The green tea polyphenol epigallocatechin-3-gallate attenuates age-associated muscle loss via regulation of miR-486-5p and myostatin
The green tea polyphenol epigallocatechin-3-gallate attenuates age-associated muscle loss via regulation of miR-486-5p and myostatin
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DOI：
10.1016/j.abb.2020.108511
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发表时间：
2020-10-15
影响因子：
3.9
通讯作者：
Chang, Sue-Joan
中科院分区：
文献类型：
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作者：
Chang, Yun-Ching;Liu, Hung-Wen;Chang, Sue-Joan
（-）-表没食子儿茶素没食子酸酯（EGCG）是绿色茶中含量最丰富的儿茶素成分，在我们以前和现在的研究中，已经报道通过恢复骨骼肌中Akt的活性来减轻与年龄相关的胰岛素抵抗、脂肪生成和肌肉质量损失。累积的数据表明，多酚通过调节miRNA表达来调节衰老过程中涉及的信号通路，如炎症和氧化应激。在这里，我们发现miRNA-486- 5 p在衰老加速小鼠易感8（SAMP 8）小鼠和晚代C2 C12细胞中均显著降低。因此，我们进一步研究了EGCG对年龄调节的肌肉损失中miRNA-486- 5 p表达的调节作用。从32周龄开始用不含或含0.32%EGCG的普通饲料喂养SAMP 8小鼠8周。C2 C12细胞的早期传代（12代）和晚期传代（30代）不加或加浓度为50 μ M的EGCG处理24小时。我们的数据显示，补充EGCG增加了老年SAMP 8小鼠和晚期传代C2 C12细胞中miRNA-486- 5 p的表达。EGCG通过上调40周龄SAMP 8小鼠骨骼肌和晚期传代C2 C12细胞中miR-486的表达，刺激AKT磷酸化，抑制FoxO 1介导的MuRF 1和Atrogin-1转录。此外，肌生长抑制素表达在晚期传代C2 C12细胞中增加，并且抗肌生长抑制素处理上调miR-486- 5 p的表达。我们的研究结果确定了绿色茶的膳食成分的独特机制，并表明使用EGCG或其衍生的化合物通过肌生长抑制素/miRNA/泛素-蛋白酶体信号传导减弱与年龄相关的肌肉损失。
(-)-Epigallocatechin-3-gallate (EGCG), the most abundant catechin component in green tea, has been reported to attenuate age-associated insulin resistance, lipogenesis and loss of muscle mass through restoring Akt activity in skeletal muscle in our previous and present studies. Accumulated data has suggested that polyphenols regulate signaling pathways involved in aging process such as inflammation and oxidative stress via modulation of miRNA expression. Here we found that miRNA-486-5p was significantly decreased in both aged senescence accelerated mouse-prone 8 (SAMP8) mice and late passage C2C12 cells. Thus, we further investigated the regulatory effect of EGCG on miRNA-486-5p expression in age-regulated muscle loss. SAMP8 mice were fed with chow diet containing without or with 0.32% EGCG from aged 32 weeks for 8 weeks. Early passage (12 passages) and late passage (30 passages) of C2C12 cells were treated without or with EGCG at concentrations of 50 mu M for 24h. Our data showed that EGCG supplementation increased miRNA-486-5p expression in both aged SAMP8 mice and late passage C2C12 cells. EGCG stimulated AKT phosphorylation and inhibited FoxO1amediated MuRF1 and Atrogin-1 transcription via up-regulating the expression of miR-486 in skeletal muscle of 40-wk-old SAMP8 mice as well as late passage C2C12 cells. In addition, myostatin expression was increased in late passage C2C12 cells and anti-myostatin treatment upregulated the expression of miR-486-5p. Our results identify a unique mechanism of a dietary constituent of green tea and suggest that use of EGCG or compounds derived from it attenuates age-associated muscle loss via myostatin/miRNAs/ubiquitin-proteasome signaling.