title: Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats.
abstract: We have recently demonstrated that NADPH oxidase hyperactivity, NF-κB 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-κB 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-α levels, NADPH oxidase profile, NF-κB signaling, p38 protein levels, and proteasome activity were assessed. MI-T showed a reduced TNF-α 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-κB, 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 & NOTEWORTHYThis 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-κB 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.
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Telma F
authors.initials: TF
authors.lastname: Cunha
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Luiz R G
authors.initials: LR
authors.lastname: Bechara
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Aline V N
authors.initials: AV
authors.lastname: Bacurau
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Jannig
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Voltarelli
authors.affiliation: Heart Institute, Faculty of Medicine, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Dourado
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; and.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Vasconcelos
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; and.
authors.forename: Cristóforo
authors.initials: C
authors.lastname: Scavone
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, São Paulo, Brazil.
authors.forename: Júlio C B
authors.initials: JC
authors.lastname: Ferreira
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil; pcbrum@usp.br.
authors.forename: Patricia C
authors.identifier: http://orcid.org/0000-0002-4750-6506
authors.initials: PC
authors.lastname: Brum
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005080:Exercise Test / Q000379:methods; D006321:Heart / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex
keywords: NADPH oxidase; NF-κB; exercise training; heart failure; muscle