Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats
Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats
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DOI：
10.1152/japplphysiol.00182.2016
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发表时间：
2017-04-01
影响因子：
3.3
通讯作者：
Brum, Patricia C.
中科院分区：
文献类型：
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作者：
Cunha, Telma F.;Bechara, Luiz R. G.;Brum, Patricia C.
我们最近发现，NADPH氧化酶活性过高、NF-κ B活化和p38磷酸化增加导致心力衰竭（HF）时糖酵解肌萎缩。有氧运动训练（AET）是对抗骨骼肌萎缩的有效策略。因此，我们测试AET是否会调节肌肉氧化还原平衡和蛋白质降解，通过降低NADPH氧化酶的高活性和重建NF-κ B B信号，p38磷酸化和蛋白酶体活性在心肌梗死诱导的HF（MI）大鼠的跖肌。32只雄性Wistar大鼠接受MI或假手术（SHAM），并随机分为未训练（UNT）和训练（T; 8周的AET在跑步机上）组。AET可抑制MI-T大鼠的HF信号和骨骼肌萎缩，提高运动耐量，减轻心功能不全，增加跖肌纤维横截面积。为了验证炎症和氧化还原失衡在触发蛋白质降解中的作用，评估了循环TNF-α水平、NADPH氧化酶谱、NF-κ B信号传导、p38蛋白水平和蛋白酶体活性。MI-T显示TNF-α水平、NADPH氧化酶活性和Nox 2 mRNA表达降低至SHAM-UNT水平。AET通过降低NF-κ B B的核结合活性、p38磷酸化、atrogin-1 mRNA水平和26 S糜蛋白酶样蛋白酶体活性来挽救MI大鼠中由AET诱导的NADPH氧化酶活性。综上所述，我们的数据提供了证据，AET改善与减少NADPH氧化酶，氧化还原敏感蛋白的激活，并进一步防止萎缩的蛋白酶体过度活跃的HF足底氧化还原稳态。这些数据加强了AET的作用，作为一种有效的治疗肌肉萎缩的HF。新&值得注意的是这项研究表明，第一次，有氧运动训练（AET）在减少肌肉NADPH氧化酶活性与减少活性氧产生和全身炎症，减少NF-κ B B过度激活，p38磷酸化，泛素蛋白酶体系统的过度活跃。这些分子变化抵消了训练心肌梗死诱导的心力衰竭大鼠的跖肌萎缩。我们的数据为AET如何调节蛋白质降解从而预防骨骼肌萎缩提供了新的证据。
We have recently demonstrated that NADPH oxidase hyperactivity, NF-kappa B activation, and increased p38 phosphorylation lead to atrophy of glycolytic muscle in heart failure (HF). Aerobic exercise training (AET) is an efficient strategy to counteract skeletal muscle atrophy in this syndrome. Therefore, we tested whether AET would regulate muscle redox balance and protein degradation by decreasing NADPH oxidase hyperactivity and reestablishing NF-kappa B signaling, p38 phosphorylation, and proteasome activity in plantaris muscle of myocardial infarcted-induced HF (MI) rats. Thirty-two male Wistar rats underwent MI or fictitious surgery (SHAM) and were randomly assigned into untrained (UNT) and trained (T; 8 wk of AET on treadmill) groups. AET prevented HF signals and skeletal muscle atrophy in MI-T, which showed an improved exercise tolerance, attenuated cardiac dysfunction and increased plantaris fiber cross-sectional area. To verify the role of inflammation and redox imbalance in triggering protein degradation, circulating TNF-alpha levels, NADPH oxidase profile, NF-kappa B signaling, p38 protein levels, and proteasome activity were assessed. MI-T showed a reduced TNF-alpha levels, NADPH oxidase activity, and Nox2 mRNA expression toward SHAM-UNT levels. The rescue of NADPH oxidase activity induced by AET in MI rats was paralleled by reducing nuclear binding activity of the NF-kappa B, p38 phosphorylation, atrogin-1, mRNA levels, and 26S chymotrypsin-like proteasome activity. Taken together our data provide evidence for AET improving plantaris redox homeostasis in HF associated with a decreased NADPH oxidase, redox-sensitive proteins activation, and proteasome hyperactivity further preventing atrophy. These data reinforce the role of AET as an efficient therapy for muscle wasting in HF.NEW & NOTEWORTHY This study demonstrates, for the first time, the contribution of aerobic exercise training (AET) in decreasing muscle NADPH oxidase activity associated with reduced reactive oxygen species production and systemic inflammation, which diminish NF-kappa B overactivation, p38 phosphorylation, and ubiquitin proteasome system hyperactivity. These molecular changes counteract plantaris atrophy in trained myocardial infarction-induced heart failure rats. Our data provide new evidence into how AET may regulate protein degradation and thus prevent skeletal muscle atrophy.