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Proteomic responses of skeletal and cardiac muscle to exercise.

ABSTRACT: Regular exercise is effective in the prevention of chronic diseases and confers a lower risk of death in individuals displaying risk factors such as hypertension and dyslipidemia. Thus, knowledge of the molecular responses to exercise provides a valuable contrast for interpreting investigations of disease and can highlight novel therapeutic targets. While exercise is an everyday experience and can be conceptualized in simple terms, it is also a complex physiological phenomenon and investigation of exercise responses requires sophisticated analytical techniques and careful standardization of the exercise stimulus. Proteomic investigation of exercise is in its infancy but the ability to link changes in function with comprehensive changes in protein expression and post-translational modification holds great promise for advancing physiology. This article highlights recent pioneering work investigating the effects of exercise in skeletal and cardiac muscle that has uncovered novel mechanisms underlying the benefits of physical activity.

SUBMITTER: Burniston JG

PROVIDER: S-EPMC4948674 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Proteomic responses of skeletal and cardiac muscle to exercise.

Burniston Jatin G JG Hoffman Eric P EP

Expert review of proteomics 20110601 3

Regular exercise is effective in the prevention of chronic diseases and confers a lower risk of death in individuals displaying risk factors such as hypertension and dyslipidemia. Thus, knowledge of the molecular responses to exercise provides a valuable contrast for interpreting investigations of disease and can highlight novel therapeutic targets. While exercise is an everyday experience and can be conceptualized in simple terms, it is also a complex physiological phenomenon and investigation ...[more]

PMID: 21679117

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Project description:ObjectiveThe immediate signals that couple exercise to metabolic adaptations are incompletely understood. Nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) produces reactive oxygen species (ROS) and plays a significant role in metabolic and vascular adaptation during stress conditions. Our objective was to determine the role of Nox4 in exercise-induced skeletal muscle metabolism.MethodsMice were subjected to acute exercise to assess their immediate responses. mRNA and protein expression responses to Nox4 and hydrogen peroxide (H2O2) were measured by qPCR and immunoblotting. Functional metabolic flux was measured via ex vivo fatty acid and glucose oxidation assays using 14C-labeled palmitate and glucose, respectively. A chronic exercise regimen was also utilized and the time to exhaustion along with key markers of exercise adaptation (skeletal muscle citrate synthase and beta-hydroxyacyl-coA-dehydrogenase activity) were measured. Endothelial-specific Nox4-deficient mice were then subjected to the same acute exercise regimen and their subsequent substrate oxidation was measured.ResultsWe identified key exercise-responsive metabolic genes that depend on H2O2 and Nox4 using catalase and Nox4-deficient mice. Nox4 was required for the expression of uncoupling protein 3 (Ucp3), hexokinase 2 (Hk2), and pyruvate dehydrogenase kinase 4 (Pdk4), but not the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α). Global Nox4 deletion resulted in decreased UCP3 protein expression and impaired glucose and fatty acid oxidization in response to acute exercise. Furthermore, Nox4-deficient mice demonstrated impaired adaptation to chronic exercise as measured by the time to exhaustion and activity of skeletal muscle citrate synthase and beta-hydroxyacyl-coA-dehydrogenase. Importantly, mice deficient in endothelial-Nox4 similarly demonstrated attenuated glucose and fatty acid oxidation following acute exercise.ConclusionsWe report that H2O2 and Nox4 promote immediate responses to exercise in skeletal muscle. Glucose and fatty acid oxidation were blunted in the Nox4-deficient mice post-exercise, potentially through regulation of UCP3 expression. Our data demonstrate that endothelial-Nox4 is required for glucose and fatty acid oxidation, suggesting inter-tissue cross-talk between the endothelium and skeletal muscle in response to exercise.

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Proteomic responses of skeletal and cardiac muscle to exercise.

Publications

Proteomic responses of skeletal and cardiac muscle to exercise.

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