Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.
Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.
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DOI：
10.1111/jcmm.12894
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发表时间：
2016-11
影响因子：
5.3
通讯作者：
Brum PC
中科院分区：
文献类型：
--
作者：
Bozi LH;Jannig PR;Rolim N;Voltarelli VA;Dourado PM;Wisløff U;Brum PC
心脏内质网(ER)应激通过错误折叠蛋白的积累在心血管疾病中起着关键作用。为了重建内质网稳态，未折叠蛋白反应(UPR)被激活。然而，如果内质网应激持续存在，持续的UPR激活会导致细胞凋亡。目前还没有有效的治疗方法来缓解ER压力。有氧运动训练(AET)可减轻氧化应激、线粒体功能障碍和钙失衡，可能是一种重建心脏内质网稳态的潜在策略。我们验证了AET可以减轻心肌梗死(MI)后受损的心脏内质网应激的假设。Wistar大鼠接受心肌梗死或假手术。四周后，大鼠接受8周的中等强度的AET。心肌梗死大鼠表现为心功能障碍和肺水肿，提示心力衰竭。心肌梗死大鼠的心功能障碍与UPR标志物(GRP78、Derlin-1和CHOP)的蛋白水平升高、错误折叠和多泛素化蛋白的积累以及类糜凝乳蛋白酶样蛋白酶体活性降低是平行的。这些结果表明心脏蛋白质量控制受损。有氧运动训练提高了心肌梗死动物的运动能力和心功能。有趣的是，AET通过降低UPR标记物的蛋白水平以及错误折叠和多泛素蛋白的积累来钝化MI诱导的内质网应激，这与恢复蛋白酶体活性有关。综上所述，我们的研究为AET通过重建心脏蛋白质量控制来减轻ER应激提供了证据，这有助于改善MI后心力衰竭大鼠的心功能。这些结果加强了AET作为心血管疾病主要非药物治疗的重要性。
Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate‐intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN‐1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin‐like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI‐induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post‐MI heart failure rats. These results reinforce the importance of AET as primary non‐pharmacological therapy to cardiovascular disease.
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内质网相关降解和新型内质网应激反应基因derlin-3的作用。
影响因子：
20.1
作者：
Belmont PJ;Chen WJ;San Pedro MN;Thuerauf DJ;Gellings Lowe N;Gude N;Hilton B;Wolkowicz R;Sussman MA;Glembotski CC
通讯作者：
Glembotski CC
DOI：
10.1152/ajpregu.00424.2007
发表时间：
2008-01-01
影响因子：
2.8
作者：
Ferreira, J. C. B.;Bacurau, A. V.;Brum, P. C.
通讯作者：
Brum, P. C.
DOI：
10.1249/mss.0b013e3180cc25c7
发表时间：
2007-09-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Murlasits, Zsolt;Lee, Youngil;Powers, Scott K.
通讯作者：
Powers, Scott K.
运动训练恢复心力衰竭中心力衰竭的心脏蛋白质质量控制。
影响因子：
3.7
作者：
Campos JC;Queliconi BB;Dourado PM;Cunha TF;Zambelli VO;Bechara LR;Kowaltowski AJ;Brum PC;Mochly-Rosen D;Ferreira JC
通讯作者：
Ferreira JC
影响因子：
5.5
作者：
Oliveira, R. S. F.;Ferreira, J. C. B.;Brum, P. C.
通讯作者：
Brum, P. C.