不同运动训练后肌源性调节因子去甲基化与mRNA表达的相互关联但非时间同步的反应
Interrelated but Not Time-Aligned Response in Myogenic Regulatory Factors Demethylation and mRNA Expression after Divergent Exercise Bouts.
作者信息
Telles Guilherme Defante, Libardi Cleiton Augusto, Conceição Miguel Soares, Vechin Felipe Cassaro, Lixandrão Manoel Emílio, Mangone Flavia Regina Rotea, Pavanelli Ana Carolina, Nagai Maria Aparecida, Camera Donny Michael, Hawley John A, Ugrinowitsch Carlos
机构信息
Laboratory of Neuromuscular Adaptations to Strength Training, School of Physical Education and Sport, University of São Paulo, São Paulo, São Paulo, BRAZIL.
MUSCULAB-Laboratory of Neuromuscular Adaptations to Resistance Training, Department of Physical Education, Federal University of São Carlos, São Carlos, São Paulo, BRAZIL.
出版信息
Med Sci Sports Exerc. 2023 Feb 1;55(2):199-208. doi: 10.1249/MSS.0000000000003049. Epub 2022 Sep 22.
INTRODUCTION
DNA methylation regulates exercise-induced changes in the skeletal muscle transcriptome. However, the specificity and the time course responses in the myogenic regulatory factors DNA methylation and mRNA expression after divergent exercise modes are unknown.
PURPOSE
This study aimed to compare the time course changes in DNA methylation and mRNA expression for selected myogenic regulatory factors ( MYOD1 , MYF5 , and MYF6 ) immediately after, 4 h after, and 8 h after a single bout of resistance exercise (RE), high-intensity interval exercise (HIIE), and concurrent exercise (CE).
METHODS
Nine healthy but untrained males (age, 23.9 ± 2.8 yr; body mass, 70.1 ± 14.9 kg; peak oxygen uptake [V̇O 2peak ], 41.4 ± 5.2 mL·kg -1 ·min -1 ; mean ± SD) performed a counterbalanced, randomized order of RE (4 × 8-12 repetition maximum), HIIE (12 × 1 min sprints at V̇O 2peak running velocity), and CE (RE followed by HIIE). Skeletal muscle biopsies (vastus lateralis) were taken before (REST) immediately (0 h), 4 h, and 8 h after each exercise bout.
RESULTS
Compared with REST, MYOD1 , MYF5 , and MYF6 , mean methylation across all CpGs analyzed was reduced after 4 and 8 h in response to all exercise protocols ( P < 0.05). Reduced levels of MYOD1 methylation were observed after HIIE and CE compared with RE ( P < 0.05). Compared with REST, all exercise bouts increased mRNA expression over time ( MYOD1 at 4 and 8 h, and MYF6 at 4 h; P < 0.05). MYF5 mRNA expression was lower after 4 h compared with 0 h and higher at 8 h compared with 4 h ( P < 0.05).
CONCLUSIONS
We observed an interrelated but not time-aligned response between the exercise-induced changes in myogenic regulatory factors demethylation and mRNA expression after divergent exercise modes. Despite divergent contractile stimuli, changes in DNA methylation and mRNA expression in skeletal muscle were largely confined to the late (4-8 h) recovery period and similar between the different exercise challenges.
引言
DNA甲基化调节运动诱导的骨骼肌转录组变化。然而，不同运动模式后肌源性调节因子的DNA甲基化和mRNA表达的特异性及时间进程反应尚不清楚。
目的
本研究旨在比较单次阻力运动（RE）、高强度间歇运动（HIIE）和联合运动（CE）后即刻、4小时后和8小时后，所选肌源性调节因子（MYOD1、MYF5和MYF6）的DNA甲基化和mRNA表达的时间进程变化。
方法
9名健康但未受过训练的男性（年龄，23.9±2.8岁；体重，70.1±14.9千克；峰值摄氧量[V̇O₂peak]，41.4±5.2毫升·千克⁻¹·分钟⁻¹；平均值±标准差）按照平衡、随机的顺序进行RE（4组，每组8 - 12次最大重复量）、HIIE（以V̇O₂peak跑步速度进行12次1分钟冲刺）和CE（先进行RE，随后进行HIIE）。在每次运动前（静息状态）、运动后即刻（0小时）、4小时和8小时采集骨骼肌活检样本（股外侧肌）。
结果
与静息状态相比，所有运动方案后4小时和8小时，所分析的所有CpG位点上MYOD1、MYF5和MYF6的平均甲基化水平均降低（P<0.05）。与RE相比，HIIE和CE后观察到MYOD1甲基化水平降低（P<0.05）。与静息状态相比，所有运动方案随时间推移均增加了mRNA表达（4小时和8小时时的MYOD1，以及4小时时的MYF6；P<0.05）。与0小时相比，4小时时MYF5的mRNA表达较低，与4小时相比，8小时时较高（P<0.05）。
结论
我们观察到不同运动模式后，运动诱导的肌源性调节因子去甲基化和mRNA表达变化之间存在相互关联但不同步的反应。尽管收缩刺激不同，但骨骼肌中DNA甲基化和mRNA表达的变化主要局限于后期（4 - 8小时）恢复期，且在不同运动挑战之间相似。
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