Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction.
Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction.
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肌肉特异性组蛋白甲基转移酶 (Smyd1) 在运动诱导的心肌保护作用中对心肌梗死后病理重塑的作用
DOI：
10.3390/ijms21197010
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发表时间：
2020-09-23
影响因子：
5.6
通讯作者：
Tian Z
中科院分区：
文献类型：
--
作者：
Liang Q;Cai M;Zhang J;Song W;Zhu W;Xi L;Tian Z
病理性重构是心肌梗死后的主要并发症。梗死心肌中活性氧（ROS）的过度产生可能有助于这一过程。MI后适当的运动训练可以减少氧化应激诱导的心脏组织损伤和重塑。SET and MYND domain containing 1（Smyd 1）是一种肌肉特异性组蛋白甲基转移酶，其通过阻力训练上调，可以加强肌节组装和肌纤维折叠，并且可以促进骨骼肌生长和肥大。然而，Smyd 1是否在MI后心肌中具有类似的功能并参与运动诱导的心脏保护仍然是未知的。因此，我们研究了间歇跑台运动对正常和梗死心脏的心功能、ROS生成、Smyd 1表达和F-肌动蛋白肌节组装的影响。将成年雄性大鼠随机分为5组（n = 10/组）：对照组（C）、单纯运动组（EX）、假手术组（S）、永久结扎冠状动脉左前降支（MI）组和MI+间歇运动组（MI + EX）。运动训练显著改善心肌梗死后心功能和肌节组装的F-肌动蛋白。心肌保护作用与Smyd 1、Trx 1、cTnI和α-辅肌动蛋白表达增加以及磷酸化AMP活化蛋白激酶（AMPK）/AMPK比值上调有关，而Hsp 90、MuRF 1、脑钠肽（BNP）表达、ROS生成和心肌纤维化则减弱。MI后心功能的改善与Smyd 1表达的增加相关。在体外培养的H9 C2心肌细胞中，用H2 O2（50 μmol/L）或AMP活化蛋白激酶（AMPK）激动剂（AICAR，1 mmol/L）或其组合处理4 h模拟运动对ROS和Smyd 1水平的影响。总之，我们证明了Smyd 1与心肌梗死后运动诱导的心脏保护相关的新作用。ROS诱导的Smyd 1的适度上调可能是调节MI后心脏功能和重塑的重要靶点。
Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups (n = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with H2O2 (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.
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DOI：
10.1016/j.bbapap.2015.09.006
发表时间：
2015-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Liu T;Wu C;Jain MR;Nagarajan N;Yan L;Dai H;Cui C;Baykal A;Pan S;Ago T;Sadoshima J;Li H
通讯作者：
Li H
影响因子：
4
作者：
Just, Steffen;Meder, Benjamin;Rottbauer, Wolfgang
通讯作者：
Rottbauer, Wolfgang
影响因子：
3.9
作者：
Cheng Y;Regnier M
通讯作者：
Regnier M
影响因子：
2.5
作者：
Helgerud, J.;Karlsen, T.;Hoff, J.
通讯作者：
Hoff, J.
DOI：
10.1152/ajpheart.1999.277.5.h2026
发表时间：
1999-11-01
影响因子：
4.8
作者：
Baliga, RR;Pimental, DR;Kelly, RA
通讯作者：
Kelly, RA