Exercise training restores cardiac protein quality control in heart failure.
Exercise training restores cardiac protein quality control in heart failure.
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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。
DOI：
10.1371/journal.pone.0052764
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ferreira JC
中科院分区：
文献类型：
--
作者：
Campos JC;Queliconi BB;Dourado PM;Cunha TF;Zambelli VO;Bechara LR;Kowaltowski AJ;Brum PC;Mochly-Rosen D;Ferreira JC
运动训练是一种众所周知的辅助治疗心力衰竭;然而，其有益作用的分子机制仍然难以捉摸。尽管是主要原因，但心力衰竭之前通常有两种不同的现象：线粒体功能障碍和细胞溶质蛋白质质量控制中断。本研究的目的是确定运动训练在心肌梗死后诱导的心力衰竭（MI-HF）动物模型中调节心肌线粒体代谢和细胞溶质蛋白质质量控制的贡献。我们的数据表明，从MI-HF大鼠中分离的心脏线粒体显示出耗氧量减少、最大钙吸收减少和H2 O2释放增加。这些变化伴随着心脏氧化应激和蛋白酶体功能不全的加剧。在我们的MI-HF模型中，蛋白酶体活性下降导致心脏蛋白质质量控制中断。使用培养的新生心肌细胞，我们表明，无论是抗霉素A或过氧化氢导致蛋白酶体肽酶活性的失活，氧化蛋白的积累和细胞死亡，重演我们在体内模型。有趣的是，八周的运动训练改善了MI-HF大鼠的心脏功能、峰值摄氧量和运动耐量。此外，运动训练恢复线粒体耗氧量，增加Ca 2+诱导的通透性转换和减少H2 O2释放MI-HF大鼠。这些变化之后，氧化应激减少，心脏蛋白质质量控制更好。总之，我们的研究结果揭示了线粒体功能障碍和细胞溶质蛋白质质量控制中断对心力衰竭的潜在贡献，并强调了运动训练在重建心脏线粒体生理学和蛋白质质量控制方面的积极作用，加强了这种干预作为心力衰竭治疗非药物工具的重要性。
Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF) animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H2O2 release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H2O2 resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca2+-induced permeability transition and reduced H2O2 release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a non-pharmacological tool for heart failure therapy.
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影响因子：
6.1
作者：
Ferreira, Julio C. B.;Moreira, Jose B. N.;Brum, Patricia C.
通讯作者：
Brum, Patricia C.
DOI：
10.1152/ajpheart.00526.2005
发表时间：
2005-11-01
影响因子：
4.8
作者：
Emter, CA;McCune, SA;Moore, RL
通讯作者：
Moore, RL
影响因子：
25
作者：
Antony, JM;van Marle, G;Power, C
通讯作者：
Power, C
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.
影响因子：
11.4
作者：
Liberek, Krzysztof;Lewandowska, Agnieszka;Zietkiewicz, Szymon
通讯作者：
Zietkiewicz, Szymon