Exercise Training Prevents TNF-α Induced Loss of Force in the Diaphragm of Mice

Norman Mangner, Axel Linke, Andreas Oberbach, Yvonne Kullnick, Stephan Gielen, Marcus Sandri, Robert Hoellriegel, Yasuharu Matsumoto, Gerhard Schuler, Volker Adams

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31 Citations (Scopus)

Abstract

Rationale: Inflammatory cytokines like tumor necrosis factor alpha (TNF-α) are elevated in congestive heart failure and are known to induce the production of reactive oxygen species as well as to deteriorate respiratory muscle function. Objectives: Given the antioxidative effects of exercise training, the aim of the present study was to investigate if exercise training is capable of preventing a TNF-α induced loss of diaphragmatic force in mice and, if so, to elucidate the potential underlying mechanisms. Methods: Prior to intraperitoneal injection of TNF-α or saline, C57Bl6 mice were assigned to four weeks of exercise training or sedentary behavior. Diaphragmatic force and power generation were determined in vitro. Expression/activity of radical scavenger enzymes, enzymes producing reactive oxygen species and marker of oxidative stress were measured in the diaphragm. Main Results: In sedentary animals, TNF-α reduced specific force development by 42% concomitant with a 2.6-fold increase in the amount of carbonylated α-actin and creatine kinase. Furthermore, TNF-α led to an increased NAD(P)H oxidase activity in both sedentary and exercised mice whereas xanthine oxidase activity and intramitochondrial ROS production was only enhanced in sedentary animals by TNF-α. Exercise training prevented the TNF-α induced force reduction and led to an enhanced mRNA expression and activity of glutathione peroxidase. Carbonylation of proteins, in particular of α-actin and creatine kinase, was diminished by exercise training. Conclusion: TNF-α reduces the force development in the diaphragm of mice. This effect is almost abolished by exercise training. This may be a result of reduced carbonylation of proteins due to the antioxidative properties of exercise training.

Original languageEnglish
Article numbere52274
JournalPloS one
Volume8
Issue number1
DOIs
Publication statusPublished - 2013 Jan 2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Mangner, N., Linke, A., Oberbach, A., Kullnick, Y., Gielen, S., Sandri, M., Hoellriegel, R., Matsumoto, Y., Schuler, G., & Adams, V. (2013). Exercise Training Prevents TNF-α Induced Loss of Force in the Diaphragm of Mice. PloS one, 8(1), [e52274]. https://doi.org/10.1371/journal.pone.0052274