Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

被引:61
作者
Campos, Juliane C. [1 ]
Queliconi, Bruno B. [2 ]
Dourado, Paulo M. M. [3 ]
Cunha, Telma F. [4 ]
Zambelli, Vanessa O. [5 ]
Bechara, Luiz R. G. [4 ]
Kowaltowski, Alicia J. [2 ]
Brum, Patricia C. [4 ]
Mochly-Rosen, Daria [6 ]
Ferreira, Julio C. B. [1 ,6 ]
机构
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, Brazil
[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, Brazil
[3] Univ Sao Paulo, Inst Heart, Sao Paulo, Brazil
[4] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil
[5] Butantan Inst, Sao Paulo, Brazil
[6] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA
来源
PLOS ONE | 2012年 / 7卷 / 12期
基金
巴西圣保罗研究基金会;
关键词
UBIQUITIN-PROTEASOME SYSTEM; 20S PROTEASOME; MICE; DYSFUNCTION; MITOCHONDRIA; DEGRADATION; PROGRESSION; ACTIVATION; DEHYDROGENASE; INACTIVATION;
D O I
10.1371/journal.pone.0052764
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 nonpharmacological tool for heart failure therapy.
引用
收藏
页数:12
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