(-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12 myotubes via the G-protein coupled estrogen receptor.
(-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12 myotubes via the G-protein coupled estrogen receptor.
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DOI：
10.1016/j.ejphar.2018.01.014
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发表时间：
2018-03-05
影响因子：
5
通讯作者：
Álvarez-Delgado C
中科院分区：
文献类型：
--
作者：
Moreno-Ulloa A;Miranda-Cervantes A;Licea-Navarro A;Mansour C;Beltrán-Partida E;Donis-Maturano L;Delgado De la Herrán HC;Villarreal F;Álvarez-Delgado C
我们已经报道了（-）-表儿茶素（（-）-EPI）刺激小鼠骨骼肌（SkM）线粒体生物合成（MiB）的能力。然而，介导（-）-EPI作用的机制尚未完全了解。我们以前确定了G蛋白偶联雌激素受体（GPER）在调节（−）-EPI的血管效应中的作用。因此，我们检验了GPER介导（至少部分）（-）-EPI对SkM细胞中MiB的刺激作用的假设。作为体外模型，我们采用小鼠SkM衍生的C2 C12成肌细胞分化成肌管。利用共聚焦显微镜，我们检测GPER在细胞表面和细胞质中的C2 C12肌管。用（-）-EPI（3和10 μM）处理导致MiB的刺激，其表现为线粒体内膜（MitoTracker Red FM荧光染色）和外膜（孔蛋白水平）标记物、参与MiB刺激的转录因子（即，核呼吸因子-2（NRF-2）和线粒体转录因子A（TFAM）蛋白水平）和柠檬酸合酶（CS）活性水平。（-）-EPI处理的肌管比赋形剂处理的肌管更长更宽。（−）-EPI对肌管线粒体和细胞大小的影响在幅度上大于GPER激动剂G-1。GPER的化学阻断和下调（siRNA）分别证明了（−）-EPI-或G-1-治疗后测量终点的部分和完全阻断。总之，结果表明GPER在肌肉细胞中表达，并且似乎在很大程度上介导（-）-EPI对MiB的刺激作用。因此，GPER激活可能解释了（-）-EPI对SkM结构/功能的刺激作用。
We have reported on the capacity of (−)-epicatechin ((−)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (−)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (−)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (−)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes. Using confocal microscopy, we detected GPER at the cell surface and cytoplasm in C2C12 myotubes. Treatment with (−)-EPI (3 and 10 µM) resulted in the stimulation of MiB as per increases in mitochondrial inner (MitoTracker Red FM fluorescence staining) and outer membrane (porin protein levels) markers, transcription factors involved in MiB stimulation (i.e., nuclear respiratory factor-2 [NRF-2] and mitochondrial transcription factor A [TFAM] protein levels) and citrate synthase (CS) activity levels. (−)-EPI-treated myotubes were longer and wider compared to vehicle-treated myotubes. The effects of (−)-EPI on myotube mitochondria and cell size were larger in magnitude to those observed with the GPER agonist G-1. The chemical blockade and down-regulation (siRNA) of GPER evidenced a partial and complete blockade of measured endpoints following (−)-EPI- or G-1-treatment, respectively. Altogether, results indicate that GPER is expressed in muscle cells and appears to mediate to a significant extent, the stimulatory effects of (−)-EPI on MiB. Thus, GPER activation may account for the stimulatory effects of (−)-EPI on SkM structure/function.
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影响因子：
5.2
作者：
Panneerselvam, Mathivadhani;Ali, Sameh S.;Finley, J. Cameron;Kellerhals, Sarah E.;Migita, Michael Y.;Head, Brian P.;Patel, Piyush M.;Roth, David M.;Patel, Hemal H.
通讯作者：
Patel, Hemal H.
影响因子：
2.7
作者：
Moreno-Ulloa, Aldo;Romero-Perez, Diego;Ramirez-Sanchez, Israel
通讯作者：
Ramirez-Sanchez, Israel
影响因子：
4.8
作者：
Hepple RT
通讯作者：
Hepple RT
影响因子：
4.6
作者：
Meyer MR;Fredette NC;Howard TA;Hu C;Ramesh C;Daniel C;Amann K;Arterburn JB;Barton M;Prossnitz ER
通讯作者：
Prossnitz ER
影响因子：
9.3
作者：
Moreno-Ulloa A;Mendez-Luna D;Beltran-Partida E;Castillo C;Guevara G;Ramirez-Sanchez I;Correa-Basurto J;Ceballos G;Villarreal F
通讯作者：
Villarreal F