Kim A Rum, Kim Kyung Min, Byun Mi Ran, Hwang Jun-Ha, Park Jung Il, Oh Ho Taek, Jeong Mi Gyeong, Hwang Eun Sook, Hong Jeong-Ho
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea.
College of Pharmacy, Ewha Woman's University, Seoul 03760, South Korea.
Biochem Biophys Res Commun. 2017 Apr 29;486(2):378-384. doi: 10.1016/j.bbrc.2017.03.049. Epub 2017 Mar 14.
Muscle loss is a typical process of aging. Green tea consumption is known to slow down the progress of aging. Their underlying mechanisms, however, remain largely unknown. In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a polyphenolic compound of green tea, on myogenic differentiation and found that EGCG significantly increases myogenic differentiation. After EGCG treatment, the expression of myogenic marker genes, such as myosin heavy chain, are increased through activation of TAZ, a transcriptional coactivator with a PDZ-binding motif. TAZ-knockdown does not stimulate EGCG-induced myogenic differentiation. EGCG facilitates the interaction between TAZ and MyoD, which stimulates MyoD-mediated gene transcription. EGCG induces nuclear localization of TAZ through the dephosphorylation of TAZ at its Ser89 residue, which relieves 14-3-3 binding in the cytosol. Interestingly, inactivation of Lats kinase is observed after EGCG treatment, which is responsible for the production of dephosphorylated TAZ. Together, these results suggest that EGCG induces myogenic differentiation through TAZ, suggesting that TAZ plays an important role in EGCG induced muscle regeneration.
肌肉流失是衰老的一个典型过程。已知饮用绿茶可减缓衰老进程。然而，其潜在机制在很大程度上仍不为人知。在本研究中，我们研究了绿茶中的一种多酚类化合物（-）-表没食子儿茶素-3-没食子酸酯（EGCG）对成肌分化的影响，发现EGCG显著增强成肌分化。EGCG处理后，肌球蛋白重链等成肌标记基因的表达通过激活具有PDZ结合基序的转录共激活因子TAZ而增加。敲低TAZ不会刺激EGCG诱导的成肌分化。EGCG促进TAZ与MyoD之间的相互作用，从而刺激MyoD介导的基因转录。EGCG通过使TAZ的Ser89残基去磷酸化诱导TAZ的核定位，这解除了TAZ在细胞质中与14-3-3的结合。有趣的是，EGCG处理后观察到Lats激酶失活，Lats激酶负责产生去磷酸化的TAZ。总之，这些结果表明EGCG通过TAZ诱导成肌分化，提示TAZ在EGCG诱导的肌肉再生中起重要作用。
