Department of Kinesiology, McMaster University, Hamilton, Ontario, CANADA.
Med Sci Sports Exerc. 2018 Mar;50(3):447-457. doi: 10.1249/MSS.0000000000001476.
This study aimed to determine protein arginine methyltransferase 1 (PRMT1), -4 (also known as coactivator-associated arginine methyltransferase 1 [CARM1]), and -5 expression and function during acute, exercise-induced skeletal muscle remodeling in vivo.
C57BL/6 mice were assigned to one of three experimental groups: sedentary, acute bout of exercise, or acute exercise followed by 3 h of recovery. Mice in the exercise groups performed a single bout of treadmill running at 15 m·min for 90 min. Hindlimb muscles were collected, and quantitative real-time polymerase chain reaction and Western blotting were used to examine exercise-induced gene expression.
The PRMT gene expression and global enzyme activity were muscle-specific, generally being higher (P < 0.05) in slow, oxidative muscle, as compared with faster, more glycolytic tissue. Despite the significant activation of canonical exercise-induced signaling involving AMP-activated protein kinase and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), PRMT expression and activity at the whole muscle level were unchanged. However, subcellular analyses revealed a significant exercise-evoked myonuclear translocation of PRMT1 before the nuclear accumulation of PGC-1α. Acute physical activity also augmented (P < 0.05) the targeted methyltransferase activities of the PRMT in the myonuclear compartment, suggesting that PRMT-mediated histone arginine methylation is part of the early signals that drive muscle plasticity. Finally, basal PGC-1α asymmetric dimethylarginine status, as well as constitutive interactions between PGC-1α and PRMT1 or CARM1 may contribute to the exercise-induced muscle remodeling process.
The present study provides the first evidence that PRMT activity is selectively augmented during the initial activation of exercise-induced skeletal muscle remodeling in vivo. These data support the emergence of PRMTs as important players in the regulation of skeletal muscle plasticity.
本研究旨在确定精氨酸甲基转移酶 1（PRMT1）、-4（也称为共激活因子相关的精氨酸甲基转移酶 1 [CARM1]）和-5 在体内急性运动诱导的骨骼肌重塑过程中的表达和功能。
将 C57BL/6 小鼠分为三组：安静组、急性运动组或急性运动后 3 小时恢复组。运动组的小鼠在跑步机上以 15 m·min 的速度跑 90 分钟。采集后肢肌肉，采用实时定量聚合酶链反应和 Western 印迹法检测运动诱导的基因表达。
PRMT 基因表达和整体酶活性具有肌肉特异性，与更快、更糖酵解的组织相比，通常在慢、氧化肌肉中更高（P < 0.05）。尽管经典的运动诱导信号通路（涉及 AMP 激活蛋白激酶和过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α））被显著激活，但整个肌肉水平的 PRMT 表达和活性没有变化。然而，亚细胞分析显示，在 PGC-1α 核积累之前，PRMT1 发生了显著的运动诱发的核内易位。急性体力活动也增加了（P < 0.05）核内 PRMT 的靶向甲基转移酶活性，这表明 PRMT 介导的组蛋白精氨酸甲基化是驱动肌肉可塑性的早期信号的一部分。最后，PGC-1α 的基础不对称二甲基精氨酸状态以及 PGC-1α 与 PRMT1 或 CARM1 之间的组成性相互作用可能有助于运动诱导的肌肉重塑过程。
本研究首次提供了证据表明，PRMT 活性在体内急性运动诱导的骨骼肌重塑的初始激活过程中被选择性增强。这些数据支持 PRMTs 作为调节骨骼肌可塑性的重要因子的出现。
