Mediators of Physical Activity Protection against ROS-Linked Skeletal Muscle Damage

Int J Mol Sci. 2019 Jun 20;20(12):3024. doi: 10.3390/ijms20123024.

Abstract

Unaccustomed and/or exhaustive exercise generates excessive free radicals and reactive oxygen and nitrogen species leading to muscle oxidative stress-related damage and impaired contractility. Conversely, a moderate level of free radicals induces the body's adaptive responses. Thus, a low oxidant level in resting muscle is essential for normal force production, and the production of oxidants during each session of physical training increases the body's antioxidant defenses. Mitochondria, NADPH oxidases and xanthine oxidases have been identified as sources of free radicals during muscle contraction, but the exact mechanisms underlying exercise-induced harmful or beneficial effects yet remain elusive. However, it is clear that redox signaling influences numerous transcriptional activators, which regulate the expression of genes involved in changes in muscle phenotype. The mitogen-activated protein kinase family is one of the main links between cellular oxidant levels and skeletal muscle adaptation. The family components phosphorylate and modulate the activities of hundreds of substrates, including transcription factors involved in cell response to oxidative stress elicited by exercise in skeletal muscle. To elucidate the complex role of ROS in exercise, here we reviewed the literature dealing on sources of ROS production and concerning the most important redox signaling pathways, including MAPKs that are involved in the responses to acute and chronic exercise in the muscle, particularly those involved in the induction of antioxidant enzymes.

Keywords: Nrf2; PGC-1; UCPs; cancer; cardiovascular disease; exercise; insulin resistance; mitochondria; neurodegenerative disorders; oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Exercise*
  • Humans
  • MAP Kinase Signaling System
  • Mitochondria / metabolism
  • Muscle Fatigue
  • Muscle, Skeletal / physiology*
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*

Substances

  • Reactive Oxygen Species