在IGF-1或胰岛素中迅速，但对于EGCG则再延迟30分钟。一旦激活，用简单数学模型进行的动力学分析表明，EGCG，IGF-1和胰岛素对于Foxo1-GFP单向核流入和流出均产生相似的表观速率常数。有趣的是，EGCG似乎至少部分地通过平行于IGF-1（和胰岛素）下游PI3K / Akt / Foxo1信号传导轴的平行信号传导途径发挥作用。使用活纤维模型系统，我们还确定了IGF-1和胰岛素对Foxo1核质分布的剂量反应曲线。对EGCG激活机制的持续理解可能有助于营养促进绿茶抗萎缩性骨骼肌的益处，并且对开发新的靶向肌肉消耗的临床上重要的平行途径和降低引起II型胰岛素受体敏感性的临床意义产生影响糖尿病。 （C）2015 Elsevier Inc.保留所有权利。

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