Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 7, n. 12 DEC 27 2012.
• Citações Web of Science: 44

Resumo

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. (AU)

• Processo FAPESP: 10/00028-4 - Caracterização dos processos de fusão e fissão de mitocôndria na insuficiência cardíaca: efeitos do treinamento físico aeróbico
• Beneficiário: Patricia Chakur Brum
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/05765-2 - Contribuição da enzima aldeído desidrogenase 2 na progressão da insuficiência cardíaca
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 09/18546-4 - Controle de qualidade de proteína na insuficiência cardíaca: papel das diferentes isoformas de proteína quinase C
• Beneficiário: Patricia Chakur Brum
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/12349-2 - Caracterização da função e da dinâmica mitocondrial em modelo animal de disfunção cardíaca associada ao infarto do miocárdio
• Beneficiário: Juliane Cruz Campos
• Modalidade de apoio: Bolsas no Brasil - Mestrado